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Design and rationale of a study in Asia of atorvastatin pretreatment in patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Impact of gender difference on long-term outcomes of percutaneous coronary intervention for coronary artery disease in patients under statin treatment Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. Early high-dose rosuvastatin and cardioprotection in the protective effect of rosuvastatin and antiplatelet therapy on contrast-induced acute kidney injury and myocardial damage in patients with acute coronary syndrome (PRATO-ACS) study. The effect of Mediterranean diet on the risk of the development of acute coronary syndromes in hypercholesterolemic people: a case–control study (CARDIO2000) The effect of different doses of fluvastatin on inflammatory markers in the early phase of acute coronary syndrome. The influence of low dose atorvastatin on inflammatory marker levels in patients with acute coronary syndrome and its potential clinical value. [The changes of electrocardiogram and impact of early invasive strategy in patients with acute coronary syndromes without ST-segment elevation]. The early glycoprotein IIb/IIIa inhibition in non-ST-segment elevation acute coronary syndrome (EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndro [The relationship between TIMI (thrombolysis in myocardial infarction) risk score and efficacy of conservative or interventional strategy in patients with non-ST-segment elevation acute coronary syndromes]. [The effect of early invasive strategy on early and late outcomes in high-risk non-ST-segment elevation acute coronary syndromes]. 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BACKGROUND The ESTABLISH trial found using volumetric intravascular ultrasound that atorvastatin therapy started early and continued for 6 months significantly reduced plaque volume in patients with acute coronary syndrome ( ACS ) . However , the benefits of early statin administration on long-term outcomes remain unclear . We therefore examined whether the early initiation of statin in patients with ACS improves long-term prognosis . METHODS AND RESULTS The Extended-ESTABLISH trial included 180 patients with ACS who underwent emergency percutaneous coronary intervention ( PCI ) . These patients were r and omized here to groups given either early intensive lipid-lowering therapy ( n=90 ; atorvastatin 20 mg/day ) or st and ard care ( control , n=90 ) within 48 h of events . Baseline characteristics between the two groups did not significantly differ at the time of ACS onset . Six months after PCI , all patients were treated with statins to achieve an LDL-C value of < 100 mg/dL. We compared the first occurrence of major adverse cardiac and cerebrovascular events ( MACCE ) . Prognostic data were fully documented during the entire follow-up period ( mean , 1538+/-707 days ) . Cumulative event-free survival was significantly higher in the atorvastatin , than in the control group ( p=0.041 ; log-rank test ) . Furthermore , by adjusting for vali date d prognosticators , early statin administration was identified as a good predictor of MACCE ( HR 0.46 , 95%CI 0.23 - 0.86 ; p=0.015 ) . CONCLUSIONS In-hospital initiation of statin therapy immediately after ACS conferred long-term benefits and 6 months of intensive lipid-lowering therapy improved long-term clinical outcomes after PCI in patients with ACS Background Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture , which can lead to the development of acute coronary syndrome ( ACS ) . Elevated levels of serum inflammatory markers such as C-reactive protein ( CRP ) represent independent risk factors for further cardiovascular events . Recent evidence indicates that in addition to lowering cholesterol levels , statins also decrease levels of inflammatory markers . Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were design ed for very early secondary prevention . To our knowledge , no controlled trials have evaluated the potential benefits of statin therapy , beginning immediately at the time of hospital admission . A previous pilot study performed by our group focused on early initiation of cerivastatin therapy . We demonstrated a highly significant reduction in levels of inflammatory markers ( CRP and interleukin-6 ) . Based on these preliminary findings , we are conducting a clinical trial to evaluate the efficacy of another statin , fluvastatin , as an early intervention in patients with ACS . Methods The FACS-trial ( Fluvastatin in the therapy of Acute Coronary Syndrome ) is a multicenter , r and omized , double-blind , placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission . The study will enroll 1,000 participants admitted to hospital for ACS ( both with and without ST elevation ) . The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers ( CRP and interleukin-6 ) and on pregnancy associated plasma protein A ( PAPP-A ) . A combined secondary endpoint is 30-day and one-year occurrence of death , nonfatal myocardial infa rct ion , recurrent symptomatic ischemia , urgent revascularization , and cardiac arrest . Conclusion The primary objective of the FACS trial is to demonstrate that statin therapy , when started immediately after hospital admission for ACS , results in reduction of inflammation and improvement of prognosis . This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins OBJECTIVES This study sought to determine if in addition to st and ard preventive measures on-admission , high-dose rosuvastatin exerts a protective effect against contrast-induced acute kidney injury ( CI-AKI ) . BACKGROUND Patients with acute coronary syndrome ( ACS ) are at high risk for CI-AKI , and the role of statin pre-treatment in preventing renal damage remains uncertain . METHODS Consecutive statin-naïve non-ST elevation ACS patients scheduled to undergo early invasive strategy were r and omly assigned to receive rosuvastatin ( 40 mg on admission , followed by 20 mg/day ; statin group n = 252 ) or no statin treatment ( control group n = 252 ) . CI-AKI was defined as an increase in creatinine concentration of ≥0.5 mg/dl or ≥25 % above baseline within 72 h after contrast administration . RESULTS The incidence of CI-AKI was significantly lower in the statin group than in controls ( 6.7 % vs. 15.1 % ; adjusted odds ratio : 0.38 ; 95 % confidence interval [ CI ] : 0.20 to 0.71 ; p = 0.003 ) . The benefits against CI-AKI were consistent , even applying different CI-AKI definition criteria and in all the pre-specified risk categories . The 30-day incidence of adverse cardiovascular and renal events ( death , dialysis , myocardial infa rct ion , stroke , or persistent renal damage ) was significantly lower in the statin group ( 3.6 % vs. 7.9 % , respectively ; p = 0.036 ) . Moreover , statin treatment given on admission was associated with a lower rate of death or nonfatal myocardial infa rct ion at 6 month follow-up ( 3.6 % vs. 7.2 % , respectively ; p = 0.07 ) . CONCLUSIONS High-dose rosuvastatin given on admission to statin-naïve patients with ACS who are scheduled for an early invasive procedure can prevent CI-AKI and improve short-term clinical outcome . ( Statin Contrast Induced Nephropathy Prevention [ PRATO-ACS ] ; NCT01185938 ) BACKGROUND : Patients with heterozygous familial hypercholesterolemia ( FH ) and coronary heart disease have high mortality rates . However , in an era of high-dose statin prescription after acute coronary syndrome ( ACS ) , the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated . We compared coronary event rates between patients with and without FH after ACS . METHODS : We studied 4534 patients with ACS enrolled in a multicenter , prospect i ve cohort study in Switzerl and between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions : the American Heart Association definition , the Simon Broome definition , and the Dutch Lipid Clinic definition . We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infa rct ion and adjusted for age , sex , body mass index , smoking , hypertension , diabetes mellitus , existing cardiovascular disease , high-dose statin at discharge , attendance at cardiac rehabilitation , and the GRACE ( Global Registry of Acute Coronary Events ) risk score for severity of ACS . RESULTS : At the 1-year follow-up , 153 patients ( 3.4 % ) had died , including 104 ( 2.3 % ) of fatal myocardial infa rct ion . A further 113 patients ( 2.5 % ) experienced nonfatal myocardial infa rct ion . The prevalence of FH was 2.5 % with the American Heart Association definition , 5.5 % with the Simon Broome definition , and 1.6 % with the Dutch Lipid Clinic definition . Compared with patients without FH , the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses , although patients with FH were > 10 years younger . However , after multivariable adjustment including age , the risk was greater in patients with FH than without , with an adjusted hazard ratio of 2.46 ( 95 % confidence interval , 1.07–5.65 ; P=0.034 ) for the American Heart Association definition , 2.73 ( 95 % confidence interval , 1.46–5.11 ; P=0.002 ) for the Simon Broome definition , and 3.53 ( 95 % confidence interval , 1.26–9.94 ; P=0.017 ) for the Dutch Lipid Clinic definition . Depending on which clinical definition of FH was used , between 94.5 % and 99.1 % of patients with FH were discharged on statins and between 74.0 % and 82.3 % on high-dose statins  . CONCLUSIONS : Patients with FH and ACS have a > 2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins Context While the benefits of statins in the primary and secondary prevention of coronary artery disease are clear , the value of statin therapy in acute coronary syndromes is uncertain . Contribution Analyzing data from a large , international observational study of acute coronary syndromes , these investigators identified associations between statin use before and during acute coronary events and favorable outcomes . Caution s While these data suggest a potential benefit of statins during acute coronary events , trials are necessary to determine the most appropriate use of statins in the treatment of acute coronary events . The Editors Data from r and omized clinical trials support the efficacy of lipid-lowering medications , particularly statins , in the primary and secondary prevention of coronary artery disease ( 1 - 3 ) . The benefits of statins , however , were not readily apparent until after several months of therapy , suggesting that the drugs ' lipid-lowering capabilities were largely responsible . In vitro work has suggested that statins may have an abundance of pleiotropic effects ( 4 ) . These include modulation of inflammation , inhibition of platelet function and thrombosis , and enhancement of endothelial cell function . The demonstrated ability of statins to immediately affect basic pathophysiologic mechanisms has result ed in increased interest in their potential role in the setting of acute coronary syndromes . The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) trial found that early treatment with high-dose atorvastatin modestly reduced event rates of recurrent ischemia in statin-naive patients presenting with an acute coronary syndrome ( 5 ) . These observations , while intriguing , did not conclusively establish the role of statins in patients with acute coronary syndromes . In the MIRACL trial , the failure of statins to significantly affect more concrete trial end points ( for example , death or recurrent myocardial infa rct ion [ MI ] ) was disappointing . Whether this reflected a true lack of physiologic impact of early statin treatment or merely indicated that the study was underpowered to detect differences in these end points remains unclear . In a sub study using data from the Platelet Receptor Inhibition for Ischemic Syndrome Management ( PRISM ) trial in patients with acute coronary syndromes , patients already taking statins  had better short-term outcomes ( decreased risk for death or nonfatal MI ) than those not previously receiving statin therapy , unless statin therapy was discontinued in the hospital ( 6 ) . Initiation of statin therapy after the onset of an acute coronary syndrome appeared to be less effective than treatment with statins before symptom onset . Using data from the Global Registry of Acute Coronary Events ( GRACE ) project , a large , multinational , observational study of patients with acute coronary syndromes , we examined the association between previous statin therapy  , presentation characteristics of acute coronary syndromes , and hospital outcomes . We also examined the effect of early in-hospital statin therapy ( or withdrawal of statins ) on important hospital outcomes , including death or the development of recurrent MI or stroke . Methods Full details of the GRACE rationale and methods have been published elsewhere and are outlined below ( 7 - 9 ) . Site Selection The GRACE project is design ed to reflect an unbiased population of patients with acute coronary syndromes , regardless of geographic region . Currently , 94 hospitals located in 14 countries ( Argentina , Australia , Austria , Belgium , Brazil , Canada , France , Germany , Italy , New Zeal and , Pol and , Spain , the United Kingdom , and the United States ) are participating in this observational study . Patients entered in the registry must be at least 18 years of age and alive at the time of hospital presentation ; be admitted with an acute coronary syndrome as a presumptive diagnosis ( that is , have symptoms consistent with acute ischemia ) ; and have at least 1 of the following : electrocardiographic changes consistent with an acute coronary syndrome , serial increases in serum biochemical markers of cardiac necrosis , or documentation of coronary artery disease ( 7 - 9 ) . The qualifying acute coronary syndrome must not be precipitated by a significant noncardiovascular comorbid condition ( for example , trauma or surgery ) . To ensure the enrollment of an unbiased sample , the first 10 to 20 consecutive patients ( depending on each site 's patient volume ) are recruited from each site on a monthly basis . Where required , study investigators received approval from their local hospital ethics or institutional review board . Data Collection At each site , a trained coordinator collected data using a st and ardized case-report form . Data on demographic characteristics , medical history , presenting symptoms , duration of prehospital delay , biochemical and electrocardiographic findings , treatment practice s , and hospital outcome were collected . St and ardized definitions of all patient-related variables and clinical diagnoses were used . All cases were assigned to 1 of the following categories : ST-segment elevation MI , nonST-segment elevation MI , unstable angina , and other cardiac or noncardiac diagnoses that have been previously described ( 7 - 9 ) . St and ardized definitions were also used for selected hospital complications and outcomes . Patient Sample For the current study , patients who were subsequently found to have noncardiac or other cardiac ( nonacute coronary syndrome ) primary diagnoses and those who transferred into or out of GRACE registry hospitals were excluded from further consideration . Treatments defined as previous use were those taken by the patient on a long-term basis at home and within 7 days of the presenting event , based on the review of information contained in medical records and abstract ed by trained study physicians and nurses . Treatments received in the hospital ( within the first 24 hours or thereafter ) were categorized as within hospital . Agents prescribed for use after discharge from participating hospitals were categorized as at discharge . Patient treatment categories were defined according to the following groupings : no previous treatment with statins and no treatment with statins during hospitalization , no previous therapy with statins but statin therapy  instituted during hospitalization , previous therapy with statins and statin therapy continued during hospitalization , and previous  therapy with statins but statin therapy not continued during the index hospitalization . Statistical Analysis We used the chi-square tests for discrete variables to analyze differences in demographic and clinical characteristics , treatment practice s , clinical presentation ( ST-segment elevation vs. nonST-segment elevation , large infa rct [ creatine phosphokinase level > 2 times the upper limit of normal ] vs. small infa rct ) , subsequent diagnosis ( ST-segment elevation MI , nonST-segment elevation MI , unstable angina ) , and hospital complications ( death , congestive heart failure or pulmonary edema , cardiogenic shock , stroke , ventricular tachycardia or ventricular fibrillation , and cardiac arrest ) in relation to statin use . The Wilcoxon rank-sum test was used to analyze differences between respective comparison groups for continuous variables . While controlling for potentially confounding variables , we performed multivariate regression analyses to examine the association between previous statin therapy and hospital presentation ( ST-segment elevation vs. no ST-segment elevation , creatine phosphokinase level 2 times normal vs. creatine phosphokinase level < 2 times the upper limit of normal ) , as well as any association between previous or in-hospital statin therapy and hospital outcomes ( death , recurrent MI or MI after 24 hours , and stroke ) or a composite end point of all 3 outcomes . C and i date variables for inclusion in the regression models evaluating previous statin use and hospital presentation included patient age , sex , smoking status , diabetes , history of vascular disease ( previous MI , stroke , positive angiogram , peripheral vascular disease , percutaneous coronary intervention , or coronary artery bypass graft surgery ) , hypertension , hyperlipidemia , and previous therapies ( aspirin , angiotensin-converting enzyme [ ACE ] inhibitors , -blockers , and other lipid-lowering agents ) . C and i date variables for regression models evaluating previous or in-hospital statin use and hospital outcomes included all of the previously listed characteristics plus characteristics present at the time of hospital admission ( heart rate , systolic blood pressure , Killip class , ST-segment elevation or left bundle-branch block pattern , and positive cardiac enzymes ) and receipt of in-hospital therapies ( aspirin and other antiplatelet agents , -blockers , unfractionated heparin , low-molecular-weight heparin , glycoprotein IIb/IIIa inhibitors , cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass graft surgery ) . C and i date variables possibly associated with the outcomes of interest ( P < 0.25 after univariate analysis ) were included in the multivariate models . Variables for which the P value exceeded 0.05 were eliminated in a stepwise fashion so that only those that had a statistically significant association with the outcome of interest were included in the final regression models . Because of their clinical relevance and potential importance , age , sex , and history of hyperlipidemia were retained in the final multivariable models for clinical outcomes regardless of statistical significance . Final models were evaluated for goodness of fit by the HosmerLemeshow test . Because between-hospital variation in use of statin treatment could be considerable and potentially affect our study results , we adjusted for hospital r and om effects on the observed outcomes . We used a generalized estimating equation modeling technique , assuming patients were repeated measures within each hospital . Variable Albuminuria has been shown to be associated with mortality and cardiovascular events , independent of traditional cardiovascular risk factors . This suggests that albuminuria may not just represent glomerular damage , but may be a marker of more diffuse endothelial dysfunction . We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in  statin treated subjects after acute coronary syndromes ( ACS ) . Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial , in which patients who had been hospitalized with ACS were r and omized to pravastatin 40 mg ( st and ard therapy ) or atorvastatin 80 mg daily ( intensive therapy ) . In univariate analyses , increasing urine albumin concentration was associated with increased risk of myocardial infa rct ion , stroke , heart failure , and composite of death , myocardial infa rct ion and stroke at 2 years . However , in a multivariable model containing traditional cardiovascular risk factors , albuminuria was not an independent predictor of the primary PROVE IT endpoint of death , myocardial infa rct ion , unstable angina , revascularization and stroke , and was only an independent predictor of all-cause mortality at urinary albumin concentration > 300 mcg/ml . There was no significant change in urinary albumin concentration from enrolment to end of study in either the st and ard or intensive statin therapy groups , and no significant difference between treatment groups . Our results suggest that after an acute coronary syndrome in statin treated patients , microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors Background Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome ( ACS ) . The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear . The aim of our study was , therefore , to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS . Methods The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were r and omized at admission to fluvastatin 80 mg ( N = 78 ) or placebo ( N = 78 ) . Study medication was administered immediately after r and omization and then once daily for 30 days ; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75 % in the fluvastatin group and 78 % in the placebo group were on statin therapy . Results We did not demonstrate any difference between groups in the level of C-reactive protein , interleukin 6 , and pregnancy-associated plasma protein A on Day 2 and Day 30 ( primary endpoint ) . Fluvastatin-therapy , however , significantly reduced one-year occurrence of major adverse cardiovascular events ( 11.5 % vs. 24.4 % , odds ratio ( OR ) 0.40 , 95 % CI 0.17 - 0.95 , P = 0.038 ) . This difference was caused mainly by reduction of recurrent symptomatic ischemia ( 7.7 % vs. 20.5 % , OR 0.32 , 95 % CI 0.12 - 0.88 , P = 0.037 ) . Conclusions This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability . Fluvastatin therapy was , however , safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.Trial registration BACKGROUND Statin pretreatment before percutaneous coronary intervention ( PCI ) is associated with a reduced incidence of short-term adverse events and periprocedural myocardial infa rct ion ( MI ) . However , the long-term effects of statin pretreatment have not been evaluated . METHODS Consecutive 445 patients with acute coronary syndrome ( ACS ) who underwent PCI were r and omly assigned to receive no statin treatment before PCI ( control group , n=220 ) or to receive 40 mg rosuvastatin loading before PCI ( rosuvastatin group , n=225 ) . The incidence of major adverse cardiac events ( MACE ) , including cardiac death , non-fatal MI , non-fatal stroke , and any ischemia-driven revascularization , was assessed after 12 months . RESULTS During 11±3 months of follow-up , MACE occurred in 20.5 % of patients in the control group and 9.8 % of patients in the rosuvastatin group ( p=0.002 ) . The Kaplan-Meier curves showed that the incidence of death and non-fatal MI was significantly greater in the control group than in the rosuvastatin group ( hazard ratio , 3.71 ; p=0.021 ) . High-sensitivity C-reactive protein levels were less elevated in the rosuvastatin group than in the control group at 24 h after PCI . Multivariate analysis revealed that rosuvastatin loading was an independent predictor of a reduction in the risk of MACE at 12 months ( odds ratio , 0.5 ; p=0.006 ) . CONCLUSIONS High dose rosuvastatin loading before PCI significantly improved 12-month clinical outcomes in patients with ACS who underwent an early invasive strategy BACKGROUND The A-to-Z Trial is an ongoing international , multicenter , r and omized study design ed to investigate 2 issues concerning contemporary care of patients with acute coronary syndromes ( ACS ) . The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affects outcomes and safety when used as a therapy adjunctive to baseline treatment with tirofiban and aspirin in patients with non-ST-elevation ( nSTE ) ACS . The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based " accepted care " regimen of a lower-dose statin started 3 to 6 months after an acute event . METHODS The study is conceptually and functionally divided into 2 sequential parts-the " A " Aggrastat and " Z " Zocar phases . The primary A-phase end point is a composite of all-cause mortality , myocardial infa rct ion ( MI ) , and documented refractory ischemia at 7 days .  Both nSTE-ACS patients from the A phase and patients with ST-elevation ACS who meet specific risk criteria are eligible to enter the subsequent " Z " ( Zocor ) chronic phase ( Z phase ) . The primary end point of the Z phase is a composite of cardiovascular death , MI , readmission for ACS , and stroke . The trial will continue until 970 primary events have occurred in the Z-phase population . CONCLUSION This trial is evaluating 2 temporally connected sequences of phamacotherapy for ACS . At completion , trial results will provide definitive evidence regarding efficacy and safety of early , intensive statin therapy and better define the role of low-molecular-weight heparin in patients with nSTE ACS BACKGROUND Studies in Western population s have shown the benefits of pretreatment with atorvastatin in preventing cardiovascular events in patients , including those with acute coronary syndromes ( ACS ) , undergoing percutaneous coronary intervention ( PCI ) . However , data concerning the value of such therapy in Asian patients are limited . The primary objective of the present study is to evaluate the efficacy of atorvastatin in reducing cardiovascular outcomes in Asian patients with non-ST-segment elevation (NSTE)-ACS following hospital admission for early PCI ( within 72 h of the onset of symptoms ) . Secondary objectives are to assess the effects of atorvastatin on cardiac biomarker levels , and the safety and tolerability profile of atorvastatin . METHODS This study is a prospect i ve , multicenter , open-label trial design ed to enroll 350 statin-naïve patients with NSTE-ACS scheduled for PCI in China and the Republic of Korea . Patients are r and omized to either usual care or atorvastatin treatment groups , with patients in both treatment groups receiving usual care including atorvastatin 40 mg/day for 30 days post-PCI . Patients in the atorvastatin group receive additional doses of atorvastatin 80 mg at 12 h pre-PCI and 40 mg at 2 h pre-PCI . The primary end point is the incidence of major adverse cardiac events ( death , myocardial infa rct ion , and target vessel revascularization ) at 30 days post-PCI . CONCLUSIONS The present study will provide valuable insights into whether the benefits of atorvastatin pretreatment extend to Asian patients with ACS undergoing interventions . Enhanced treatment of these patients will be an important contribution towards alleviating the increasing burden of cardiovascular disease in Asian countries BACKGROUND Following acute coronary syndrome ( ACS ) , the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol ( LDL-C ) even within the setting of intensive statin treatment . Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab , a fully human monoclonal antibody to PCSK9 , improves cardiovascular outcomes after ACS . DESIGN This Phase 3 study will r and omize approximately 18,000 patients to receive biweekly injections of alirocumab ( 75 - 150 mg ) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infa rct ion or unstable angina . Qualifying patients are treated with atorvastatin 40 or 80 mg daily , rosuvastatin 20 or 40 mg daily , or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria : LDL-C ≥ 70 mg/dL , non-high-density lipoprotein cholesterol ≥ 100 mg/dL , or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death , acute myocardial infa rct ion , hospitalization for unstable angina , or ischemic stroke . The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years , providing 90 % power to detect a 15 % hazard reduction . Adverse events of special interest include allergic events and injection site reactions . Interim analyses are planned when approximately 50 % and 75 % of the targeted number of primary end points have occurred . SUMMARY ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS The incidence of adverse outcomes after percutaneous coronary intervention ( PCI ) is higher in women than in men . Statins reduce the likelihood of cardiovascular events arising in patients with coronary artery disease ( CAD ) , but the impact of gender difference on long-term outcomes of PCI for CAD under statin treatment has not been established . We prospect ively enrolled 3,580 consecutive patients with CAD who were treated by PCI at our institution between 2000 and 2011 . Among these , 2,009 ( 43.9 % ; male , n = 1619 ; female , n = 390 ) were under statin therapy at the time of PCI . We evaluated the incidence of major adverse cardiac events ( MACE ) including all-cause death and acute coronary syndrome ( ACS ) . Age was significantly more advanced and the prevalences of hypertension and chronic kidney disease were higher among the female , than the male patients . Low-density lipoprotein cholesterol levels were significantly higher in women than in men ( 111.5 ± 38.9 vs. 107.5 ± 3 3.9 mg/dL , p = 0.04 ) . During a median follow-up period of 6.3 years , MACE that occurred in 336 ( 16.7 % ) patients included 206 ( 10.2 % ) with all-cause death and 154 ( 7.7 % ) with ACS . The cumulative rate of MACE tended to be higher in women than in men but the difference did not reach significance ( 19.7 vs. 16.0 % ; p = 0.08 , log-rank test ) . Multivariable Cox regression analysis showed that being female was not associated with MACE after adjusting for age ( HR 1.22 ; 95 % CI 0.94–1.57 ; p = 0.13 ) and other variables ( HR 1.14 ; 95 % CI 0.86–1.49 ; p = 0.35 ) . Long-term clinical outcomes were comparable between male and female patients with coronary artery disease who were administered with statins and underwent PCI even though the baseline characteristics were worse among the females OBJECTIVES This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND R and omized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infa rct ion in patients with stable angina during elective PCI ; however , this therapy has not been tested in patients with ACS . METHODS A total of 171 patients with non-ST-segment elevation ACS were r and omized to pretreatment with atorvastatin  ( 80 mg 12 h before PCI , with a further 40-mg preprocedure dose [ n = 86 ] ) or placebo ( n = 85 ) . All patients were given a clopidogrel 600-mg loading dose . All patients received long-term atorvastatin treatment thereafter ( 40 mg/day ) . The main end point of the trial was a 30-day incidence of major adverse cardiac events ( death , myocardial infa rct ion , or unplanned revascularization ) . RESULTS The primary end point occurred in 5 % of patients in the atorvastatin arm and in 17 % of those in the placebo arm ( p = 0.01 ) ; this difference was mostly driven by reduction of myocardial infa rct ion incidence ( 5 % vs. 15 % ; p = 0.04 ) . Postprocedural elevation of creatine kinase-MB and troponin-I was also significantly lower in the atorvastatin group ( 7 % vs. 27 % , p = 0.001 and 41 % vs. 58 % , p = 0.039 , respectively ) . At multivariable analysis , pretreatment with atorvastatin conferred an 88 % risk reduction of 30-day major adverse cardiac events ( odds ratio 0.12 , 95 % confidence interval 0.05 to 0.50 ; p = 0.004 ) . CONCLUSIONS The ARMYDA-ACS trial indicates that even short-term pretreatment with atorvastatin may improve outcomes in patients with ACS undergoing early invasive strategy . These findings may support routine use of high-dose statins before intervention in patients with ACS BACKGROUND There is a strong correlation between adverse clinical events and peak values of myocardial necrosis markers in non-ST-elevation acute coronary syndrome patients . In this clinical setting , high-dose statin treatment exerts acute beneficial effects against renal and myocardial damage . The aim of this report was to evaluate if , on admission , high-dose rosuvastatin can exert cardioprotective effects when administered in addition to high-dose clopidogrel . METHODS In the PRATO-ACS trial , 504 consecutive statin-naïve non-ST-elevation acute coronary syndrome patients scheduled for early invasive strategy and pretreated with high-dose clopidogrel  were r and omly assigned to rosuvastatin ( 40 mg on admission followed by 20 mg/d ; statin group , n = 252 ) or no statin treatment ( control group , n = 252 ) . Serial myocardial biomarker sample s were collected before and after angiography and /or percutaneous coronary intervention . The primary end point was the peak level of cardiac troponin I ( cTnI ) during the index event . RESULTS Statin-treated patients presented median cTnI peak values similar to controls ( 3.9 [ 0.6 - 12.8 ] vs 3.5 [ 1.2 - 11.9 ] ng/mL , respectively ; P = .60 ] ; no differences were found between the 2 groups in cTnI and creatine kinase-MB values at any time point , in either preangiography and postangiography peak values or their cumulative release . In patients su bmi tted to percutaneous coronary intervention , periprocedural myocardial infa rct ion occurred in 8 ( 4.7 % ) of 171 statin-treated and 7 ( 4.3 % ) of 162 control patients ( P = .87 ) . CONCLUSION In the PRATO-ACS trial , early high-dose rosuvastatin did not show cardioprotective effects when administered in addition to high-dose clopidogrel Background Hypercholesterolemia has been identified as a major risk factor for the development of coronary artery disease . The aim of this study was to assess the effect of a Mediterranean diet on the development of non-fatal acute coronary syndromes ( ACS ) in hypercholesterolemic people , with or without statin treatment . Methods During 2000–2001 , 848 r and omly selected patients with a first event of coronary heart disease and 1078 cardiovascular disease-free people , matched to the patients by sex , age and region , were studied . Treatment of hypercholesterolemia with statin and the adoption of a Mediterranean diet were recorded . Results Hypercholesterolemia was present in 534 ( 63 % ) out of 848 coronary patients and 399 ( 37 % ) out of 1078 control participants . One hundred and seventy-one ( 32 % ) of the hypercholesterolemic patients and 168 ( 42 % ) of the hypercholesterolemic control participants were treated with statins and also followed a Mediterranean diet . The analysis showed that the combination of a Mediterranean diet and  statin medical therapy is associated with an additional reduction of the coronary risk ( odds ratio = 0.57 , P < 0.01 ) , independently from cholesterol levels and the other cardiovascular factors . Conclusion The adoption of a Mediterranean diet by hypercholesterolemic people seems to reinforce the benefits from statin treatment on lipid levels and reduces the risk of developing ACS . However , it is hard to cl aim that our findings suggest causal evidence , and in order to explain the potential common mechanism between diet and statin treatment much remains to be learned BACKGROUND Inflammation promotes acute coronary syndromes ( ACS ) and ensuing clinical complications . It is well known that statins decrease the risk of coronary events and may benefit the stabilization of atherosclerotic plaque with their anti-inflammatory effects . We investigated the effects of different doses of fluvastatin on serum concentrations of high-sensitive C-reaction protein ( hs-CRP ) and tumor necrosis factor-alpha ( TNF-alpha ) in the early phase of ACS . METHODS We prospect ively r and omized 60 patients with ACS to 3 groups : ( 1 ) group A ( n=20 ) : were given routine therapy ; ( 2 ) group B ( n=20 ) : were administrated routine therapy with 40 mg/d oral fluvastatin ;  ( 3 ) group C ( n=20 ) : received routine therapy with 80 mg/d oral fluvastatin .  Twenty patients with stable coronary heart disease served as controls . The following-up period was 7 days . By immunoturbidimetric assay and ELISA methods the serum concentrations of hs-CRP and TNF-alpha were measured before and after therapy . RESULTS ( 1 ) The serum concentrations of hs-CRP and TNF-alpha in patients with ACS was significantly higher than those in the control group ( P<0.05 ) . ( 2 ) After 1 week of therapy , the serum concentrations of hs-CRP and TNF-alpha were significantly lower in group B and group C ( all P<0.01 ) , especially in group C. ( 3 ) The serum concentrations of hs-CRP and TNF-alpha did not correlate to the concentrations of TC , TG , LDL-C , or HDL-C. CONCLUSION Early fluvastatin intervention decreases dose-dependently the serum concentrations of hs-CRP and TNF-alpha of patients with ACS . The high-dose fluvastatin invention may play a stronger anti-inflammatory effect in ACS patients . The anti-inflammatory effect of fluvastatin may be beyond the lipid lowering BACKGROUND High-dose statins are used in acute coronary syndromes ( ACS ) to reduce inflammation . The aim of the study was the evaluation of the influence of low-dose atorvastatin ( 20 mg ) on selected inflammatory parameters and clinical outcomes after ACS . METHODS Seventy eight patients ( pts ) with ACS were r and omly divided into group A ( 39 pts ) taking atorvastatin , and group NA ( 39 pts ) not taking any statin for the following six weeks . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , monocyte chemoattractant protein-1 ( MCP-1 ) and tumour necrosis factor alpha ( TNFa ) levels were measured on the first and the fifth days and six weeks after ACS . RESULTS There was no significant CRP and IL-6 level decrease in group A ( CRP--62 % ; IL-6 - 73 % ) or group NA ( CRP-44 % ; IL-6 - 62 % ) . There was also no significant change in TNFa levels . The MCP-1 level finally reached the level of significant difference ( p < 0.04 ) . Cardiovascular events ( MACE ) and the restenosis rates did not differ between the groups . CONCLUSIONS Low-dose atorvastatin does not have a significant influence on cooling down inflammation in ACS , and MCP-1 can be used as an early indicator of statin anti-inflammatory activity . Furthermore , it does not reduce MACE or restenosis rates despite its influence on MCP-1 levels OBJECTIVE To investigate the changes of electrocardiogram ( ECG ) and impact of early invasive strategy in patients with acute coronary syndrome ( ACS ) without ST-segment elevation . METHODS Five hundred and forty-five consecutive ACS patients without ST-segment elevation were r and omly assigned to early conservative treatment group and early invasive treatment group . The combined cardiovascular events , including cardiac death , nonfatal myocardial infa rct ion , nonfatal heart failure , and re-hospitalization due to recurrent ischemia angina , within 30 days and 6 months were analyzed and the effects of varied ECG changes and different intervention strategies on outcomes of patients were evaluated . RESULTS The incidences of each and combined cardiovascular events were higher in the patients with ST-segment depression than in those without ST-segment depression . ST-segment depression was one of independent predictive factors for an increase in cardiovascular events within 6 months ( OR 3.864 , 95 % CI : 1.668 approximately 9.451 , P < 0.001 ) . Early invasive strategy was associated with a lower rate of re-hospitalization due to recurrent ischemia angina within 30 days and a decreased incidence of combined cardiovascular events within 30 days and 6 months in comparison with the early conservative treatment group ( all P < 0.05 ) . Subgroup analysis implied that incidences of combined cardiovascular events within 30 days and 6 months decreased significantly only in patients with ST-segment depression treated with early invasive strategy , and no such benefit was seen in the patients without ST-segment depression . CONCLUSION ST-segment depression is an effective indicator for identifying those patients with non-ST segment elevation ACS most likely to benefit from early invasive strategy . Early invasive strategy markedly decreases the cardiovascular events in ACS patients with ST-segment depression than early conservative strategy BACKGROUND The recent North American and European practice guidelines in patients with non-ST-segment elevation acute coronary syndrome ( nSTE ACS ) recommend glycoprotein IIb/IIIa ( GpIIb-IIIa ) inhibition in patients undergoing an early invasive treatment strategy . However , the guidelines are not explicit regarding the timing of initiation of GpIIb-IIIa antagonists , and there is marked variation in clinical practice regarding their use . STUDY DESIGN The EARLY ACS trial will enroll 10,500 patients in a prospect i ve , r and omized , double blind , international , multicenter investigation of early eptifibatide compared with placebo ( with provisional eptifibatide in the catheterization laboratory ) in patients with high-risk nSTE ACS in whom an invasive strategy is planned no sooner than the next calendar day . The primary efficacy end point is the 96-hour composite of all-cause mortality , nonfatal myocardial infa rct ion , recurrent ischemia requiring urgent revascularization , or need for thrombotic bailout with GpIIb-IIIa inhibitor during percutaneous coronary intervention . The key secondary end point is the composite of death or nonfatal myocardial infa rct ion within 30 days of enrollment . IMPLICATION S The EARLY ACS trial will be the largest study to date to evaluate the utility of early GpIIb-IIIa inhibition in patients with nSTE ACS in whom an invasive approach is planned . This trial will provide important evidence regarding the benefit of initiating eptifibatide early after presentation with high-risk ACS versus delayed provisional use after coronary angiography . Furthermore , it will explore the ability of biomarkers to identify high-risk patients who may benefit from such an early aggressive approach OBJECTIVE To investigate the relationship between thrombolysis in myocardial infa rct ion ( TIMI ) risk score and efficacy of different treatment strategies in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . METHODS From Oct. 2001 to Oct. 2003 , 545 consecutive patients with NSTE-ACS were r and omly assigned to early conservative strategy ( n = 284 ) or early invasive strategy group ( n = 261 ) . The combined cardiovascular events ( a combination of cardiac death , nonfatal myocardial infa rct ion , nonfatal heart failure and re-hospital admission due to recurrent ischemia angina ) within 30 days and 6 months were analyzed and related to the TIMI risk score at admission . RESULTS Rehospitalization due to recurrent ischemia angina of 30 days and the combined cardiovascular events of 30 days and 6 months were significantly lower in early invasive strategy group ( 3.5 % , 10.0 % , 21.1 % ) compared with early conservative strategy group ( 8.1 % , 16.9 % , 28.2 % , all P < 0.05 ) . Subgroup analysis indicated early invasive strategy could significantly decrease the 30 d incidence of the combined end point events in patients with high TIMI risk score and the 6 months incidence of the combined end point events in patients with moderate and high TIMI risk score ( all P < 0.01 ) , but the incidence was similar between the two different strategies in patients with low TIMI risk score . CONCLUSIONS Early invasive strategy may significantly reduce combined cardiovascular events in NSTE-ACS patients with moderate and high TIMI risk score compared with early conservative strategy OBJECTIVE To investigate the effect of early invasive strategy on early and late outcomes in high-risk patients with non-ST-segment elevation acute coronary syndromes ( ACS ) . METHODS Five hundred and forty-five patients of ACS without ST-segment elevation were r and omly assigned to an  early conservative strategy  ( 284 cases ) or early invasive strategy group  ( 261 cases ) , who were enrolled consecutively from Oct. , 2001 to Oct. , 2003 . The combined cardiovascular events ( a combination of cardiac death , nonfatal myocardial infa rct ion , nonfatal heart failure and hospital readmission due to recurrent ischemic angina ) within 30 days and 6 months were analyzed and the effects of early invasive strategy on early and late outcomes in high-risk patients with increased TnI or hs-CRP levels were evaluated . RESULTS As compared with early conservative strategy , early invasive strategy lowered the rate of hospital readmission due to recurrent ischemic angina of 30 d and the combined cardiovascular events of 30 d and 6 months ( all P < 0.05 ) . Subgroup analysis indicated early invasive strategy could significantly decrease the incidences of the combined cardiovascular events of 30 d and 6 months and the hard end point events of 6 months in patients with increased TnI or hs-CRP levels ( all P < 0.01 ) , but no such changes could be seen in patients with normal TnI or hs-CRP levels , as compared with early conservative strategy . CONCLUSIONS Early invasive strategy decreases significantly cardiovascular events and improves the early and late outcomes in high-risk patients with increased TnI or hs-CRP levels Background —Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome ( ACS ) . We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol ( LCL-C ) lowering . The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS . Methods and Results —Seventy patients with ACS were enrolled . All patients underwent emergency coronary angiography and percutaneous coronary intervention ( PCI ) .  They were r and omized to intensive lipid-lowering therapy ( n=35 ; atorvastatin 20 mg/d ) or control ( n=35 ) groups after PCI . Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients ( atorvastatin , n=24 ; control , n=24 ) . LDL-C level was significantly decreased by 41.7 % in the atorvastatin group compared with the control group , in which LDL-C was increased by 0.7 % ( P<0.0001 ) . Plaque volume was significantly reduced in the atorvastatin group ( 13.1±12.8 % decrease ) compared with the control group ( 8.7±14.9 % increase ; P<0.0001 ) . Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level ( R=0.456 , P=0.0011 ) and percent LDL-C reduction ( R=0.612 , P<0.0001 ) , even in patients with baseline LDL-C < 125 mg/dL. Conclusions —Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS . Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction , even in patients with low baseline Background — Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is associated with the risk of cardiovascular ( CV ) events in population -based studies . The prognostic value of Lp-PLA2 in patients with acute coronary syndromes ( ACS ) has not been established . Methods and Results — Plasma levels of Lp-PLA2 activity were measured at baseline ( n=3648 ) and 30 days ( n=3265 ) in patients r and omized to atorvastatin 80 mg/d or pravastatin 40 mg/d after ACS in the PROVE IT-TIMI 22 ( PRavastatin Or atorVastatin  Evaluation and Infection Therapy – Thrombolysis In Myocardial Infa rct ion ) trial . The primary end point was death , myocardial infa rct ion , unstable angina , revascularization , or stroke ( mean follow-up 24 months ) . At baseline after ACS , the risk of recurrent CV events was similar across all quintiles of Lp-PLA2 activity ( Ptrend=0.88 ) . Overall , mean levels of Lp-PLA2 were lower at 30 days of follow-up than at baseline ( 35.7 versus 40.9 nmol · min−1 · mL−1 , P<0.001 ) . In particular , treatment with atorvastatin 80 mg/d was associated with a 20 % reduction in Lp-PLA2 activity ( P<0.001 ) , whereas Lp-PLA2 rose 3.6 % with pravastatin 40 mg/d ( P<0.001 ) . Patients with 30-day Lp-PLA2 activity in the highest quintile were at significantly increased risk of recurrent CV events compared with those in the lowest quintile ( 26.4 % versus 17.6 % , Ptrend=0.002 ) . After adjustment for cardiac risk factors , treatments , achieved low-density lipoprotein ( LDL ) , and C-reactive protein , Lp-PLA2 activity in the highest quintile remained independently associated with a higher risk of recurrent CV events ( adjusted hazard ratio 1.33 , 95 % confidence interval [ CI ] 1.01 to 1.74 ) . Conclusions — Lp-PLA2 is not useful for risk stratification when measured early after ACS . At 30 days , Lp-PLA2 activity is significantly lowered with high-dose statin therapy and is associated with an increased risk of CV events independent of C-reactive protein and LDL cholesterol levels BACKGROUND The mechanism underlying rapid , statin-induced event reduction in patients with an acute coronary syndrome ( ACS ) remains to be clarified . AIM The primary objective is to compare the efficacy of rosuvastatin 20 mg/day and atorvastatin 80 mg/day in reducing the apolipoprotein B/apolipoprotein A-1 ( apoB/apoA-1 ) ratio at three months , in ACS patients . Secondary objectives include a comparison of the effects of early-started rosuvastatin and placebo on inflammatory markers . METHODS This is a r and omized , double-blind , parallel-group study . Patients with non-ST-segment elevation ACS , symptom onset less than 48 h before admission , and for whom a percutaneous coronary intervention is planned , are eligible for inclusion and are r and omized into three groups ( G1 , G2 and G3 ) . The study comprises two double-blind periods . Period 1 starts at hospital admission and lasts until Day 0 ( discharge or less or equal to 6 days after admission ) ; patients in G1 receive one tablet of rosuvastatin 20 mg/day and patients in G2 and G3 receive one matching placebo tablet per day . Period 2 starts at Day 0 and lasts for three months ; patients in G1 continue to receive rosuvastatin 20 mg/day , patients in G2 receive rosuvastatin 20 mg/day and patients in G3 receive atorvastatin 80 mg/day . Recruitment of 1075 patients will ensure an 80 power to detect a 3 % difference in percentage change in the apoB/apoA-1 ratio and a 20 % difference in percentage change in high-sensitivity C-reactive protein . RESULTS Inclusion phase is complete ; results will be reported at a later date . CONCLUSION This is the first trial investigating the effect of statins on apolipoproteins in ACS patients AIM To define the long-term outcome of patients presenting with acute coronary syndrome [ ST-segment elevation myocardial infa rct ion ( STEMI ) , and non-STEMI and unstable angina acute coronary syndrome ( ACS ) without biomarker elevation ] and to test the hypothesis that the GRACE ( Global Registry of Acute Coronary Events ) risk score predicts mortality and death/MI at 5 years . METHODS AND RESULTS In the GRACE long-term study , UK and Belgian centres prospect ively recruited and followed ACS patients for a median of 5 years ( 1797 days ) . Primary outcome events : deaths , cardiovascular deaths ( CVDs ) and MIs . Secondary events : stroke and re-hospitalization for ACS . There were 736 deaths , 19.8 % ( 482 CVDs , 13 % ) and 347 ( 9.3 % ) MIs ( > 24 h ) , 261 strokes ( 7.7 % ) , and 452 ( 17 % ) subsequent revascularizations . Rehospitalization was common : average 1.6 per patient ; 31.2 % had > 1 admission , 9.2 % had 5 + admissions . These events were despite high rates of guideline indicated therapies . The GRACE score was highly predictive of all-cause death , CVD , and CVD/MI at 5 years ( death : χ(2 ) likelihood ratio 632 ; Wald 709.9 , P < 0.0001 , C-statistic 0.77 ; for CVD C-statistic 0.75 , P < 0.0001 ; CVD/MI C-statistic 0.70 , P < 0.0001 ) . Compared with the low-risk GRACE stratum ( ESC Guideline criteria ) , those with intermediate [ hazard ratio ( HR ) 2.14 , 95 % CI 1.63 , 2.81 ] and those with high-risk ( HR 6.36 , 95 % CI 4.95 , 8.16 ) had two- and six-fold higher risk of later death ( Cox proportional hazard ) . A l and mark analysis after 6 months confirmed that the GRACE score predicted long-term death ( χ(2 ) likelihood ratio 265.4 ; Wald 289.5 , P < 0.0001 ) . Although in-hospital rates of death and MI are higher following STEMI , the cumulative rates of death ( and CVD ) were not different , by class of ACS , over the duration of follow-up ( Wilcoxon = 1.5597 , df = 1 , P = 0.21 ) . At 5 years after STEMI 269/1403 ( 19 % ) died ; after non-STEMI 262/1170 ( 22 % ) after unstable angina ( UA ) 149/850 ( 17 % ) . Two-thirds ( 68 % ) of STEMI deaths occurred after initial hospital discharge , but this was 86 % for non-STEMI and 97 % for UA . CONCLUSION The GRACE risk score predicts early and 5 year death and CVD/MI . Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI . Their morbidity burden is high ( MI , stroke , readmissions ) and the substantial late mortality in non-STE ACS is under-recognized . The findings highlight the importance of pursuing novel approaches to diminish long-term risk Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy . We hypothesized that early use of statins would decrease cardiovascular events , including heart failure in patients with acute myocardial infa rct ion ( AMI ) . To examine the effect of statins in Japanese patients with AMI , a prospect i ve , r and omized , open-label trial was conducted in 486 patients with normal total cholesterol levels . Patients were r and omly assigned to receive any available statin ( n = 241 ) within 96 hours of AMI onset or no statin ( n = 245 ) and were followed for up to 24 months . The primary end point was a composite of cardiovascular death , nonfatal AMI , recurrent symptomatic myocardial ischemia , congestive heart failure , and stroke . Event rate for the primary end point was lower in the statin group than in the nonstatin group ( 6.1 % vs 11.4 % , p = 0.0433 ) . The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia ( p = 0.0154 and 0.0264 , respectively ) . In conclusion , early lipid-lowering therapy with statins  decreases recurrent cardiovascular events , in particular , congestive heart failure BACKGROUND The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ( JAPAN-ACS ) trial has found that early aggressive statin therapy in patients with acute coronary syndrome ( ACS ) significantly reduces the plaque volume ( PV ) of non-culprit coronary lesions . The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy . METHODS AND RESULTS Serial intravascular ultrasound observations over 8 - 12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin .  Linear regression analysis identified the presence of diabetes mellitus ( DM ) and PV at baseline as inhibiting factors , and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression . Significant correlation between % change of PV and low-density lipoprotein cholesterol ( LDL-C ) level was found in patients with DM ( n=73 , P<0.05 , r=0.4 ) , whereas there was no significant correlation between the 2 parameters in patients without DM ( n=178 ) . CONCLUSIONS The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts . Moreover , vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM OBJECTIVES We sought to determine whether aspirin withdrawal is an encountered situation in coronary disease patients who relapsed . BACKGROUND Despite the recognized benefits of aspirin in coronary disease , and because of the threat of bleeding or poor compliance , aspirin intake is sometimes stopped . It is not known whether withdrawal of aspirin can be harmful in coronary-disease patients . METHODS Between September 1999 and April 2002 , a total of 1,236 patients hospitalized for acute coronary syndrome ( ACS ) were question ed in order to determine whether aspirin intake had been interrupted . RESULTS Fifty-one of these ACSs occurred within 1 month after aspirin withdrawal . This represents 4.1 % of all coronary events but 13.3 % of recurrences . Among those patients who relapsed , the incidence of ST-segment elevation ACS was higher in those who stopped aspirin when compared to the 332 patients who did not stop aspirin ( 39 % vs. 18 % ; p = 0.001 ) . Ten ( 20 % ) cases involved a thrombosis of an uncoated stent implanted on average 15.5 + /- 6.5 months previously . Mean delay between aspirin withdrawal and the acute coronary event was 10 + /- 1.9 days . Reasons for aspirin withdrawal included minor surgery in 7 cases , fibroscopy in 8 cases , dental treatment in 13 cases , bleeding in 3 cases , and patient non-compliance in 20 cases . CONCLUSIONS Our results support the hypothesis that  aspirin withdrawal in coronary patients may represent a real risk for the occurrence of a new coronary event . Many cases involved late uncoated-stent thrombosis . Assessment of the exact incidence of coronary recurrences after aspirin withdrawal will need prospect i ve studies BACKGROUND New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T ( cTnT ) and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) in patients with non-ST-elevation acute coronary syndrome ( nSTE-ACS ) provides unique prognostic information . The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy . METHODS Baseline sample s for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT r and omized to an early or a selective invasive strategy . Patients were followed-up for the occurrence of death , myocardial infa rct ion ( MI ) , and rehospitalization for angina . RESULTS We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease . Mortality by 1 year was 7.3 % in the highest quartile ( > or = 1170 ng/L for men , > or = 2150 ng/L for women ) compared with 1.1 % of patients in the lower 3 quartiles ( P < .0001 ) . N-terminal pro-brain natriuretic peptide ( highest quartile vs lower 3 quartiles ) was a strong independent predictor of mortality ( hazard ratio 5.0 , 95 % CI 2.1 - 11.6 , P = .0002 ) . However , NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year . Furthermore , we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level . CONCLUSIONS We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy OBJECTIVE To investigate the predictive value of positive troponin I ( TnI ) on early prognosis in patients with non-ST-segment elevation acute coronary syndrome ( NSTE ACS ) , and to evaluate TnI as a predictor of risk for the combined end points of cardiac events in NSTE ACS . METHODS 545 patients with non-ST-elevation acute coronary syndrome were double-blind r and omly enrolled in two groups of study ,  receiving invasive or noninvasive treatment  , respectively . At admission , all patients ' baseline levels of TnI and CK-MB were determined and related to outcome at 30th day and 6th month of follow-up . Aspirin , beta-blocker , ACEI and LWMH were given depending on patients ' clinical condition . RESULTS After a follow up of 6 months , hospitalization because of recurrent angina pectoris and combined end points of cardiac events in TnI positive patients occurred much more as compared with that in the TnI negative patients and the prognosis improved with early invasive interventional treatment strategy in the TnI positive patients ( P < 0.01 ) at 30th day and 6th month . For TnI negative patients , there was no difference between the two groups whether invasive or non-invasive therapy was given . CONCLUSIONS There is high recurrence rate of angina pectoris and increased number of combined end points of cardiac events in positive TnI patients during follow-up period . TnI served as an important risk factor in NSTE ACS patients and active early invasive intervention therapy should be the first choice for TnI positive patients , but it makes no more benefits for TnI negative patients BACKGROUND From a mechanistic st and point , obstructive sleep apnea ( OSA ) may further disturb cardiovascular homeostasis in the setting of acute coronary syndrome ( ACS ) . OBJECTIVE We sought to investigate if a st and ardized clinical diagnosis of OSA , in acute coronary syndrome patients , predicts the risk of cardiovascular events during hospitalization . METHODS In a prospect i ve cohort study , a group of 200 patients diagnosed with ACS between September 2005 and November 2007 were stratified by the Berlin Question naire ( BQ ) regarding the risk for OSA ( high or low risk ) . We tested if the subgroup of high risk for OSA was prone to a higher frequency of cardiovascular events . The primary endpoint evaluated was a composite outcome of cardiovascular death , recurrent cardiac ischemic events , acute pulmonary edema and stroke during hospitalization . RESULTS Ninety four ( 47 % ) patients assessed by the BQ were likely to have OSA . High risk for OSA was associated with a non-significant higher mortality ( 4.25 % vs 0.94 % ; p=0.189 ) , but a significant higher incidence of composite cardiovascular events ( 18.08 % vs 6.6 % ; p=0.016 ) . In the logistic regression model , multivariate predictors of composite cardiovascular events were age ( OR= 1.048 ; 95 % CI 1.008 to 1.090 ; p=0.019 ) , left ventricular ejection fraction ( OR= 0.954 ; 95 % CI 0.920 to 0.989 ; p=0.010 ) , and higher risk for OSA ( OR= 3.657 ; 95 % CI 1.216 to 10.996 ; p=0.021 ) . CONCLUSION The use of a simple and vali date d question naire ( BQ ) to identify patients with higher risk for OSA may help in the prediction of cardiovascular outcome during hospitalization . Moreover , our data suggests that OSA is very common in patients with ACS BACKGROUND Heart failure ( HF ) is an important cause of morbidity in patients with acute coronary syndromes ( ACS ) .  C-reactive protein ( CRP ) has been implicated in experimental models as exacerbating myocardial injury , but data regarding the clinical relationship of high-sensitivity CRP ( hsCRP ) and B-type natriuretic peptide ( BNP ) concentrations with the risk of HF after ACS are few . METHODS PROVE IT-TIMI 22 r and omized 4162 patients who had been stabilized after ACS to either intensive or moderate statin therapy .  hsCRP and BNP  were measured 30 days after r and omization . Hospitalizations for HF and cardiovascular death occurring after day 30 were assessed for a mean follow-up of 24 months . RESULTS Patients who developed HF had higher concentrations of hsCRP ( 3.7 mg/L vs 1.9 mg/L , P < 0.001 ) and BNP ( 59 ng/L vs 22 ng/L , P < 0.0001 ) . HF increased in a stepwise manner with hsCRP quartile [ adjusted hazard ratio ( HR(adj ) ) for Q4 vs Q1 , 2.5 ; P = 0.01 ] and BNP quartile ( HR(adj ) for Q4 vs Q1 , 5.8 ; P < 0.001 ) , with similar results obtained for HF and cardiovascular death . In a multivariable analysis , higher concentrations of hsCRP and BNP were both independently associated with HF [ HR(adj ) , 1.9 for hsCRP > 2.0 mg/L ( P = 0.01 ) and 4.2 for BNP > 80 ng/L ( P < 0.001 ) ] . Patients with increases in both markers were at the greatest risk of HF , compared with patients without an increased marker concentration ( HR(adj ) , 8.3 ; P = 0.01 ) . The benefit of intensive statin therapy in reducing HF was consistent among all patients , regardless of hsCRP or BNP concentration . CONCLUSIONS Both hsCRP and BNP measured 30 days after ACS are independently associated with the risk of HF and cardiovascular death , with the greatest risk occurring when both markers are increased AIMS HMG-CoA reductase inhibitors ( statins ) reduce cardiovascular mortality and morbidity in patients with stable coronary artery disease as well as acute coronary syndrome ( ACS ) . It is unclear how rapidly the beneficial effects of statins occur in patients with ACS and whether these drug properties are related to lipid lowering . METHODS AND RESULTS Patients with troponin-positive ACS ( n=35 ) were r and omized to 20 mg/day rosuvastatin therapy or to placebo treatment . Anti-inflammatory effects of rosuvastatin measured by lymphocyte intracellular cytokine production were taken before initiation of treatment and on days 1 , 3 , and 42 . Compared with placebo , rosuvastatin treatment significantly reduced plasma concentrations of pro-inflammatory cytokines TNF-alpha and IFN-gamma at 72 h. Rosuvastatin also induced a rapid and significant reduction of TNF-alpha and IFN-gamma production in stimulated T-lymphocytes at 72 h. When compared with placebo , rosuvastatin inhibited the Th-1-immune response measured at 72 h. CONCLUSION Rosuvastatin exerts rapid immunomodulatory effects on the level of T-cell activation in patients with ACS Background There are well-documented treatment gaps in secondary prevention of coronary heart disease and no clear guidelines to assist early physical activity after acute coronary syndromes ( ACS ) . Smartphone technology may provide an innovative platform to close these gaps . This paper describes the study design of a r and omized controlled trial assessing whether a smartphone-based secondary prevention program can facilitate early physical activity and improve cardiovascular health in patients with ACS . Methods We have developed a multi-faceted , patient-centred smartphone-based secondary prevention program emphasizing early physical activity with a graduated walking program initiated on discharge from ACS admission . The program incorporates ; physical activity tracking through the smartphone ’s accelerometer with interactive feedback and goal setting ; a dynamic dashboard to review and optimize cardiovascular risk factors ; educational messages delivered twice weekly ; a photographic food diary ; pharmacotherapy review ; and support through a short message service . The primary endpoint of the trial is change in exercise capacity , as measured by the change in six-minute walk test distance at 8-weeks when compared to baseline . Secondary endpoints include improvements in cardiovascular risk factor status , psychological well-being and quality of life , medication adherence , uptake of cardiac rehabilitation and re-hospitalizations . Discussion This r and omized controlled trial will use a smartphone-phone based secondary prevention program to emphasize early physical activity post-ACS . It will provide evidence regarding the feasibility and utility of this innovative platform in closing the treatment gaps in secondary prevention . Trial registration The trial was retrospectively registered in the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) on April 4 , 2016 . The registration number is ACTRN12616000426482 Background —The risk of ischemic events is high , both early and late after acute coronary syndromes ( ACS ) . We examine the benefits and risks associated with the use of adding clopidogrel to aspirin within the first 30 days and later ( 31 days to 12 months ) in 12 562 patients with ACS . Methods and Results —A total of 12 562 ACS patients were r and omized to receive clopidogrel ( 300 mg initially followed by 75 mg/d ) or placebo for 3 to 12 months . The proportion of patients experiencing cardiovascular death , myocardial infa rct ion , or strokes ( primary outcome ) at 30 days was 5.4 % in the placebo group and 4.3 % in the active group ( relative risk 0.79 , 95 % CI 0.67 to 0.92 ) . Beyond 30 days , the corresponding rates were 6.3 % versus 5.2 % ( relative risk 0.82 , 95 % CI 0.70 to 0.95 ) . There was no significant excess in life-threatening bleeds in each period ( 0.97 % versus 1.28 % , relative risk 1.32 , 95 % CI 0.95 to 1.84 for 0 to 30 days ; 0.83 % versus 0.91 % , relative risk 1.09 , 95 % CI 0.75 to 1.59 for 31 days to 12 months ) . Further subdivision of the early data indicates benefits within 24 hours with consistently lower rates of the primary outcome in combination with refractory or severe ischemia . Conclusions —Clopidogrel reduces the risk of ischemic vascular events , with the benefits emerging within 24 hours of initiation of treatment and continuing throughout the 12 months ( mean 9 months ) of the study BACKGROUND There are limited recent data on the prevalence and potentially different adverse impact of the various types of recurrent ischemia ( RI ) in unselected patients with acute coronary syndromes(ACS ) . We examined the clinical features and treatment associated with , and the differential prognostic impact of , the various types of RI in unselected patients across the broad spectrum of ACS in the contemporary era . METHODS The Global Registry of Acute Coronary Events ( GRACE ) was a prospect i ve , multinational registry of patients hospitalized for ACS . Data were collected on st and ardized case report forms . RESULTS Of the 29,400 ACS patients enrolled in May 2000-March 2007 , 21 % developed RI ; 2.4 % , 4.9 % , and 16 % had myocardial (re-)infa rct ion [ (re-)MI ] , RI with ST-segment changes , and RI without ST-segment changes ( not mutually exclusive ) , respectively . Rates of in-hospital mortality and complications , and 6-month mortality were significantly higher among patients with RI compared to those without ; the rates were highest for patients who developed (re-)MI , followed by those with RI and ST-segment changes . After adjusting for other vali date d prognosticators in the GRACE risk score , all three types of RI retained an independent association with both higher in-hospital and post-discharge 6-month mortality . Early revascularization was associated with lower in-hospital mortality only in the group with (re-)MI ( P for interaction=0.003 ) . CONCLUSIONS Despite the current use of intensive medical therapies , RI remains a common and serious consequence across the spectrum of ACS . Different types of RI confer a variable adverse prognostic impact . Re-MI is associated with the worst outcome , which appears to be mitigated by early revascularization . Our findings underscore the persistent need to improve the treatment of ACS Advances in antithrombotic therapy , along with an early invasive strategy , have reduced the incidence of recurrent ischemic events and death in patients with acute coronary syndromes ( ACS ; unstable angina , non – ST-segment – elevation myocardial infa rct ion [ MI ] , and ST-segment – elevation MI).1,–,4 However , the combination of multiple pharmacotherapies , including aspirin , platelet P2Y12 inhibitors , heparin plus glycoprotein IIb/IIIa inhibitors , direct thrombin inhibitors , and the increasing use of invasive procedures , has also been associated with an increased risk of bleeding . Editorial see p 2664 Bleeding complications have been associated with an increased risk of subsequent adverse outcomes , including MI , stroke , stent thrombosis , and death , in patients with ACS and in those undergoing percutaneous coronary intervention (PCI),5,–,10 as well as in the long-term antithrombotic setting .11,12 Thus , balancing the anti-ischemic benefits against the bleeding risk of antithrombotic agents and interventions is of paramount importance in assessing new therapies and in managing patients . Prior r and omized trials comparing antithrombotic agents suggest that a reduction in bleeding events is associated with improved survival.13,14 Because prevention of major bleeding may represent an important step in improving outcomes by balancing safety and efficacy in the contemporary treatment of ACS , bleeding events have been systematic ally identified as a crucial end point for the assessment of the safety of drugs during the course of r and omized clinical trials , and are an important aspect of the evaluation of new devices and interventional therapies.15 Unlike ischemic clinical events ( eg , cardiac death , MI , stent thrombosis ) , for which there is now general consensus on end-point definitions,16,17 there is substantial heterogeneity among the many bleeding definitions currently in use . Lack of st and ardization makes it difficult to optimally organize key clinical trial processes such as adjudication , and even more difficult to interpret relative OBJECTIVE To evaluate the incremental cost-effectiveness ratio ( ICER ) of switching to ezetimibe/simvastatin ( Eze/Simva ) compared with doubling the submaximal statin doses , in patients with acute coronary syndrome ( ACS ) events in the INFORCE study . METHODS Lifetime treatment costs and benefits were computed using a Markov model . Model inputs included each patient 's cardiovascular risk factor profile and actual lipid values at baseline and 12 weeks ( endpoint ) . Cardiovascular event and drug costs were discounted at 3.5 % . Age-specific utilities were based on UK literature values and non-coronary heart disease mortality rates on the Office of National Statistics data . In the INFORCE study , 384 patients taking statins at stable doses for ≥6 weeks before hospital admission were stratified by statin dose/potency ( low , medium , and high ) and then r and omized to doubling the statin dose or switching to Eze/Simva 10/40 mg for 12 weeks . RESULTS The Eze/Simva  group ( n=195 ) had a higher mean baseline total cholesterol than the double-statin group ( n=189 ) . Analyses were adjusted for baseline characteristics . In the INFORCE study , Eze/Simva  reduced low-density lipoprotein cholesterol ( LDL-C ) by ∼30 % ( vs. 4 % with doubling statin doses ) and significantly enhanced LDL-C goal attainment . In the cost-effectiveness analysis , Eze/Simva conferred 0.218 incremental discounted quality -adjusted life year ( QALY ) at a discounted incremental cost of £ 2524 , for an ICER of £ 11,571/QALY ( 95 % confidence interval=£8181-£18,600/QALY ) . The ICER was £ 13,552/QALY , £ 11,930/QALY , and £ 10,148/QALY in the low- , medium- , and high-potency strata , respectively . CONCLUSIONS Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment ( vs. double-statin ) in UK patients with ACS OBJECTIVES The purpose of this study was to determine if statins ( hydroxymethylglutaryl CoA reductase inhibitors [ HMG-CoA ] ) , angiotensin-converting enzyme ( ACE ) inhibitors , and angiotensin receptor blockers ( ARBs ) reduce cardiovascular ( CV ) events and pulmonary morbidity in chronic obstructive pulmonary disease ( COPD ) patients . BACKGROUND Few current COPD therapies alter prognosis . Although statins , ACE inhibitors , and ARBs improve outcomes in CV population s , their benefits in COPD patients both with and without concomitant heart disease has not previously been studied . METHODS A time-matched nested case-control study of two population -based retrospective cohorts was undertaken : 1 ) COPD patients having undergone coronary revascularization ( high CV risk cohort ) ; and 2 ) COPD patients without previous myocardial infa rct ion ( MI ) and newly treated with nonsteroidal anti-inflammatory drugs ( low CV risk cohort ) . Prespecified outcomes were COPD hospitalization , MI , and total mortality . RESULTS These drugs reduced both CV and pulmonary outcomes , with the largest benefits occurring with the combination of statins and either ACE inhibitors or ARBs . This combination was associated with a reduction in COPD hospitalization ( risk ratio [ RR ] 0.66 , 95 % confidence interval [ CI ] 0.51 to 0.85 ) and total mortality ( RR 0.42 , 95 % CI 0.33 to 0.52 ) not only in the high CV risk cohort but also in the low CV risk cohort ( RR 0.77 , 95 % CI 0.67 to 0.87 , and RR 0.36 , 95 % CI 0.28 to 0.45 , respectively ) . The combination also reduced MI in the high CV risk cohort ( RR 0.39 , 95 % CI 0.31 to 0.49 ) . Benefits were similar when steroid users were included . CONCLUSIONS These agents may have dual cardiopulmonary protective properties , thereby substantially altering prognosis of patients with COPD . These findings need confirmation in r and omized clinical trials Objective Takotsubo syndrome ( TS ) mimics acute coronary syndrome ( ACS ) but has a distinct pathophysiology . While in-hospital adverse outcomes appear similar to those presenting with an ACS , data on longer term postdischarge risk are conflicting . This study sought to assess the long-term prognosis of patients discharged alive after TS . Methods The clinical profile and in-hospital and long-term outcomes were prospect ively assessed in consecutive patients with TS . Survival in patients with TS was compared with two representative age-matched and gender-matched comparison cohorts : a hospitalised ACS cohort and a community cohort without known cardiovascular disease ( CVD ) . Results Two hundred and -twenty-five patients with TS ( 216 women , mean age 63.7±11.8 years ) were included . In-hospital mortality was 1.8 % and 1.9 % for patients with TS and ACS , respectively . Of the 219 patients with TS with postdischarge follow-up , at a mean follow-up of 4.8±3.2 years , there were 19 ( 8.3 % ) deaths , 18 of which were from non-cardiac causes . When compared with the cohort without prior CVD , postdischarge patients with TS were at increased mortality risk ( HR 2.00 , 95 % CI 1.26 to 3.17 , p=0.003 ) , but mortality in postdischarge patients with ACS was over threefold higher ( HR 3.43 , 95 % CI 2.97 to 3.96 , p<0.0001 ) . Conclusions In-hospital mortality for patients diagnosed with TS and ACS was similar . However , while postdischarge survivors of TS had a long-term survival which was poorer than for a community-based cohort without known CVD , their survival was better than for postdischarge survivors of an ACS event . Late deaths in patients with TS were almost all from non-cardiac causes Atrial fibrillation ( AF ) has been established as an independent predictor of long-term mortality after acute myocardial infa rct ion . However , this is less well defined across the whole spectrum of acute coronary syndromes ( ACSs ) . The Acute Coronary Syndrome Prospect i ve Audit is a prospect i ve multicenter registry with 12-month outcome data for 3,393 patients ( 755 with ST-segment elevation myocardial infa rct ion , 1942 with high-risk non-ST-segment elevation ACS [ NSTE-ACS ] , and 696 with intermediate-risk NSTE-ACS ) . A total of 149 patients ( 4.4 % ) had new-onset AF and 387 ( 11.4 % ) had previous AF .  New-onset AF was more , and previous AF was less frequent in those with ST-segment elevation myocardial infa rct ion than in those with high-risk NSTE-ACS or intermediate-risk NSTE-ACS ( p < 0.001 ) . Compared to patients without arrhythmia , patients with new-onset AF and previous AF were significantly older and had more high-risk features at presentation ( p < 0.004 ) . Patients with new-onset AF more often had left main coronary artery disease , result ing in a greater rate of surgical revascularization ( p < 0.001 ) . Only new-onset AF result ed in adverse in-hospital outcomes ( p < 0.001 ) . Only patients with previous AF had greater long-term mortality ( hazard ratio 1.42 , p < 0.05 ) . New-onset AF was only associated with a worse long-term composite outcome ( hazard ratio 1.66 , p = 0.004 ) . However , the odds ratio for the composite outcome was greatest for patients with new-onset AF with intermediate-risk NSTE-ACS ( odds ratio 3.9 , p = 0.02 ) than for those with high-risk NSTE-ACS ( odds ratio 2.0 , p = 0.01 ) or ST-segment elevation myocardial infa rct ion ( odds ratio 1.4 , p = 0.4 ) . In conclusion , new-onset AF was associated with worse short-term outcomes and previous AF was associated with greater mortality even at long-term follow-up . The prognostic burden of new-onset AF differed with the type of ACS presentation Background —In-hospital and postdischarge treatment rates for acute coronary syndrome ( ACS ) remain low in India . However , little is known about the prevalence and associations of the package of optimal ACS medical care in India . Our objective was to define the prevalence , associations , and impact of optimal in-hospital and discharge medical therapy in the Kerala ACS Registry of 25 718 admissions . Methods and Results —We defined optimal in-hospital ACS medical therapy as receiving the following 5 medications : aspirin , clopidogrel , heparin , & bgr;-blocker , and statin . We defined optimal discharge ACS medical therapy as receiving all of the above therapies except heparin . Comparisons by optimal versus nonoptimal ACS care were made via Student t test for continuous variables and & khgr;2 test for categorical variables . We created r and om effects logistic regression models to evaluate the association between Global Registry of Acute Coronary Events risk score variables and optimal in-hospital or discharge medical therapy . Optimal in-hospital and discharge medical care were delivered in 40 % and 46 % of admissions , respectively . Wide variability in both in-hospital and discharge medical care was present , with few hospitals reaching consistently high ( > 90 % ) levels . Patients receiving optimal in-hospital medical therapy had an adjusted odds ratio ( 95 % confidence interval)=0.93 ( 0.71 , 1.22 ) for in-hospital death and an adjusted odds ratio ( 95 % confidence interval)=0.79 ( 0.63 , 0.99 ) for major adverse cardiovascular event rates . Patients who received optimal in-hospital medical care were far more likely to receive optimal discharge care ( adjusted odds ratio [ 95 % confidence interval ] = 10.48 [ 9.37 , 11.72 ] ) . Conclusions —Strategies to improve in-hospital and discharge medical therapy are needed to improve local process-of-care measures and ACS outcomes in Kerala Atherosclerosis is currently considered a chronic inflammatory disease of the vessel wall . Systemic markers of inflammation have been shown to be of significant prognostic relevance for assessing the risk of atherosclerotic disease progression (1)(2)(3)(4 ) . Previous data showed that proinflammatory markers , such as C-reactive protein ( CRP ) , play an important role in acute coronary events (5)(6)(7 ) and that decreased plasma concentrations of antiinflammatory cytokines , for example , interleukin-10 ( IL-10 ) were also associated with acute coronary syndrome ( ACS ) (8)(9)(10 ) . Statins , 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors , represent a well-established class of drugs that effectively lower serum cholesterol concentrations and are widely used for the treatment of cardiovascular disease (11)(12)(13 ) . In addition to their cholesterol-lowering activity , statins have been demonstrated to possess pleiotropic effects , including antiinflammatory effects (14)(15)(16)(17 ) . Results obtained in numerous investigations have suggested that administration of statins could modify concentrations of CRP and other proinflammatory cytokines with a concurrent decrease in cardiovascular events . However , the potential influence of statins on the antiinflammatory cytokine IL-10 in patients with ACS has not been investigated . In the present study , 42 patients with unstable angina ( UA ) were r and omly assigned immediately after admission to st and ard therapy  plus either 20 mg/day atorvastatin or placebo . The st and ard therapy included aspirin , beta-blockers , heparin/low – molecular-weight heparin , angiotensin-converting enzyme inhibitors , and oral nitrates . The protocol s of the study were approved by the Ethics Review Board of the Hospital , and all patients gave written , informed consent . The patients with UA presented with  ischemic chest pain  at rest in the absence of extracardiac cause with ST-segment depression ≥0.1 mV in 2 or more contiguous leads on 12-lead electrocardiograms at administration . Echocardiography was performed in all patients to exclude patients with an impaired left OBJECTIVE To examine the relationship of baseline tissue plasminogen activator ( t-PA ) to early cardiovascular risk after an acute coronary syndrome , and the effect of intensive statin therapy . METHODS We measured plasma t-PA in 2860 of the 3086 ( 93 % ) subjects in the MIRACL study , an international r and omized trial of atorvastatin 80 mg daily versus placebo in patients with acute coronary syndromes . The relationship of t-PA to death , non-fatal acute myocardial infa rct ion , cardiac arrest , or worsening angina over 16 weeks was assessed by Cox Proportional Hazards . D-dimer was measured in a r and om sample of 395 subjects . RESULTS Higher baseline t-PA was significantly related to the risk of recurrent events ( HR=1.25 , p=0.0014 ) . This relationship was unaffected by adjustment for age , sex , troponin , hsCRP , and lipids ( HR=1.17 , p=0.029 ) , but was attenuated by adjustment including body mass index and smoking ( HR=1.14 , p=0.08 ) . D-dimer and t-PA concentrations were not related . Atorvastatin reduced the risk of recurrent events , but did not affect t-PA or D-dimer concentrations or the relationship of t-PA to outcomes . CONCLUSION In patients with acute coronary syndromes , increasing t-PA concentration was related to a higher early risk of recurrent events , paradoxically reflecting impaired endogenous fibrinolysis . This relationship is due in part to the association of t-PA with age , body mass index and smoking . Although statins lower the risk of recurrent events after acute coronary syndromes , it is unlikely that this benefit is achieved through thrombolytic and fibrinolytic pathways AIMS Elevated natriuretic peptides ( NPs ) are associated with an increased cardiovascular risk following acute coronary syndromes ( ACSs ) . However , the therapeutic implication s are still undefined . We hypothesized that early inhibition of renin-angiotensin-aldosterone system ( RAAS ) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo . METHODS AND RESULTS AVANT GARDE-TIMI 43 trial , a multinational , double-blind trial , r and omized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function < or=40 % but with an increased level of NP 3 - 10 days after admission to aliskiren , valsartan , their combination , and placebo .  The primary endpoint was the change in NT-proBNP from baseline to Week 8 . NT-proBNP declined significantly in each treatment arm , including placebo , by Week 8 , though there were no differences in the reduction between treatment strategies ( 42 % in placebo , 44 % in aliskiren , 39 % in valsartan , and 36 % in combination arm ) . Although several subgroups had higher baseline levels of NP and greater reductions over the study period , there were no differences among treatment groups in any subgroup . There were no differences in clinical outcomes but there were more adverse events , including serious events and adverse events leading to early study drug discontinuation , in patients treated with active therapy . CONCLUSION In this study of a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS , there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan , aliskiren , or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy . Moreover , adverse events were reported more frequently in patients assigned to active therapy CONTEXT Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome ( ACS ) event affect clinical outcome . OBJECTIVE To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS . DESIGN , SETTING , AND PARTICIPANTS International , r and omized , double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter ( n = 2265 ) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin ( n = 2232 ) , who were enrolled in phase Z of the A to Z trial between December 29 , 1999 , and January 6 , 2003 . MAIN OUTCOME MEASURE The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , readmission for ACS , and stroke . Follow-up was for at least 6 months and up to 24 months . RESULTS Among the patients in the placebo plus simvastatin group , the median low-density lipoprotein ( LDL ) cholesterol level achieved while taking placebo was 122 mg/dL ( 3.16 mmol/L ) at 1 month and was 77 mg/dL ( 1.99 mmol/L ) at 8 months while taking 20 mg/d of simvastatin . Among the patients in the simvastatin only group , the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL ( 1.76 mmol/L ) and was 63 mg/dL ( 1.63 mmol/L ) at 8 months while taking 80 mg/d of simvastatin . A total of 343 patients ( 16.7 % ) in the placebo plus simvastatin group experienced the primary end point compared with 309 ( 14.4 % ) in the simvastatin only group ( 40 mg/80 mg ) ( hazard ratio [ HR ] , 0.89 ; 95 % confidence interval [ CI ] 0.76 - 1.04 ; P = .14 ) . Cardiovascular death occurred in 109 ( 5.4 % ) and 83 ( 4.1 % ) patients in the 2 groups ( HR , 0.75 ; 95 % CI , 0.57 - 1.00 ; P = .05 ) but no differences were observed in other individual components of the primary end point . No difference was evident during the first 4 months between the groups for the primary end point ( HR , 1.01 ; 95 % CI , 0.83 - 1.25 ; P = .89 ) , but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group ( HR , 0.75 ; 95 % CI , 0.60 - 0.95 ; P = .02 ) . Myopathy ( creatine kinase > 10 times the upper limit of normal associated with muscle symptoms ) occurred in 9 patients ( 0.4 % ) receiving simvastatin 80 mg/d , in no patients receiving lower doses of simvastatin , and in 1 patient receiving placebo ( P = .02 ) . CONCLUSIONS The trial did not achieve the prespecified end point . However , among patients with ACS , the early initiation of an aggressive simvastatin regimen result ed in a favorable trend toward reduction of major cardiovascular events We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome ( ACS ) patients with low low-density lipoprotein ( LDL ) cholesterol level . One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study ( mean 78.2 ± 12.3 mg/dl ) . While 70 r and omly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their st and ard treatment as the atorvastatin group , the remaining 42 patients considered as the control group were given the st and ard treatment only , i.e. , without any lipid-lowering drug therapy .  Lipid profile , high-sensitivity C-reactive protein ( hsCRP ) , and plasma amyloid A ( SAA ) levels were measured in all patients within the first 24 h of chest pain , on the 5th day , and in the 6th month . During the inpatient period and subsequent 6-month follow-up , all episodes of angina , reinfa rct ion , revascularization , heart failure , rehospitalization , cardiac mortality , and total number of cardiac events were recorded . In the atorvastatin group , hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group ( P < 0.0001 ) . Mean LDL cholesterol level was significantly decreased in the atorvastatin group ( 55.7 ± 17.7 mg/dl ) , but there was no significant change in the control group at the 6th month . The frequency of heart failure during the inpatient period and angina , unstable angina pectoris , heart failure , and revascularization in the first 6 months were also significantly reduced in the atorvastatin group . Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels OBJECTIVES This study sought to evaluate the clinical relevance of potential clopidogrel drug-drug interactions . BACKGROUND Some studies have demonstrated that statins and calcium-channel blockers ( CCBs ) may attenuate the pharmacodynamic effects of clopidogrel . METHODS The TRITON-TIMI 38 ( Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infa rct ion 38 ) enrolled 13,608 patients with an acute coronary syndrome ( ACS ) and planned percutaneous coronary intervention ( PCI ) , and r and omized them to clopidogrel or prasugrel . Use of a statin or CCB was left to the discretion of the treating physician . A multivariable Cox model with propensity score was employed to evaluate the association between statin or CCB use and clinical outcomes . RESULTS Of the 6,795 subjects assigned to clopidogrel , 4,794 ( 70.6 % ) were on a CYP3A4-metabolized statin , and 966 ( 14.2 % ) were on a CCB at r and omization . The risk of cardiovascular ( CV ) death , myocardial infa rct ion ( MI ) , or stroke was similar regardless of baseline use of statins ( adjusted hazard ratio [ HR ] : 1.02 , 95 % confidence interval [ CI ] : 0.85 to 1.22 ) or CCBs ( adjusted HR : 1.16 ; 95 % CI : 0.94 to 1.43 ) in clopidogrel-treated patients . Further , the combined use of a CCB and atorvastatin 80 mg daily ( adjusted HR : 0.82 ; 95 % CI : 0.37 to 1.84 ) , or a CCB , statin , and proton pump inhibitor ( adjusted HR : 1.04 ; 95 % CI : 0.70 to 1.54 ) were not associated with an increased risk of CV death , MI , or stroke . The use of statins or CCBs did not modify the relative efficacy of prasugrel versus clopidogrel for the primary endpoint ( p for interaction = 0.43 , 0.55 , respectively ) . CONCLUSIONS In patients with ACS undergoing PCI , the use of statins or CCBs was not associated with an increased risk of CV events in clopidogrel-treated patients . Consistent results were observed when the drugs were administered alone , together , or in combination with proton pump inhibitors Background Observational studies have raised concerns that high‐potency statins increase the risk of acute kidney injury  . We therefore examined the incidence of kidney injury across 2 r and omized trials of statin therapy . Methods and Results PROVE IT‐TIMI 22 enrolled 4162 subjects after an acute coronary syndrome ( ACS ) and r and omized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day . A‐to‐Z enrolled 4497 subjects after ACS and r and omized them to a high‐potency ( simvastatin 40 mg/day × 1 months , then simvastatin 80 mg/day ) versus a delayed moderate‐potency statin strategy ( placebo × 4 months , then simvastatin 20 mg/day ) . Serum creatinine was assessed central ly at serial time points . Adverse events ( AEs ) relating to kidney injury were identified through data base review . Across both trials , mean serum creatinine was similar between treatment arms at baseline and throughout follow‐up . In A‐to‐Z , the incidence of a 1.5‐fold or ≥0.3 mg/dL rise in serum creatinine was 11.4 % for subjects r and omized to a high‐potency statin regimen versus 12.4 % for those on a delayed moderate‐potency regimen ( odds ratio [ OR ] , 0.91 ; 95 % confidence interval [ CI ] , 0.76 to 1.10 ; P=0.33 ) . In PROVE IT‐TIMI 22 , the incidence was 9.4 % for subjects r and omized to atorvastatin 80 mg/day and 10.6 % for subjects r and omized to pravastatin 40 mg/day ( OR , 0.88 ; 95 % CI , 0.71 to 1.09 ; P=0.25 ) . Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction . The incidence of kidney injury‐related adverse events ( AEs ) was not statistically different for patients on a high‐potency versus moderate‐potency statin regimen ( OR , 1.06 ; 95 % CI , 0.68 to 1.67 ; P=0.78 ) . Conclusions For patients enrolled in 2 large r and omized trials of statin therapy after ACS , the use of a high‐potency statin regimen did not increase the risk of kidney injury BACKGROUND The ICTUS trial was a study that compared an early invasive with a selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome ( nSTE-ACS ) . The study reported no difference between the strategies for frequency of death , myocardial infa rct ion , or rehospitalisation after 1 year . We did a follow-up study to assess the effects of these treatment strategies after 4 years . METHODS 1200 patients with nSTE-ACS and an elevated cardiac troponin were enrolled from 42 hospitals in the Netherl and s. Patients were r and omly assigned either to an early invasive strategy , including early routine catheterisation and revascularisation where appropriate , or to a more selective invasive strategy , where catheterisation was done if the patient had refractory angina or recurrent ischaemia . The main endpoints for the current follow-up study were death , recurrent myocardial infa rct ion , or rehospitalisation for anginal symptoms within 3 years after r and omisation , and cardiovascular mortality and all-cause mortality within 4 years . Analysis was by intention-to-treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N82153174 . FINDINGS The in-hospital revascularisation rate was 76 % in the early invasive group and 40 % in the selective invasive group . After 3 years , the cumulative rate for the combined endpoint was 30.0 % in the early invasive group compared with 26.0 % in the selective invasive group ( hazard ratio 1.21 ; 95 % CI 0.97 - 1.50 ; p=0.09 ) . Myocardial infa rct ion was more frequent in the early invasive strategy group ( 106 [ 18.3 % ] vs 69 [ 12.3 % ] ; HR 1.61 ; 1.19 - 2.18 ; p=0.002 ) . Rates of death or spontaneous myocardial infa rct ion were not different ( 76 [ 14.3 % ] patients in the early invasive and 63 [ 11.2 % ] patients in the selective invasive strategy [ HR 1.19 ; 0.86 - 1.67 ; p=0.30 ] ) . No difference in all-cause mortality ( 7.9%vs 7.7 % ; p=0.62 ) or cardiovascular mortality ( 4.5%vs 5.0 % ; p=0.97 ) was seen within 4 years . INTERPRETATION Long-term follow-up of the ICTUS trial suggests that an early invasive strategy might not be better than a more selective invasive strategy in patients with nSTE-ACS and an elevated cardiac troponin , and implementation of either strategy might be acceptable in these patients R and omized controlled trials support the use of an early invasive strategy in high-risk patients with non-ST-segment elevation ( NSTE ) acute coronary syndromes ( ACS ) . Although risk increases with age , limited data are available to support this strategy in older patients . The aims of this study were to examine temporal trends in the management and outcomes of NSTE ACS in elderly patients and to explore reasons for the lower use of early angiography in the aged population . Data from 11,732 patients with NSTE ACS were collected from 3 consecutive Canadian registries ( ACS I , ACS II , and Global Registry of Acute Coronary Events [GRACE]/GRACE2 ) from 1999 to 2007 . Rates of in-hospital cardiac catheterization , revascularization , infa rct ion or reinfa rct ion , and death were stratified by age ( < 65 , 65 to 74 , and > or = 75 years ) . Although overall , rates of in-hospital catheterization and revascularization increased over time ( p < 0.001 ) , the largest increase occurred in patients aged < 65 years . The strongest independent negative predictor of the use of cardiac catheterization was age > or = 75 years ( adjusted odds ratio 0.45 , 95 % confidence interval 0.37 to 0.56 , p < 0.001 ) . Use of an early invasive approach was associated with a reduction in 1-year mortality across all age groups , but the absolute difference was greatest in patients aged > or = 75 years . The underestimation of risk by physicians ( ascertained in ACS II ) was the most common reason for choosing a conservative strategy . In conclusion , despite an overall increased use of an early invasive strategy , elderly patients with NSTE ACS remain significantly less likely to undergo cardiac catheterization and revascularization and are often erroneously perceived to be at low risk by their physicians . Future studies should determine whether more aggressive treatment of these high-risk elderly patients improves outcomes Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention ( PCI ) . However , the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome ( ACS ) undergoing PCI has not been established and represents the objective of this investigation . On-treatment P2Y12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein ( VASP ) phosphorylation assay before PCI , at hospital discharge , and at 1 month after PCI in ACS patients enrolled in the multicenter , prospect i ve GEne polymorphisms , Platelet Reactivity , and Syntax Score ( GEPRESS ) study ( n = 962 ) .  High platelet reactivity ( HPR ) was defined as platelet reactivity index ≥50 % . Statins were prescribed at hospital discharge in 87 % ( n = 835 ) of patients . All patients were followed for 1 year . The 1-month HPR rate was lower in statin than in non-statin treated patients ( 39.6 vs 52 % , respectively , p = 0.009 ) . This finding was confirmed also among statin-treated patients with high Syntax score ( ≥15 ) . After adjustment for differences in baseline characteristics , statin use at discharge was independently associated with 1-month HPR rate ( odds ratio , 0.58 , 95 % confidence interval , 0.38–0.89 ; p = 0.015 ) . In ACS patients undergoing PCI  treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins Introduction Data suggest that the beneficial cardiovascular effects of statins are maximized after the first year of statin use ; yet , the timeline of statin-associated adverse events is not well delineated . Objective To examine the associations of short-term statin use ( ≤1 year ) with short- and long-term adverse events and beneficial cardiovascular outcomes in a ‘ healthy ’ cohort . Participants and Methods A cohort study of a healthy Tricare population ( fiscal year [ FY ] 2002 through FY 2011 ) who have no cardiovascular disease , major comorbidities requiring medications , or functional limitations . Statin users used statins for 90–365 days during FY 2005 as their only prescription medication . Nonusers had medical encounters but did not receive prescription medications during FY 2005 , and did not receive any statins throughout the study period from FY 2002 to FY 2011 . Outcomes were the occurrence of major acute cardiovascular events , diabetes mellitus and its complications , kidney diseases , musculoskeletal diseases , obesity , cataracts , malignancy , and death . Results We matched 1525 statin users to 1525 nonusers . During the follow-up period ( FY 2006 to FY 2011 ) , statin users had significantly higher odds of developing diabetes and diabetic complications that persisted throughout follow-up ( odds ratio [ OR ] 1.93 , 95 % confidence interval [ CI ] 1.55–2.41 and OR 2.15 , 95 % CI 1.20–3.86 , respectively ) . Short-term statin use was not associated with decreased odds of major acute cardiovascular events ( OR 1.17 , 95 % CI 0.72–1.92 ) . There were no differences in risks of kidney diseases , musculoskeletal diseases , or malignancy . Conclusions Short-term statin use for primary prevention in this healthy cohort was associated with an increased risk of long-term diabetes and diabetic complications without cardiovascular benefits . Further study using pragmatic studies and prospect i ve observational studies appropriately equipped to eliminate unidentified confounders are urgently needed OBJECTIVES The aim of the present study was to evaluate whether the effect of an early invasive treatment strategy differed between patients sub-grouped according to their severity of myocardial ischemia , as evaluated by quantitative electrocardiographic ( ECG ) analysis at the time of presentation . The present study is a sub- study of the previously published Fast Revascularization during InStability in Coronary artery disease trial ( FRISC-II ) . BACKGROUND An early invasive treatment strategy has been shown to be the preferable treatment for non-ST-segment elevation acute coronary syndromes ( ACS ) . The population of patients with unstable coronary artery disease is heterogeneous regarding both the underlying pathology and prognosis . Early risk stratification is important to select patient subgroups that will benefit the most from a given treatment . METHODS In 2,201 patients with non-ST-segment elevation ACS , the ischemic burden at hospital admission was determined by quantitative measurements of ST-T-segment deviations on the ECG . The patients were subsequently sub-grouped in tertiles based on the amount of ST-segment deviation . The primary end point for this analysis was death or myocardial infa rct ion ( MI ) within one year after study inclusion . RESULTS The invasive treatment strategy produced a reduction of approximately 50 % in death or MI among the patients with intermediate or major ST-segment deviation . The findings were independent of age , gender , or troponin T status . The patients with confounding factors precluding ST analysis had a poor outcome regardless of the treatment strategy . CONCLUSIONS Ischemic burden on the admission ECG identifies patients with ACS who benefit the most from an invasive treatment strategy . When the st and ard ECG is scrutinized with complete quantitative measurements , it provides independent information on prognosis and benefit of treatment BACKGROUND Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes ( ACS ) . The type , outcome , and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported . METHODS We evaluated stroke incidence , subtypes , and outcomes , in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes ( SYMPHONY ) and 2nd SYMPHONY trials . RESULTS Of 15,904 stabilized patients with ACS , 113 ( 0.71 % ) had a stroke over a median follow-up of 90 days . The majority of strokes occurred within 30 days of presentation , and the time course for stroke occurrence paralleled that of myocardial (re)infa rct ion . Most strokes were ischemic ( 78 % ) , and 52 % result ed in moderate or severe disability or death . Patients with stroke were older and more often had hypertension , diabetes , peripheral vascular disease , and atrial fibrillation . Among patients with stroke who had cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass grafting , stroke occurred predominantly after the procedure . No difference in occurrence or type of stroke was observed in the assigned treatment groups . In multivariable modeling age , heart failure , prior stroke , left bundle branch block , and systolic blood pressure predicted the occurrence of stroke . CONCLUSIONS In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and  /or aspirin  , stroke occurred in fewer than 1 % within 90 days but carried a significant mortality and morbidity risk AIMS Acute coronary syndromes ( ACS ) are mostly caused by plaque rupture . This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound ( IVUS ) in patients undergoing coronary angiography .  METHODS AND RESULTS Between November 2008 and January 2011 , IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS ( n = 318 ) or stable angina ( n = 263 ) . Primary endpoint was major adverse cardiac events ( MACEs ) defined as mortality , ACS , or unplanned coronary revascularization . Culprit lesion-related events were not counted . Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8 % . The presence of IVUS virtual histology-derived thin-cap fibroatheroma ( TCFA ) lesions ( present 10.8 % vs. absent 5.6 % ; adjusted HR : 1.98 , 95 % CI : 1.09 - 3.60 ; P = 0.026 ) and lesions with a plaque burden of ≥70 % ( present 16.2 % vs. absent 5.5 % ; adjusted HR : 2.90 , 95 % CI : 1.60 - 5.25 ; P < 0.001 ) were independently associated with a higher MACE rate . Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only ( present 7.5 % vs. absent 3.0 % ; adjusted HR : 2.51 , 95 % CI : 1.15 - 5.49 ; P = 0.021 ) . Thin-cap fibroatheroma lesions with a plaque burden of ≥70 % were associated with a higher MACE rate within ( P = 0.011 ) and after ( P < 0.001 ) 6 months of follow-up , while smaller TCFA lesions were only associated with a higher MACE rate after 6 months ( P = 0.033 ) . CONCLUSION In patients undergoing coronary angiography  , the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year , particularly of death and ACS . Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions , especially on the short term CONTEXT Depression observed following acute coronary syndrome ( ACS ) is common and associated with an increased risk of death . The Sertraline Antidepressant Heart Attack Trial ( SADHART ) tested the safety and efficacy of a selective serotonin reuptake inhibitor in this population . No evidence of harm was seen , and sertraline hydrochloride had an overall beneficial effect on mood that occurred primarily in patients with a history of episodes of major depressive disorder ( MDD ) . OBJECTIVES To determine how frequently the MDD began before ACS and whether onset of the current MDD episode before or after the ACS event influenced response to sertraline . DESIGN , SETTING S , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled treatment of 369 patients with ACS and MDD was conducted in 40 outpatient clinics in 10 countries between April 1 , 1997 , and April 30 , 2001 . MAIN OUTCOME MEASURES Diagnosis of MDD , number of previous episodes of depression , and episode onset before or after hospitalization were established using the Diagnostic Interview Schedule . Treatment response was measured with the Clinical Global Impression-Improvement scale . RESULTS Fifty-three percent of MDD episodes began before hospitalization for the index episode of ACS ( for 197 of 369 patients ) , and 94 % of the MDD episodes began more than 30 days before the index ACS episode . Episodes of MDD that began prior to ACS responded more frequently to sertraline than to placebo ( 63 % vs 46 % , respectively ; odds ratio , 2.0 ; 95 % confidence interval , 1.13 - 3.55 ) whereas depression with onset beginning after hospitalization showed a high placebo  response rate ( 69 % vs 60 % , respectively ) and low sertraline-placebo response ratio ( 1.15 ) . Multivariate analysis indicated that time of onset of the current episode , history of MDD , and baseline severity independently predicted the sertraline-placebo response ratio . CONCLUSIONS Half of the episodes of major depression associated with ACS began long before ACS and therefore were not caused by ACS . Patients whose current episodes of MDD begin before ACS , those with a history of MDD , and those whose episodes are severe should be treated because they will benefit considerably from sertraline . Since these 3 predictors of sertraline response are independent , having more than 1 of them substantially increases the benefit of sertraline while reducing the chance of spontaneous recovery BACKGROUND Reduction in low-density lipoprotein cholesterol ( LDL-C ) improves clinical outcomes in patients with chronic coronary artery disease and acute coronary syndromes ( ACSs ) . The combination of ezetimibe/simvastatin produces greater reductions in LDL-C compared to simvastatin monotherapy . The IMProved Reduction of Outcomes : Vytorin Efficacy International Trial ( IMPROVE-IT ) is a multicenter , r and omized , double-blind , active-control trial design ed to test the hypothesis that the addition of ezetimibe to statin therapy , using ezetimibe/simvastatin , will translate into increased clinical benefit on cardiovascular outcomes relative to simvastatin monotherapy in patients with ACS . STUDY DESIGN The study will recruit up to 18,000 moderate- to high-risk patients stabilized after ACS . Patients are r and omized in a 1:1 ratio to once-daily doses of either ezetimibe/simvastatin 10/40 mg or simvastatin monotherapy 40 mg . Follow-up visits are at 1 and 4 months , and every 4 months thereafter . If consecutive measures of LDL-C are > 79 mg/dL at follow-up visits , the simvastatin dose will be increased to 80 mg in a double-blind manner . The primary end point is the first occurrence of cardiovascular death , nonfatal myocardial infa rct ion , rehospitalization for unstable angina , coronary revascularization ( occurring at least 30 days after r and omization ) , or stroke . Patients will be followed for a minimum of 2.5 years and until at least 5,250 patients experience a primary end point . SUMMARY IMPROVE-IT will determine whether the addition of ezetimibe to statin therapy , using ezetimibe/simvastatin , improves cardiovascular outcomes compared with simvastatin monotherapy in patients after ACS . In addition , the difference in achieved LDL-C levels between the groups will provide data on whether the target for LDL-C lowering should be reduced further BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either  tr and olapril  at a target dose of  4 mg  per  day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving " current st and ard " therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization Background —Few data are available on the impact of heart failure ( HF ) across all types of acute coronary syndromes ( ACS ) . Methods and Results —The Global Registry of Acute Coronary Events ( GRACE ) is a prospect i ve study of patients hospitalized with ACS . Data from 16 166 patients were analyzed : 13 707 patients without prior HF or cardiogenic shock at presentation were identified . Of these , 1778 ( 13 % ) had an admission diagnosis of HF ( Killip class II or III ) . HF on admission was associated with a marked increase in mortality rates during hospitalization ( 12.0 % versus 2.9 % [ with versus without HF ] , P < 0.0001 ) and at 6 months after discharge ( 8.5 % versus 2.8 % , P < 0.0001 ) . Of note , HF increased mortality rates in patients with unstable angina ( defined as ACS with normal biochemical markers of necrosis ; mortality rates : 6.7 % with versus 1.6 % without HF at admission , P < 0.0001 ) . By logistic regression analysis , admission HF was an independent predictor of hospital death ( odds ratio , 2.2 ; P < 0.0001 ) . Admission HF was associated with longer hospital stay and higher readmission rates .  Patients with HF had lower rates of catheterization and percutaneous cardiac intervention , and fewer received & bgr;-blockers and statins . Hospital development of HF ( versus HF on presentation ) was associated with an even higher in-hospital mortality rate ( 17.8 % versus 12.0 % , P < 0.0001 ) . In patients with HF , in-hospital revascularization was associated with lower 6-month death rates ( 14.0 % versus 23.7 % , P < 0.0001 ; adjusted hazard ratio , 0.5 ; 95 % CI , 0.37 to 0.68 , P < 0.0001 ) . Conclusions —In this observational registry , heart failure was associated with reduced hospital and 6-month survival across all ACS subsets , including patients with normal markers of necrosis . More aggressive treatment of these patients may be warranted to improve prognosis BACKGROUND Renal impairment is strongly linked to adverse cardiovascular ( CV ) events . Baseline renal dysfunction is a strong predictor of CV mortality and morbidity in patients admitted with acute coronary syndrome ( ACS ) . However , the prognostic importance of worsening renal function ( WRF ) in these patients is not well characterized . METHODS ACS patients enrolled in the SPACE ( Saudi Project for Assessment of Coronary Events ) registry who had baseline and pre-discharge serum creatinine data available were eligible for this study . WRF was defined as a 25 % reduction from admission estimated glomerular filtration rate ( eGFR ) within 7 days of hospitalization . Baseline demographics , clinical presentation , therapies , and in-hospital outcomes were compared . RESULTS Of the 3583 ACS patients , WRF occurred in 225 patients ( 6.3 % ) , who were older , had more cardiovascular risk factors , were more likely to be female , have past vascular disease , and presented with more non-ST-segment elevation myocardial infa rct ion than patients without WRF ( 39.5 % vs. 32.8 % ; p=0.042 ) . WRF was associated with an increased risk of in-hospital death , heart failure , cardiogenic shock , and stroke . After adjusting for potential confounders , WRF was an independent predictor of in-hospital death ( adjusted odd ratio 28.02 , 95 % CI 13.2 - 60.28 , p<0.0001 ) . WRF was more predictive of mortality than baseline eGFR . CONCLUSION These results indicate that WRF is a powerful predictor for in-hospital mortality and CV complications in ACS patients Therapy with individual 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) has been shown conclusively to diminish coronary event rates and mortality in both primary and secondary prevention . To date , scant attention has been paid to whether initiation of such regimens in the hospital phase of acute coronary syndromes might confer cardioprotective benefits . The purpose of this study was to determine the safety and tolerability of early initiation of statin therapy in patients with acute coronary syndromes . In this r and omised , double-blind , three-month , pilot study , 100 patients with acute myocardial infa rct ion or unstable angina and low-density lipoprotein cholesterol > 3.5 mmol/l were r and omly assigned to pravastatin 40 mg daily or placebo initiated within 48 hours of hospital admission . Pravastatin proved safe and well tolerated in these patients , who were well matched at baseline . No statistically significant differences in death , MI and drug-related adverse events were observed in the pravastatin group compared with control subjects . This pilot study shows that therapy with pravastatin early after an acute coronary event is safe and well tolerated . Larger , long-term studies are needed to confirm these findings BACKGROUND Although most cardiovascular disease occurs in low-income and middle-income countries , little is known about the use of effective secondary prevention medications in these communities . We aim ed to assess use of proven effective secondary preventive drugs ( antiplatelet drugs , β blockers , angiotensin-converting-enzyme [ ACE ] inhibitors or angiotensin-receptor blockers [ ARBs ] , and statins ) in individuals with a history of coronary heart disease or stroke . METHODS In the Prospect i ve Urban Rural Epidemiological ( PURE ) study , we recruited individuals aged 35 - 70 years from rural and urban communities in countries at various stages of economic development . We assessed rates of previous cardiovascular disease ( coronary heart disease or stroke ) and use of proven effective  secondary preventive drugs  and blood-pressure-lowering drugs with st and ardised question naires , which were completed by telephone interviews , household visits , or on patient 's presentation to clinics . We report estimates of drug use at national , community , and individual levels . FINDINGS We enrolled 153,996 adults from 628 urban and rural communities in countries with incomes classified as high ( three countries ) , upper-middle ( seven ) , lower-middle ( three ) , or low ( four ) between January , 2003 , and December , 2009 . 5650 participants had a self-reported coronary heart disease event ( median 5·0 years previously [ IQR 2·0 - 10·0 ] ) and 2292 had stroke ( 4·0 years previously [ 2·0 - 8·0 ] ) . Overall , few individuals with cardiovascular disease took antiplatelet drugs  ( 25·3 % ) , β blockers ( 17·4 % ) , ACE inhibitors or ARBs ( 19·5 % ) , or statins ( 14·6 % ) . Use was highest in high-income countries ( antiplatelet drugs 62·0 % , β blockers 40·0 % , ACE inhibitors or ARBs 49·8 % , and statins 66·5 % ) , lowest in low-income countries ( 8·8 % , 9·7 % , 5·2 % , and 3·3 % , respectively ) , and decreased in line with reduction of country economic status ( p(trend)<0·0001 for every drug type ) . Fewest patients received no drugs in high-income countries ( 11·2 % ) , compared with 45·1 % in upper middle-income countries , 69·3 % in lower middle-income countries , and 80·2 % in low-income countries . Drug use was higher in urban than rural areas ( antiplatelet drugs 28·7 % urban vs 21·3 % rural , β blockers 23·5%vs 15·6 % , ACE inhibitors or ARBs 22·8%vs 15·5 % , and statins 19·9%vs 11·6 % ; all p<0·0001 ) , with greatest variation in poorest countries ( p(interaction)<0·0001 for urban vs rural differences by country economic status ) . Country-level factors ( eg , economic status ) affected rates of drug use more than did individual-level factors ( eg , age , sex , education , smoking status , body-mass index , and hypertension and diabetes statuses ) . INTERPRETATION Because use of secondary prevention medications is low worldwide-especially in low-income countries and rural areas - systematic approaches are needed to improve the long-term use of basic , inexpensive , and effective drugs . FUNDING Full funding sources listed at end of paper ( see Acknowledgments )
Based on moderate quality evidence , due to concerns about risk of bias and imprecision , initiation of statin therapy within 14 days following ACS does not reduce death , myocardial infa rct ion , or stroke up to four months , but reduces the occurrence of unstable angina at four months following ACS .
Serious side effects were rare
BACKGROUND The early period following the onset of acute coronary syndrome ( ACS ) represents a critical stage of coronary heart disease , with a high risk of recurrent events and deaths .
The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear .
This is an up date of a review previously published in 2011 .
OBJECTIVES To assess the effects , both harms and benefits , of early administered statins in patients with ACS , in terms of mortality and cardiovascular events .