Selection for Coronary Angiography In contrast to noninvasive tests, coronary angiography provides detailed structural information for assessment of prognosis and appropriate management. When combined with LV angi- ography, it also provides an assessment of global and regional LV function. Coronary angiography is usually indicated in patients with NSTE-ACS who have recurrent symptoms or ischemia despite adequate medical therapy or who are at high risk as categorized by clinical findings (HF, serious ventricular arrhythmias), noninvasive test findings (significant LV dysfunc- tion with EF <0.40, large anterior or multiple perfusion defects or wall motion abnormalities on echocardiography, high-risk Duke treadmill score 11), high-risk TIMI or GRACE scores, or markedly elevated troponin levels. Patients with NSTE-ACS who have had previous PCI or CABG should also be considered for early coronary angiography, unless prior coronary angiog- raphy data indicate that no further revascularization is feasible. The general indications for coronary angiography and revascularization should be tempered by individual patient characteristics and preferences (a patient-centered approach). Patient and clinician judgments about risks and benefits are important for patients who might not be candidates for cor- onary revascularization, such as very frail older adults and those with serious comorbid conditions (eg, severe hepatic, pulmonary, or renal failure; active or inoperable cancer). See Online Data Supplement 20 for additional information on risk stratification. 5. Myocardial Revascularization Recommendations about coronary artery revascularization indications, benefits, and choice of revascularization proce- dure (PCI or CABG) for all anatomic subsets have been pub- lished in the 2011 PCI CPG,26 and the 2012 stable ischemic heart disease CPG and its 2014 focused The main difference between management of patients with stable ischemic heart disease and NSTE-ACS is a stronger impetus for revascularization in those with NSTE- ACS. Myocardial ischemia in ACS may progress to MI and is potentially life threatening.


Myocardial ischemia in ACS may progress to MI and is potentially life threatening. In addition, in patients with ACS, angina (including recurrent angina) is more likely to be reduced by revascularization than by medical therapy.26 A heart team approach to revascularization deci- sions, involving an interventional cardiologist and cardio- thoracic surgeon, is used in patients with unprotected left main or complex CAD. Calculation of SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) and STS scores is reasonable in these patients to guide the choice of revascularization.23,26,355 Factors that influence the choice of revascularization pro- cedure include the extent and complexity of CAD; short-term risk and long-term durability of PCI; operative mortality (which can be estimated by the STS score); diabetes mellitus; CKD; completeness of revascularization; LV systolic dys- function; previous CABG; and the ability of the patient to tol- erate and comply with DAPT. In general, the greater the extent and complexity of the multivessel disease, the more com- pelling the choice of CABG over multivessel PCI.23,26,356 358 In patients with NSTE-ACS, PCI of a culprit unprotected left main coronary artery lesion is an option if the patient is not a candidate for CABG.23,26 See Online Data Supplements 21 and 22 for additional information on myocardial revascularization. 5.1. Percutaneous Coronary Intervention 5.1.1. PCI General Considerations: Recommendation Class IIb 1.


Percutaneous Coronary Intervention 5.1.1. PCI General Considerations: Recommendation Class IIb 1. A strategy of multivessel PCI, in contrast to cul- prit lesion only PCI, may be reasonable in pa- tients undergoing coronary revascularization as part of treatment for NSTE-ACS.330,359 364 (Level of Evidence: B) Approximately half of all PCI procedures are performed in patients with UA or NSTEMI, and approximately 32% to 40% of patients with NSTE-ACS will undergo PCI.365 As discussed previously, in patients with NSTE-ACS, a strategy of early angiography and revascularization (primarily with PCI) results in lower rates of recurrent UA, recurrent reho- spitalization, MI, and death.366,367 Although PCI of a noncul- prit lesion is not advocated in patients with STEMI,26 there is less agreement on whether nonculprit lesions should undergo intervention at the time of culprit-lesion PCI for NSTE-ACS. but not all,330 comparing culprit lesion only PCI with multivessel PCI (eg, PCI of multiple vessels performed at the same time) in patients with NSTE-ACS did not find an increased risk of MACE with multivessel PCI and found a reduction in the need for repeat revascularization. However, the data consist predominantly of post hoc analysis of nonrandomized data with variable duration of follow-up. This question has not been resolved and is an area of current investigation. 5.1.2. PCI Antiplatelet and Anticoagulant Therapy 5.1.2.1. Oral and Intravenous Antiplatelet Agents: Recommendations Class I 1. Patients already taking daily aspirin before PCI should take 81 mg to 325 mg non enteric-coated as- pirin before PCI.26,368 370 (Level of Evidence: B) 2. Patients not on aspirin therapy should be given non enteric- coated aspirin 325 mg as soon as possible be- (Level of Evidence: B) 3.


Patients not on aspirin therapy should be given non enteric- coated aspirin 325 mg as soon as possible be- (Level of Evidence: B) 3. After PCI, aspirin should be continued indefinitely at a dose of 81 mg to 325 mg daily.27,288,371 (Level of Evidence: B) Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e373 4. A loading dose of a P2Y12 receptor inhibitor should be given before the procedure in patients undergoing PCI with stenting.26,293,302,331,372 375 (Level of Evidence:A) Options include: (Level of Evidence: B) or (Level of Evidence: B) or (Level of Evidence: B) 5. In patients with NSTE-ACS and high-risk features (eg, elevated troponin) not adequately pretreated with clopidogrel or ticagrelor, it is useful to adminis- ter a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time (Level of Evidence: A) 6. In patients receiving a stent (bare-metal stent or drug-eluting stent [DES]) during PCI for NSTE- inhibitor therapy should be given for at Options include: a. (Level of Evidence: B) or b. Prasugrel#: 10 mg daily302 (Level of Evidence: B) or c. Ticagrelor : 90 mg twice daily293 (Level of Evidence: B) Class IIa 1. It is reasonable to choose ticagrelor over clopido- grel for P2Y12 inhibition treatment in patients with NSTE-ACS treated with an early invasive strategy and/or coronary stenting.293,294 (Level of Evidence: B) 2. It is reasonable to choose prasugrel over clopidogrel treatment in patients with NSTE-ACS who undergo PCI who are not at high risk of bleeding (Level of Evidence: B) 3. In patients with NSTE-ACS and high-risk features (eg, elevated troponin) treated with UFH and ad- equately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofi- ban) at the time of PCI.195,383,384 (Level of Evidence: B) 4.


In patients with NSTE-ACS and high-risk features (eg, elevated troponin) treated with UFH and ad- equately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofi- ban) at the time of PCI.195,383,384 (Level of Evidence: B) 4. After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance dos- (Level of Evidence: B) 5. If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of inhibitor therapy after stent implantation, ear- lier discontinuation (eg, <12 months) of P2Y12 inhibi- tor therapy is reasonable.330 (Level of Evidence: C) Class IIb 1. Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implanta- tion. (Level of Evidence: C) Class III: Harm 1.


Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implanta- tion. (Level of Evidence: C) Class III: Harm 1. Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic (Level of Evidence: B) Comprehensive recommendations on the use of antiplatelet and anticoagulant therapy in patients with NSTE-ACS under- going PCI are given in the 2011 PCI CPG.26 Aspirin reduces the frequency of ischemic complications after PCI and is ideally administered at least 2 hours, and preferably 24 hours, before DAPT, consisting of aspirin and a P2Y12 inhibitor, in patients treated with coronary stents reduces the risk of stent thrombosis and composite ischemic events.296,331,372 375,389,390 Compared with a loading dose of 300 mg of clopidogrel, a load- ing dose of 600 mg of clopidogrel in patients undergoing PCI achieves greater platelet inhibition with fewer low responders and decreases the incidence of MACE.376 378 In patients with ACS who have undergone coronary stenting, treatment with prasugrel or ticagrelor, compared with treatment with clopi- dogrel, results in a greater reduction in composite ischemic events and the incidence of stent thrombosis, although at a risk of increased non CABG bleeding.293,302 The optimal dura- tion of DAPT therapy in patients treated with DES is not well However, aspirin is continued indefinitely in all patients managed with a bare-metal stent or DES, and DAPT is an option for >12 months in patients who have received a DES. This determination should balance the risks of stent thrombo- sis and ischemic complications versus bleeding and should be jointly made by the clinician and the patient.


This determination should balance the risks of stent thrombo- sis and ischemic complications versus bleeding and should be jointly made by the clinician and the patient. Loading and short-term maintenance doses of clopi- dogrel were studied in CURRENT OASIS (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events Organization to Assess Strategies in Ischemic Syndromes) 7, which demonstrated a potential benefit of higher-dose clopidogrel (600-mg loading dose, 150 mg daily for 6 days, 75 mg daily thereafter) in patients with NSTE-ACS under- going an invasive management strategy.292,391 Although the failed to demonstrate a significant difference in the primary endpoint between the clopidogrel and aspirin groups (4.2% versus 4.4%), the PCI subset (n=17263) showed significant differences in the clopidogrel arm.391 Notably, the higher-dose clopidogrel therapy increased major bleeding in the entire group (2.5% versus 2.0%; P=0.012) and the PCI subgroup (1.1% versus 0.7%; P=0.008). In addition, during the period of several hours required for conversion of clopi- dogrel to its active metabolite, there is reduced effectiveness. However, efficacy is restored following conversion. Patients undergoing PCI who have previously received a loading dose of 300 mg of clopidogrel and are on a 75-mg daily maintenance dose should receive another 300-mg There are no data appropriate for prasugrel because this drug is administered before PCI. For ticagrelor, there are no data on additional loading. 5.1.2.2. GP IIb/IIIa Inhibitors: Recommendations Class I 1. In patients with NSTE-ACS and high-risk features (eg, elevated troponin) who are not adequately pretreated #Patients should receive a loading dose of prasugrel, provided that they were not pretreated with another P2Y12 receptor inhibitor.


In patients with NSTE-ACS and high-risk features (eg, elevated troponin) who are not adequately pretreated #Patients should receive a loading dose of prasugrel, provided that they were not pretreated with another P2Y12 receptor inhibitor. The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.290 with clopidogrel or ticagrelor, it is useful to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus ep- tifibatide, or high-dose bolus tirofiban) at the time of (Level of Evidence: A) Class IIa 1. In patients with NSTE-ACS and high-risk features (eg, elevated troponin) treated with UFH and ad- equately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofi- ban) at the time of PCI.195,383 (Level of Evidence: B) GP IIb/IIIa receptor antagonist therapy in patients with NSTE-ACS undergoing PCI reduced the incidence of com- posite ischemic events, primarily through a decrease in documented MI, although in some trials this is counter- balanced by an increased rate of bleeding.193,195,310,379 382,392 Most, but not all, randomized trials of the use of GP IIb/IIIa inhibitor were conducted in the era before clopidogrel Abciximab, double-bolus eptifiba- tide, and high-bolus dose tirofiban result in a high degree of platelet inhibition, reduce ischemic complications in patients undergoing PCI, and appear to afford comparable angio- graphic and clinical outcomes.26 As trials of the GP IIb/IIIa inhibitors generally excluded patients at high risk of bleed- ing, recommendations for the use of GP IIb/IIIa inhibitors are best understood as applying to patients not at high risk of bleeding complications.


In patients with NSTE-ACS and high-risk features (eg, elevated troponin) treated with UFH and ad- equately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofi- ban) at the time of PCI.195,383 (Level of Evidence: B) GP IIb/IIIa receptor antagonist therapy in patients with NSTE-ACS undergoing PCI reduced the incidence of com- posite ischemic events, primarily through a decrease in documented MI, although in some trials this is counter- balanced by an increased rate of bleeding.193,195,310,379 382,392 Most, but not all, randomized trials of the use of GP IIb/IIIa inhibitor were conducted in the era before clopidogrel Abciximab, double-bolus eptifiba- tide, and high-bolus dose tirofiban result in a high degree of platelet inhibition, reduce ischemic complications in patients undergoing PCI, and appear to afford comparable angio- graphic and clinical outcomes.26 As trials of the GP IIb/IIIa inhibitors generally excluded patients at high risk of bleed- ing, recommendations for the use of GP IIb/IIIa inhibitors are best understood as applying to patients not at high risk of bleeding complications. Although GP IIb/IIIa inhibitors were used in 27% and 55% of patients, respectively, in the PLATO (Platelet Inhibition and Patient Outcomes) and TRITON studies of ticagrelor and prasugrel, there are insufficient (and no RCT data) from which to make specific recommendations about GP IIb/IIIa inhibitor use in patients treated with either of these P2Y12 inhibitors. See Online Data Supplement 21 for additional information on GP IIb/IIIa inhibitors. 5.1.2.3. Anticoagulant Therapy in Patients Undergoing PCI: Recommendations Class I 1. An anticoagulant should be administered to patients with NSTE-ACS undergoing PCI to reduce the risk of intracoronary and catheter thrombus formation. (Level of Evidence: C) 2. Intravenous UFH is useful in patients with NSTE- ACS undergoing PCI. (Level of Evidence: C) 3.


Intravenous UFH is useful in patients with NSTE- ACS undergoing PCI. (Level of Evidence: C) 3. Bivalirudin is useful as an anticoagulant with or without prior treatment with UFH in patients with NSTE-ACS undergoing PCI.310,394 398 (Level of Evi- dence: B) 4. An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to pa- tients with NSTE-ACS who have received fewer than 2 therapeutic subcutaneous doses (eg, 1 mg/kg SC) or received the last subcutaneous enoxaparin (Level of Evi- dence: B) 5. If PCI is performed while the patient is on fondaparinux, an additional 85 IU/kg of UFH should be given intravenously immediately before PCI be- cause of the risk of catheter thrombosis (60 IU/kg IV if a GP IIb/IIIa inhibitor used with UFH dosing based on the target-activated clotting time).26,313 315,404 (Level of Evidence: B) 6. In patients with NSTE-ACS, anticoagulant therapy should be discontinued after PCI unless there is a compelling reason to continue such therapy. (Level of Evidence: C) Class IIa 1. In patients with NSTE-ACS undergoing PCI who are at high risk of bleeding, it is reasonable to use bivali- rudin monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist.310,396 (Level of Evidence: B) Class IIb 1. Performance of PCI with enoxaparin may be reason- able in patients treated with upstream subcutaneous enoxaparin for NSTE-ACS.26,309,399 402,405,406 (Level of Evidence: B) Class III: Harm 1.


Performance of PCI with enoxaparin may be reason- able in patients treated with upstream subcutaneous enoxaparin for NSTE-ACS.26,309,399 402,405,406 (Level of Evidence: B) Class III: Harm 1. Fondaparinux should not be used as the sole an- ticoagulant to support PCI in patients with NSTE- ACS due to an increased risk of catheter thrombo- (Level of Evidence: B) Anticoagulant therapy prevents thrombus formation at the site of arterial injury, on the coronary guide wire, and in the catheters used for PCI.26,407 With rare exceptions, all PCI studies have used some form of anticoagulant at the time Intravenous UFH and bivalirudin both have Class I recommendations in patients undergoing PCI in the 2011 Patients who have received multiple doses of subcutaneously-administered enoxaparin who undergo PCI within 8 hours of the last subcutaneous dose generally have received adequate anticoagulation to undergo PCI, but the degree of anticoagulation may diminish 8 to 12 hours after the last subcutaneous dose. In such patients, as well as in patients who have received fewer than 2 subcutaneous doses of enoxaparin, the addition of enoxaparin (0.3 mg/kg IV) at the time of PCI provides additional anticoagulation and has become standard practice.26,309,399 403 Patients who undergo PCI >12 hours after the last subcutaneous dose of enoxa- parin are usually treated with full-dose de novo anticoagu- lation with an established regimen (eg, full-dose UFH or bivalirudin). Fondaparinux as the sole anticoagulant during PCI has been associated with catheter thrombosis, and use of an anticoagulant with anti-IIa activity is recommended when patients treated with fondaparinux undergo PCI.313 315 One suggested regimen is UFH 85 IU/kg IV if no GP IIb/IIIa inhibitor is used and 60 IU/kg IV if a GP IIb/IIIa inhibitor is used with UFH dosing based on the target-activated clotting Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e375 5.2.


Fondaparinux as the sole anticoagulant during PCI has been associated with catheter thrombosis, and use of an anticoagulant with anti-IIa activity is recommended when patients treated with fondaparinux undergo PCI.313 315 One suggested regimen is UFH 85 IU/kg IV if no GP IIb/IIIa inhibitor is used and 60 IU/kg IV if a GP IIb/IIIa inhibitor is used with UFH dosing based on the target-activated clotting Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e375 5.2. Timing of Urgent CABG in Patients With NSTE-ACS in Relation to Use of Antiplatelet Agents: Recommendations Class I 1. Non enteric-coated aspirin (81 mg to 325 mg daily) should be administered preoperatively to patients (Level of Evidence: B) 2. In patients referred for elective CABG, clopidogrel and ticagrelor should be discontinued for at least (Level of Evidence: B) and prasugrel for at least 7 days before surgery.8,414 (Level of Evidence: C) 3. In patients referred for urgent CABG, clopidogrel and ticagrelor should be discontinued for at least 24 hours to reduce major bleeding.8,412,415 417 (Level of Evidence: B) 4. In patients referred for CABG, short-acting intrave- nous GP IIb/IIIa inhibitors (eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before and abciximab for at least 12 hours be- fore to limit blood loss and transfusion.389 (Level of Evidence: B) Class IIb 1. In patients referred for urgent CABG, it may be reasonable to perform surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has been discontin- ued.


In patients referred for urgent CABG, it may be reasonable to perform surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has been discontin- ued. (Level of Evidence: C) In-hospital CABG is performed in 7% to 13% of patients hospitalized with NSTE-ACS.420 422 Approximately one third of patients with NSTEMI undergo CABG within 48 hours of In these patients, CABG was performed at a median time of 73 hours after admission (interquartile In-hospital mortality in patients with NSTEMI undergoing CABG is approximately 3.7%.421 Recommendations for management of patients treated with oral and intravenous antiplatelet agents who undergo CABG are given in the 2011 CABG CPG.23 Preoperative aspirin reduces operative morbidity and mortality, and CABG can be performed safely in patients on aspirin therapy with only a modest increase in bleeding risk.23,408 410 The use of inhibitors in patients with NSTE-ACS is associated with an increase in post CABG bleeding and the need for Although it is recommended that clopidogrel and ticagrelor be discontinued at least 5 days before surgery and prasugrel at least 7 days before surgery in patients referred for elective CABG,23,411 413 the timing of CABG in patients with NSTE-ACS treated with a P2Y12 should reflect a balance of the potential increase in bleeding against the potential benefits of not delaying sur- gery 5 to 7 days.


(Level of Evidence: C) In-hospital CABG is performed in 7% to 13% of patients hospitalized with NSTE-ACS.420 422 Approximately one third of patients with NSTEMI undergo CABG within 48 hours of In these patients, CABG was performed at a median time of 73 hours after admission (interquartile In-hospital mortality in patients with NSTEMI undergoing CABG is approximately 3.7%.421 Recommendations for management of patients treated with oral and intravenous antiplatelet agents who undergo CABG are given in the 2011 CABG CPG.23 Preoperative aspirin reduces operative morbidity and mortality, and CABG can be performed safely in patients on aspirin therapy with only a modest increase in bleeding risk.23,408 410 The use of inhibitors in patients with NSTE-ACS is associated with an increase in post CABG bleeding and the need for Although it is recommended that clopidogrel and ticagrelor be discontinued at least 5 days before surgery and prasugrel at least 7 days before surgery in patients referred for elective CABG,23,411 413 the timing of CABG in patients with NSTE-ACS treated with a P2Y12 should reflect a balance of the potential increase in bleeding against the potential benefits of not delaying sur- gery 5 to 7 days. The risk of major bleeding complications is increased when CABG is performed <24 hours after dis- continuation of clopidogrel.23,416,417 In patients who undergo CABG 1 to 4 days after discontinuation of clopidogrel, it appears that the incidence of life-threatening bleeding is not significantly increased, but an increase in blood transfusions is In the TRITON-TIMI 38 trial,302 the inci- dence of CABG-related major bleeding was higher in patients treated with prasugrel than in patients treated with clopido- In the PLATO trial, the rates of major bleeding and transfusion requirements were similar between patients treated with ticagrelor and patients treated with clopidogrel.294 The more rapid recovery of platelet function in pharmacokinetic Table 9.


The risk of major bleeding complications is increased when CABG is performed <24 hours after dis- continuation of clopidogrel.23,416,417 In patients who undergo CABG 1 to 4 days after discontinuation of clopidogrel, it appears that the incidence of life-threatening bleeding is not significantly increased, but an increase in blood transfusions is In the TRITON-TIMI 38 trial,302 the inci- dence of CABG-related major bleeding was higher in patients treated with prasugrel than in patients treated with clopido- In the PLATO trial, the rates of major bleeding and transfusion requirements were similar between patients treated with ticagrelor and patients treated with clopidogrel.294 The more rapid recovery of platelet function in pharmacokinetic Table 9. Dosing of Parenteral Anticoagulants During PCI Drug* In Patients Who Have Received Prior Anticoagulant Therapy In Patients Who Have Not Received Prior Anticoagulant Therapy Enoxaparin For prior treatment with enoxaparin, if last SC dose was administered 8 12 h earlier or if <2 therapeutic SC doses of enoxaparin have been administered, an IV dose of enoxaparin 0.3 mg/kg should be given 0.5 mg/kg-0.75 mg/kg IV loading dose If the last SC dose was administered within prior 8 h, no additional enoxaparin should be given Bivalirudin For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV loading dose, then 1.75 mg/kg/h IV infusion 0.75 mg/kg loading dose, 1.75 mg/kg/h IV infusion For patients already receiving bivalirudin infusion, give additional loading dose 0.5 mg/kg and increase infusion to 1.75 mg/kg/h during PCI Fondaparinux For prior treatment with fondaparinux, administer additional IV treatment with anticoagulant possessing anti-IIa activity, considering whether GPI receptor antagonists have been administered N/A UFH IV GPI planned: additional UFH as needed (eg, 2000 5000 U) to achieve ACT of 200 250 s IV GPI planned: 50 70 U/kg loading dose to achieve ACT of No IV GPI planned: additional UFH as needed (eg, 2000 5000 U) to achieve ACT of 250 300 s for HemoTec, 300 350 s for Hemochron No IV GPI planned: 70 100 U/kg loading dose to achieve target ACT of 250 300 s for HemoTec, 300 350 s for Hemochron *Drugs presented in order of the COR and then the LOE as noted in the Preamble.


Dosing of Parenteral Anticoagulants During PCI Drug* In Patients Who Have Received Prior Anticoagulant Therapy In Patients Who Have Not Received Prior Anticoagulant Therapy Enoxaparin For prior treatment with enoxaparin, if last SC dose was administered 8 12 h earlier or if <2 therapeutic SC doses of enoxaparin have been administered, an IV dose of enoxaparin 0.3 mg/kg should be given 0.5 mg/kg-0.75 mg/kg IV loading dose If the last SC dose was administered within prior 8 h, no additional enoxaparin should be given Bivalirudin For patients who have received UFH, wait 30 min, then give 0.75 mg/kg IV loading dose, then 1.75 mg/kg/h IV infusion 0.75 mg/kg loading dose, 1.75 mg/kg/h IV infusion For patients already receiving bivalirudin infusion, give additional loading dose 0.5 mg/kg and increase infusion to 1.75 mg/kg/h during PCI Fondaparinux For prior treatment with fondaparinux, administer additional IV treatment with anticoagulant possessing anti-IIa activity, considering whether GPI receptor antagonists have been administered N/A UFH IV GPI planned: additional UFH as needed (eg, 2000 5000 U) to achieve ACT of 200 250 s IV GPI planned: 50 70 U/kg loading dose to achieve ACT of No IV GPI planned: additional UFH as needed (eg, 2000 5000 U) to achieve ACT of 250 300 s for HemoTec, 300 350 s for Hemochron No IV GPI planned: 70 100 U/kg loading dose to achieve target ACT of 250 300 s for HemoTec, 300 350 s for Hemochron *Drugs presented in order of the COR and then the LOE as noted in the Preamble. When more than 1 drug exists within the same LOE, and there are no comparative data, then the drugs are listed alphabetically.


When more than 1 drug exists within the same LOE, and there are no comparative data, then the drugs are listed alphabetically. ACT indicates activated clotting time; COR, Class of Recommendation; GPI, glycoprotein IIb/IIIa inhibitor; IV, intravenous; LOE, Level of Evidence; N/A, not applicable; PCI, percutaneous coronary intervention; SC, subcutaneous; and UFH, unfractionated heparin. Modified from Levine et al.26 studies of ticagrelor did not translate to a lower risk of bleed- ing or lessen the need for transfusion compared with clopido- grel when CABG was performed early (ie, <5 days) after drug See Online Data Supplements 21 and 22 for more informa- tion on myocardial revascularization. 6. Late Hospital Care, Hospital Discharge, And Posthospital Discharge Care 6.1. General Principles (Cardioprotective Therapy and Symptom Management) The goals of therapy after NSTE-ACS are to restore the patient to normal activities to the extent possible and to use the acute event to re-evaluate the plan of care, particularly lifestyle and risk factor modification. Aggressive risk factor modifications that can prolong survival should be the main goal of long-term management of patients with stable CAD. Patients presenting with NSTE-ACS represent a high-risk cohort in whom sec- ondary cardiovascular disease prevention is likely to be par- ticularly effective (Table 10). Clinicians have an opportunity to provide evidence-based care to this high-risk cohort and to aggressively treat the underlying atherosclerotic process through lifestyle modification and effective pharmacological In most cases, the inpatient anti-ischemic medi- cal regimen should be continued after discharge, and the anti- platelet/anticoagulant medications should be changed to an outpatient regimen.


Clinicians have an opportunity to provide evidence-based care to this high-risk cohort and to aggressively treat the underlying atherosclerotic process through lifestyle modification and effective pharmacological In most cases, the inpatient anti-ischemic medi- cal regimen should be continued after discharge, and the anti- platelet/anticoagulant medications should be changed to an outpatient regimen. The goals for continued medical therapy after discharge relate to potential prognostic benefits (primar- ily shown for antiplatelet agents, beta blockers, statins, and inhibitors of the renin-angiotensin aldosterone system, espe- cially for LVEF <0.40).Added benefits are control of ischemic symptoms (nitrates, beta blockers, CCBs, and ranolazine) and treatment of major risk factors such as smoking, hypertension, dyslipidemia, physical inactivity, obesity, and diabetes mel- Selection of a medical regimen should be individual- ized to each patient on the basis of in-hospital findings, risk factors for CAD, drug tolerability, and recent procedural inter- ventions. The mnemonic ABCDE (Aspirin, Antianginals, and ACE Inhibitors; Beta Blockers and BP; Cholesterol and Cigarettes; Diet and Diabetes Mellitus; Education and Exercise) is useful in guiding treatment.428 6.2. Medical Regimen and Use of Medications at Discharge: Recommendations Class I 1. Medications required in the hospital to control isch- emia should be continued after hospital discharge in patients with NSTE-ACS who do not undergo coro- nary revascularization, patients with incomplete or unsuccessful revascularization, and patients with re- current symptoms after revascularization. Titration of the doses may be required.427,428 (Level of Evidence: C) 2. All patients who are post NSTE-ACS should be giv- en sublingual or spray nitroglycerin with verbal and written instructions for its use.429 (Level of Evidence: C) 3.


All patients who are post NSTE-ACS should be giv- en sublingual or spray nitroglycerin with verbal and written instructions for its use.429 (Level of Evidence: C) 3. Before hospital discharge, patients with NSTE-ACS should be informed about symptoms of worsening myocardial ischemia and MI and should be given verbal and written instructions about how and when to seek emergency care for such symptoms.429 (Level of Evidence: C) 4. Before hospital discharge, patients who are post NSTE-ACS and/or designated responsible caregiv- ers should be provided with easily understood and culturally sensitive verbal and written instructions about medication type, purpose, dose, frequency, side effects, and duration of use.429 (Level of Evidence: C) 5. For patients who are post NSTE-ACS and have ini- tial angina lasting more than 1 minute, nitroglycerin (1 dose sublingual or spray) is recommended if an- gina does not subside within 3 to 5 minutes; call 9-1-1 immediately to access emergency medical services.429 (Level of Evidence: C) 6. If the pattern or severity of angina changes, suggest- ing worsening myocardial ischemia (eg, pain is more frequent or severe or is precipitated by less effort or occurs at rest), patients should contact their clinician without delay to assess the need for additional treat- ment or testing.429 (Level of Evidence: C) 7. Before discharge, patients should be educated about modification of cardiovascular risk factors.428 (Level of Evidence: C) 6.2.1. Late Hospital and Posthospital Oral Antiplatelet Therapy: Recommendations Class I 1. Aspirin should be continued indefinitely. The mainte- nance dose should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all other (Level of Evidence: A) 2.


The mainte- nance dose should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all other (Level of Evidence: A) 2. In addition to aspirin, a P2Y12 inhibitor (either clopi- dogrel or ticagrelor) should be continued for up to 12 months in all patients with NSTE-ACS without contraindications who are treated with an ischemia- guided strategy. Options include: Clopidogrel: 75 mg daily289,296 (Level of Evidence: B) or Ticagrelor : 90 mg twice daily293,294 (Level of Evidence: B) 3. In patients receiving a stent (bare-metal stent or DES) during PCI for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months.330 Options include: Clopidogrel: 75 mg daily296,331 (Level of Evidence: B) or Prasugrel#: 10 mg daily302 (Level of Evidence: B) or Ticagrelor : 90 mg twice daily293 (Level of Evi dence: B) Class IIa 1. It is reasonable to use an aspirin maintenance dose of 81 mg per day in preference to higher maintenance The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.290 #Patients should receive a loading dose of prasugrel, provided they were not pretreated with another P2Y12 receptor inhibitor. Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e377 Table 10.


Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e377 Table 10. Plan of Care for Patients With NSTE-ACS Plan of Care Resources/References Medications Antithrombotic therapies Sections 6.2.1 and 6.2.2 Beta blockers Section 4.1.2.3 ACE inhibitors/ARBs/aldosterone antagonists Section 4.2 CCBs Section 4.1.2.4 Statins 2013 Blood cholesterol CPG18 Discontinuation of antithrombotic therapies for elective surgical and medical procedures with increased risk of bleeding 2014 SIHD focused update10 2012 Management of AMI in patients with persistent STEMI CPG19 2011 Secondary prevention CPG27 2007 Science Advisory on the prevention of premature discontinuation of DAPT in patients with coronary artery stents504 Inappropriate use of analgesics (NSAIDs) 2010 Expert consensus document on PPIs and thienopyridines430 Use of PPIs 2011 PCI CPG26 Risk factor modification/lifestyle interventions and physical activity/cardiac rehabilitation Smoking cessation Tobacco cessation toolkit505 Diet nutrition 2013 Lifestyle CPG15 Physical activity 2013 Lifestyle CPG15 2011 Secondary prevention CPG27 Cardiorespiratory fitness (MET capacity) 2011 Secondary prevention CPG27 2010 Performance measures on cardiac rehabilitation454 2012 Scientific statement on sexual activity and cardiovascular disease231 Management of comorbidities Overweight/obesity 2013 Obesity CPG16 2011 Secondary prevention CPG27 Statins 2013 Lifestyle CPG15 2013 Blood cholesterol CPG18 Hypertension 2014 Report on high BP501 2013 Science advisory on high BP control506 Diabetes mellitus 2013 Position statement on standards of medical care in diabetes507 HF 2013 HF CPG14 Arrhythmia/Arrhythmia risk 2012 Focused update incorporated into the 2008 DBT CPG20 Psychosocial factors Sexual activity 2012 Scientific statement on sexual activity and cardiovascular disease231 2013 Consensus document on sexual counseling for individuals with cardiovascular disease and their partners508 Gender-Specific issues 2007 Cardiovascular disease prevention in women CPG475 Depression, stress, and anxiety 2008 Science advisory on depression and coronary heart disease509 Alcohol use 2011 Secondary prevention CPG27 Culturally sensitive issues 2009 Consensus report on a comprehensive framework and preferred practices for measuring and reporting cultural competency510 Return to work schedule Clinician follow-up Cardiologist 2011 Secondary prevention CPG27 2013 Hospital to Home Quality Initiative511 Primary care clinician Advanced practice nurse/physician assistant Pharmacists 2013 Discharge counseling for patients with HF or MI512 Other relevant medical specialists Electronic personal health records Influenza vaccination 2005 Recommendations for prevention and control of influenza37 (Continued) doses in patients with NSTE-ACS treated either inva- sively or with coronary stent implantation.26,331,368,385 388 (Level of Evidence: B) 2.


It is reasonable to use ticagrelor in preference to clop- idogrel for maintenance P2Y12 treatment in patients with NSTE-ACS who undergo an early invasive or (Level of Evidence: B) 3. It is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 treatment in patients with NSTE-ACS who undergo PCI who are not at high risk for bleeding complications.302,303 (Level of Evidence: B) 4. If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of inhibitor therapy after stent implantation, ear- lier discontinuation (eg, <12 months) of P2Y12 inhibi- tor therapy is reasonable.330 (Level of Evidence: C) Class IIb 1. Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implanta- tion. (Level of Evidence: C) 6.2.2. Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTE-ACS Class I 1. The duration of triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 recep- tor inhibitor in patients with NSTE-ACS should be minimized to the extent possible to limit the risk of bleeding. (Level of Evidence: C) 2. Proton pump inhibitors should be prescribed in pa- tients with NSTE-ACS with a history of gastroin- testinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a (Level of Evidence: C) Class IIa 1. Proton pump inhibitor use is reasonable in patients with NSTE-ACS without a known history of gastro- intestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a (Level of Evidence: C) Class IIb 1. Targeting oral anticoagulant therapy to a lower in- ternational normalized ratio (INR) (eg, 2.0 to 2.5) may be reasonable in patients with NSTE-ACS man- aged with aspirin and a P2Y12 inhibitor.


Targeting oral anticoagulant therapy to a lower in- ternational normalized ratio (INR) (eg, 2.0 to 2.5) may be reasonable in patients with NSTE-ACS man- aged with aspirin and a P2Y12 inhibitor. (Level of Evidence: C) The combination of oral antiplatelet therapy and oral anti- coagulant therapy significantly increases the risk of bleed- ing. This risk varies widely, but on average, the addition of a single antiplatelet agent increased the risk of bleeding from a range of 2% to 3% to a range of 4% to 6%, whereas the addi- tion of DAPT to oral anticoagulant therapy ( triple therapy ) increased the risk of bleeding from a range of 4% to 6% to a range of 10% to 14%.432 435 This risk was also related to the duration of triple therapy. In patients with NSTE-ACS in whom there are indica- tions for triple therapy, the benefit of such therapy in terms of prevention of stent thrombosis, thromboembolic events, and recurrent MI must be weighed against the risk of bleeding complications.


In patients with NSTE-ACS in whom there are indica- tions for triple therapy, the benefit of such therapy in terms of prevention of stent thrombosis, thromboembolic events, and recurrent MI must be weighed against the risk of bleeding complications. Similarly, DAPT, in addition to anticoagulant Patient/family education Plan of care for AMI 2010 CPG for cardiopulmonary resuscitation and emergency cardiovascular care part 9: postcardiac arrest care31 Recognizing symptoms of MI Activating EMS, signs and symptoms for urgent vs. emergency evaluations CPR training for family members Risk assessment and prognosis Advanced directives Social networks/social isolation Socioeconomic factors Access to health insurance coverage Access to clinicians Effective communication and care coordination513 Disability Cardiovascular disability: updating Social Security listings514 Social services Community services ACE indicates angiotensin-converting enzyme; AF, atrial fibrillation; AMI, acute myocardial infarction; ARB, angiotensin receptor blocker; BP, blood pressure; CCB, calcium channel blocker; CPG, clinical practice guideline; CPR, cardiopulmonary resuscitation; DAPT, dual antiplatelet therapy; DBT, device-based therapy; ECC, emergency cardiovascular care; EMS, emergency medical services; HF, heart failure; MET, metabolic equivalent; MI, myocardial infarction; NSAID, nonsteroidal anti-inflammatory drug; NSTE-ACS, non T-elevation acute coronary syndromes; PCI, percutaneous coronary intervention; PPI, protein pump inhibitor; SIHD, stable ischemic heart disease; and STEMI, ST-elevation myocardial infarction. Table 10. Continued Plan of Care Resources/References Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e379 therapy, requires consideration of the increased risk of bleed- ing. It is essential that therapeutic decision making in this crit- ical area include discussion with the patient about the options, advantages, and limitations of available approaches.


It is essential that therapeutic decision making in this crit- ical area include discussion with the patient about the options, advantages, and limitations of available approaches. Recommendations about the management of patients treated with triple therapy have been published in ACC/AHA CPGs and by other organizations.17,26,430,433,436 Although some organi- zations have recommended a target INR of 2.0 to 2.5 in patients with atrial fibrillation (AF) who require triple therapy,437 others continue to recommend a target INR of 2.0 to 3.0.12,436 The HAS- BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/ Alcohol Concomitantly) score has relevance in these delibera- No prospective study to date has demonstrated that a target INR of 2.0 to 2.5 reduces bleeding complications. Whenever possible, shorter durations of triple therapy are favored in preference to longer durations of triple therapy. In patients with NSTE-ACS who require oral anticoagulation for AF, mechanical heart valve, deep venous thrombosis, or other conditions, a bare-metal stent may offer the advantages of lower bleeding risk over a DES because of the potentially shorter dura- tion of triple antithrombotic therapy. The WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary Stenting) trial is the first published study to address the question of optimal antiplate- let therapy in patients taking oral anticoagulant medication.440 WOEST was a randomized, open-label trial of 563 patients (approximately 25% of whom had NSTE-ACS) receiving oral anticoagulant therapy and undergoing coronary stenting. Patients randomized to single antiplatelet treatment with clopidogrel had significantly fewer bleeding complications and no increase in thrombotic events compared with those randomized to DAPT with aspirin and clopidogrel. Larger clinical trials are needed to compare double versus triple therapy in the setting of coronary stenting and NSTE-ACS.


Larger clinical trials are needed to compare double versus triple therapy in the setting of coronary stenting and NSTE-ACS. One such study that has been initiated is PIONEERAF-PCI (an Open-Label, Randomized, Controlled, Multicenter Study Exploring two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation who Undergo Percutaneous Coronary Intervention). Although there are some data on therapy with aspirin, clop- idogrel, and warfarin, there is sparse information on the use of inhibitors (prasugrel, ticagrelor), direct thrombin inhibitor (dabigatran), or factor-Xa inhibitors (rivaroxaban, apixaban) in patients receiving triple therapy. Prasugrel302 produce a greater degree of platelet inhibi- tion than clopidogrel and are associated with greater rates of These are important potential disadvan- tages in patients requiring triple therapy, a group in which the inherent risks of bleeding are significantly increased. (Overall bleeding risk was not increased with ticagrelor, although there was increased bleeding in certain subgroups on this drug).412 Because there are no well-established therapies to reverse the anticoagulant effects of the newer oral antiplatelet agents, caution is required when considering the use of these agents in patients who require triple therapy and are at significantly increased risk of bleeding. This admonition is especially important in elderly patients, a group in which bleeding risk is inherently increased (Section 7.1). Proton pump inhibitors decrease the risk of gastrointesti- nal bleeding in patients treated with DAPT431 and are used in patients treated with DAPT who have a history of gastrointes- tinal bleeding and those at increased risk of bleeding, which is associated with oral anticoagulation therapy even if there is no history of gastrointestinal bleeding.430 On the basis of these results, proton pump inhibitors are also used in patients receiving triple antithrombotic therapy who have a history of gastrointestinal bleeding.


Proton pump inhibitors decrease the risk of gastrointesti- nal bleeding in patients treated with DAPT431 and are used in patients treated with DAPT who have a history of gastrointes- tinal bleeding and those at increased risk of bleeding, which is associated with oral anticoagulation therapy even if there is no history of gastrointestinal bleeding.430 On the basis of these results, proton pump inhibitors are also used in patients receiving triple antithrombotic therapy who have a history of gastrointestinal bleeding. Although the clinical evidence that omeprazole and esomeprazole diminish the antiplate- let efficacy of clopidogrel is weak,430 the US Food and Drug Administration has issued a warning to avoid concomitant use of these 2 proton pump inhibitors with clopidogrel.442 6.2.3. Platelet Function and Genetic Phenotype Testing Although higher platelet reactivity has been associated with a greater incidence of adverse events in patients undergoing stent implantation, a strategy of adjusting antiplatelet therapy based on routine platelet function testing has not been ben- eficial in reducing ischemic complications.26,443 445 Similarly, a strategy of routine genetic phenotype testing has also not been beneficial and thus is not recommended.26,446 448 A more detailed discussion of these issues and current recommenda- tions about platelet function testing and genetic testing are in 6.3. Risk Reduction Strategies for Secondary Prevention Secondary prevention is a critical aspect of the management of care for the survivor of NSTE-ACS. It has been clearly estab- lished that in this high-risk cohort, subsequent cardiovascular morbidity and mortality can be reduced by a comprehensive approach to favorably modifying patients risk profiles.27 Secondary prevention comprises lifestyle changes, risk fac- tor education, medical therapy, and, where appropriate, revas- cularization. These elements are discussed in Section 6.4.


It has been clearly estab- lished that in this high-risk cohort, subsequent cardiovascular morbidity and mortality can be reduced by a comprehensive approach to favorably modifying patients risk profiles.27 Secondary prevention comprises lifestyle changes, risk fac- tor education, medical therapy, and, where appropriate, revas- cularization. These elements are discussed in Section 6.4. Despite the proven utility of secondary prevention, its imple- mentation remains suboptimal, and enhanced application is a major goal in this patient population. See Online Data Supplement 23 for additional information on risk reduction strategies. 6.3.1. Cardiac Rehabilitation and Physical Activity: Recommendation Class I 1. All eligible patients with NSTE-ACS should be re- ferred to a comprehensive cardiovascular rehabilita- tion program either before hospital discharge or dur- ing the first outpatient visit.449 452 (Level of Evidence: B) The US Public Health Service emphasizes comprehensive car- diac rehabilitation programs,449 and the 2011 secondary pre- vention CPG underscores referral to cardiac rehabilitation for survivors of ACS.27 Since 2007, referral to these programs has been designated a quality performance measure.453 455 Barriers to referral can be obviated by discussion with the patient and referral by the patient s primary care clinician and/or cardio- vascular caregiver. These comprehensive programs provide patient education, enhance regular exercise, monitor risk factors, and address lifestyle modification.456 Aerobic exercise training can generally begin 1 to 2 weeks after discharge in patients treated with PCI or CABG.457 Mild-to-moderate resis- tance training can be considered and started 2 to 4 weeks after Unsupervised exercise may target a heart rate range of 60% to 75% of maximum age-predicted heart rate based on the patient s exercise stress test. Supervised training may target a higher heart rate (70% to 85% of age-predicted Additional restrictions apply when residual isch- emia is present.


Supervised training may target a higher heart rate (70% to 85% of age-predicted Additional restrictions apply when residual isch- emia is present. Daily walking can be encouraged soon after discharge for most patients. Resource publications on exer- cise prescription in cardiovascular patients are available.456,457 Regular physical activity reduces symptoms in patients with cardiovascular disease, enhances functional capacity, improves other risk factors such as insulin resistance and glucose con- trol, and is important in weight control.456 Questionnaires and nomograms for cardiac patients have been developed to guide exercise prescription if an exercise test is unavailable.459 462 See Section 6.4 and Table 10 for more information. 6.3.2. Patient Education: Recommendations Class I 1. Patients should be educated about appropriate cho- lesterol management, BP, smoking cessation, and life- (Level of Evidence: C) 2. Patients who have undergone PCI or CABG derive benefit from risk factor modification and should receive counseling that revascularization does not obviate the need for lifestyle changes.463 (Level of Evidence: C) Results of testing should be discussed with the patient, the patient s family, and/or the patient s advocate in an under- standable manner. Test results should be used to help deter- mine the advisability of coronary angiography, the need for adjustments in the medical regimen, and the specifics for sec- ondary prevention measures. See Section 6.4 and Table 10 for more information on plan of care. 6.3.3. Pneumococcal Pneumonia: Recommendation Class I 1. The pneumococcal vaccine is recommended for patients 65 years of age and older and in high-risk patients with cardiovascular disease.464 466 (Level of Evidence: B) Vaccination with the 23-valent pneumococcal polysaccha- ride vaccine is recommended for all adults 65 years of age. Adults of any age who are at increased risk, including smok- ers and those with asthma, should also be given the vaccine.


Adults of any age who are at increased risk, including smok- ers and those with asthma, should also be given the vaccine. Immunocompromised adults should receive the 13-valent conjugate vaccine in addition to the 23-valent vaccine.464 466 The influenza vaccine is discussed in Section 6.4. 6.3.4. NSAIDs: Recommendations Class I 1. Before hospital discharge, the patient s need for treat- ment of chronic musculoskeletal discomfort should be assessed, and a stepped-care approach should be used for selection of treatments. Pain treatment be- fore consideration of NSAIDs should begin with ac- etaminophen, nonacetylated salicylates, tramadol, or small doses of narcotics if these medications are not (Level of Evidence: C) Class IIa 1. It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, nonacetylated salicylates, tramadol, or small doses of narcotics is insufficient.237 (Level of Evidence: C) Class IIb 1. NSAIDs with increasing degrees of relative COX- 2 selectivity may be considered for pain relief only for situations in which intolerable discomfort per- sists despite attempts at stepped-care therapy with acetaminophen, nonacetylated salicylates, tramadol, small doses of narcotics, or nonselective NSAIDs. In all cases, use of the lowest effective doses for the shortest possible time is encouraged.234,235,237,467 (Level of Evidence: C) Class III: Harm 1. NSAIDs with increasing degrees of relative COX- 2 selectivity should not be administered to patients with NSTE-ACS and chronic musculoskeletal dis- comfort when therapy with acetaminophen, nonac- etylated salicylates, tramadol, small doses of narcot- ics, or nonselective NSAIDs provide acceptable pain (Level of Evidence: B) Selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk, and the risk appears to be amplified in patients with established.


NSAIDs with increasing degrees of relative COX- 2 selectivity should not be administered to patients with NSTE-ACS and chronic musculoskeletal dis- comfort when therapy with acetaminophen, nonac- etylated salicylates, tramadol, small doses of narcot- ics, or nonselective NSAIDs provide acceptable pain (Level of Evidence: B) Selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk, and the risk appears to be amplified in patients with established. In a large Danish observa- tional study of patients with first MI (n=58432), the HR and There were dose-related increases in risk of death and non dose-dependent trends for rehospitaliza- tion for MI for all drugs.234,467 An AHA scientific statement on the use of NSAIDs concluded that the risk of cardiovascular events is proportional to COX-2 selectivity and the underly- ing risk in the patient.237 Non-pharmacological approaches were recommended as the first line of treatment, followed by the stepped-care approach to pharmacological therapy, as shown in Figure 4. 6.3.5. Hormone Therapy: Recommendation Class III: Harm 1. Hormone therapy with estrogen plus progestin, or estrogen alone, should not be given as new drugs for secondary prevention of coronary events to post- menopausal women after NSTE-ACS and should Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e381 not be continued in previous users unless the ben- efits outweigh the estimated risks.17,470 472 (Level of Evidence: A) Although prior observational data suggested a protective effect of hormone therapy for coronary events, a randomized trial of hormone therapy for secondary prevention of death and MI (the HERS [Heart and Estrogen/Progestin Replacement] study) failed to demonstrate a beneficial effect.473 There was an excess risk for death and MI early after initiation of hor- mone therapy.


Hormone therapy with estrogen plus progestin, or estrogen alone, should not be given as new drugs for secondary prevention of coronary events to post- menopausal women after NSTE-ACS and should Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e381 not be continued in previous users unless the ben- efits outweigh the estimated risks.17,470 472 (Level of Evidence: A) Although prior observational data suggested a protective effect of hormone therapy for coronary events, a randomized trial of hormone therapy for secondary prevention of death and MI (the HERS [Heart and Estrogen/Progestin Replacement] study) failed to demonstrate a beneficial effect.473 There was an excess risk for death and MI early after initiation of hor- mone therapy. The Women s Health Initiative included random- ized primary prevention trials of estrogen plus progestin and Both trials were stopped early owing to an increased risk related to hormone therapy that was believed to outweigh the potential benefits of further study.470 472 It is rec- ommended that post-menopausal women receiving hormone therapy at the time of a cardiovascular event discontinue its use and that hormone therapy should not be initiated for the primary or secondary prevention of coronary events. However, there may be other permissible indications for hormone therapy in postmenopausal women (eg, treatment of perimenopausal symptoms such as flushing or prevention of osteoporosis) if the benefits are believed to outweigh the increased cardiovascular risk. Postmenopausal women who are >1 to 2 years past the ini- tiation of hormone therapy who wish to continue such therapy for another compelling indication should weigh the risks and benefits, recognizing the greater risk of cardiovascular events and breast cancer (combination therapy) or stroke (estrogen).473 6.3.6. Antioxidant Vitamins and Folic Acid: Recommendations Class III: No Benefit 1.


Antioxidant Vitamins and Folic Acid: Recommendations Class III: No Benefit 1. Antioxidant vitamin supplements (eg, vitamins E, C, or beta carotene) should not be used for secondary prevention in patients with NSTE-ACS.474,475 (Level of Evidence: A) 2. Folic acid, with or without vitamins B6 and B12, should not be used for secondary prevention in pa- tients with NSTE-ACS.476,477 (Level of Evidence: A) Although there is an association of elevated homocysteine blood levels and CAD, a reduction in homocysteine levels with routine folate supplementation did not reduce the risk of CAD events in 2 trials (the NORVIT [Norwegian Vitamin Trial] and the HOPE [Heart Outcomes Prevention Evaluation] study) that included post MI or high-risk stable patients476 478 and produced poorer outcomes in another study.479 Additionally, in the NORVIT trial, there was a trend toward increased cardio- vascular events (95% CI: 1.00 to 1.50; P=0.05) in the cohort receiving the combination of folic acid, vitamin B6, and vita- min B12; the authors cautioned against using the treatment for Similarly, experience in large clinical trials with antioxidant vitamins has failed to demonstrate ben- efit for primary or secondary prevention.474,475,480 See Online Data Supplement 23 for additional information on antioxidant vitamins and folic acid. 6.4. Plan of Care for Patients With NSTE-ACS: Recommendations Class I 1. Posthospital systems of care designed to prevent hospital readmissions should be used to facilitate the transition to effective, coordinated outpatient care for all patients with NSTE-ACS.481 485 (Level of Evidence: B) 2. An evidence-based plan of care (eg, GDMT) that pro- motes medication adherence, timely follow-up with the healthcare team, appropriate dietary and physi- cal activities, and compliance with interventions for secondary prevention should be provided to patients with NSTE-ACS. (Level of Evidence: C) 3.


An evidence-based plan of care (eg, GDMT) that pro- motes medication adherence, timely follow-up with the healthcare team, appropriate dietary and physi- cal activities, and compliance with interventions for secondary prevention should be provided to patients with NSTE-ACS. (Level of Evidence: C) 3. In addition to detailed instructions for daily exer- cise, patients should be given specific instruction on activities (eg, lifting, climbing stairs, yard work, and household activities) that are permissible and those to avoid. Specific mention should be made of resump- tion of driving, return to work, and sexual activ- (Level of Evidence: B) 4. An annual influenza vaccination is recommended for patients with cardiovascular disease.27,488 (Level of Evidence: C) Education of patients with NSTEMI and their families is criti- cal and often challenging, especially during transitions of care. Failure to understand and comply with a plan of care may account for the high rate of AMI rehospitalization rates in the United States.489,490 An important intervention to promote Figure 4. Stepped-Care Approach to Pharmacological Therapy for Musculoskeletal Symptoms in Patients With Known Cardiovascular Disease or Risk Factors for Ischemic Heart Disease. ASA indicates aspirin; COX-2, cyclooxygenase; GI, gastrointestinal; NSAIDs, nonsteroidal anti-inflammatory drugs; and PPI, proton-pump inhibitor. Modified from Jneid et al.8 coordination is to provide patients and caregivers with a com- prehensive plan of care and educational materials during the hospital stay that support compliance with evidence-based thera- The posthospitalization plan of care for patients with NSTE-ACS (Table 10) should address in detail several complex issues, including medication adherence and titration, timely follow-up, dietary interventions, physical and sexual activities, cardiac rehabilitation, compliance with interventions for second- ary prevention, and reassessment of arrhythmic and HF risks.


Modified from Jneid et al.8 coordination is to provide patients and caregivers with a com- prehensive plan of care and educational materials during the hospital stay that support compliance with evidence-based thera- The posthospitalization plan of care for patients with NSTE-ACS (Table 10) should address in detail several complex issues, including medication adherence and titration, timely follow-up, dietary interventions, physical and sexual activities, cardiac rehabilitation, compliance with interventions for second- ary prevention, and reassessment of arrhythmic and HF risks. In addition, clinicians should pay close attention to psychoso- cial and socioeconomic issues, including access to care, risk of depression, social isolation, and healthcare disparities.494 496 6.4.1. Systems to Promote Care Coordination There has been improved understanding of the system changes necessary to achieve safer care.497 This includes adoption by all US hospitals of a standardized set of Safe Practices endorsed by the National Quality Forum,498 which over- lap with the National Patient Safety Goals espoused by The Examples of patient safety standards for all patients after AMI include improved communication among clinicians, nurses, and pharmacists; medication recon- ciliation; careful transitions between care settings; and con- sistent documentation. The National Quality Forum has also endorsed a set of patient-centered Preferred Practices for which detail comprehensive specifica- tions that are necessary to achieve successful care coordina- tion for patients and their families. Systems of care designed to support patients with NSTE-ACS, STEMI, and other car- diac diseases can result in significant improvement in patient outcomes. Table 10 provides reference documents for multiple risk-reduction strategies for secondary prevention in the post- hospital phase of NSTE-ACS. These include the 2013 ACC/ AHA CPGs on management of blood cholesterol,18 and the 2014 recommendations for management which were published during the develop- ment of this CPG.


These include the 2013 ACC/ AHA CPGs on management of blood cholesterol,18 and the 2014 recommendations for management which were published during the develop- ment of this CPG. To provide the interventions and services listed in Table 10, appropriate resources must be used so that patients with MI have full access to evidence-based therapies and follow-up care. There is a growing emphasis on penalizing hospitals for avoidable hospital readmissions. It is imperative for health systems to work with clinicians, nurses, pharmacists, communities, payers, and public agencies to support the inter- ventions that achieve comprehensive care. Several patient char- acteristics have been predictors of readmission after AMI.502,503 7. Special Patient Groups See Table 11 for summary of recommendations for this section. 7.1. NSTE-ACS in Older Patients: Recommendations Class I 1. Older patients** with NSTE-ACS should be treated with GDMT, an early invasive strategy, and revascu- larization as appropriate.515 519 (Level of Evidence: A) 2. Pharmacotherapy in older patients** with NSTE- ACS should be individualized and dose adjusted by weight and/or CrCl to reduce adverse events caused by age-related changes in pharmacokinetics/dynam- ics, volume of distribution, comorbidities, drug inter- actions, and increased drug sensitivity.515,520 522 (Level of Evidence: A) 3. Management decisions for older patients** with NSTE-ACS should be patient centered, and consider patient preferences/goals, comorbidities, functional (Level of Evidence: B) Class IIa 1. Bivalirudin, rather than a GP IIb/IIIa inhibitor plus UFH, is reasonable in older patients** with NSTE- ACS, both initially and at PCI, given similar efficacy but less bleeding risk.396,526 528 (Level of Evidence: B) 2.


Bivalirudin, rather than a GP IIb/IIIa inhibitor plus UFH, is reasonable in older patients** with NSTE- ACS, both initially and at PCI, given similar efficacy but less bleeding risk.396,526 528 (Level of Evidence: B) 2. It is reasonable to choose CABG over PCI in older patients** with NSTE-ACS who are appropriate can- didates, particularly those with diabetes mellitus or complex 3-vessel CAD (eg, SYNTAX score >22), with or without involvement of the proximal LAD artery, to reduce cardiovascular disease events and readmission and to improve survival.529 534 (Level of Evidence: B) In this CPG, older adults refers to patients 75 years of age.515 Older adults have the highest incidence, prevalence, and adverse outcomes of NSTE-ACS.9,515 517,535,536 Older age is accompanied by comorbidities, polypharmacy, and age- and disease-related physiological changes that adversely impact NSTE-ACS presen- tation, management, and outcome. As older patients are under- represented in clinical trials, the recommendations in this CPG are largely supported by registry data and meta-analyses.516,537 Older patients with NSTE-ACS primarily present with chest pain but frequently have atypical symptoms.


As older patients are under- represented in clinical trials, the recommendations in this CPG are largely supported by registry data and meta-analyses.516,537 Older patients with NSTE-ACS primarily present with chest pain but frequently have atypical symptoms. ECGs may be less diagnostic than in younger patients.517,538 Older patients with NSTE-ACS derive the same or greater benefit from phar- macological therapies, interventional therapies, and cardiac rehabilitation as younger patients, but older patients receive significantly less GDMT than younger patients, even when adjusted for comorbidities.515 517,535,538,539 In the ACSIS (Acute Coronary Syndrome Israeli Survey) registry, patients >80 years of age referred for early coronary angiography, compared with no angiography, had lower 30-day and 1-year mortality rates.540 Age-related pharmacokinetics and pharmacodynamic changes can alter drug dosing, efficacy, and safety of many NSTE-ACS therapies, as can drug drug interactions CrCl or glomerular filtra- tion rate (GFR) should be estimated initially and throughout care for all older patients with NSTE-ACS, and pharmaceuti- cal agents should be renally and weight dose-adjusted to limit drug toxicity (especially bleeding risk), given the unreliabil- ity of serum creatinine to assess age-related renal dysfunc- (Appendix 4, Table C). Bleeding in older patients with NSTE-ACS is multifactorial, resulting in nar- rower therapeutic windows.541,542,544,546,547 In the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With **Those 75 years of age (see text). Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e383 Early Implementation of the American College of Cardiology/ American Heart Association Guidelines) study, excessive doses of UFH, LMWH, and GP IIb/IIIa inhibitors accounted Aspirin should be maintained at 81 mg per day (after initial stent implantation).


Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e383 Early Implementation of the American College of Cardiology/ American Heart Association Guidelines) study, excessive doses of UFH, LMWH, and GP IIb/IIIa inhibitors accounted Aspirin should be maintained at 81 mg per day (after initial stent implantation). Owing to excess bleeding without clinical benefit, the US Food and DrugAdministration lists a Black Box warning that does not recommend adminis- tration of prasugrel to patients with NSTE-ACS who are 75 years of age or weigh <60 kg except in those at very high risk. A metaanalysis of 6 RCTs about the use of GP IIb/IIIa inhibitors in patients with NSTE-ACS reported no significant age-treatment interaction, although older women had signifi- cantly more adverse events.549 Bivalirudin appears safer for older patients with NSTE-ACS PCI than GP IIb/IIIa inhibi- tors plus UFH, with less bleeding and similar efficacy.526,550 AF is more common in older patients with NSTE-ACS, and triple therapy (DAPT and warfarin) entails a marked bleeding In the WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary Stenting) study, it was found that in patients taking oral coagulants who required PCI, use of clopidogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in thrombotic Nonetheless, practice should not be changed on the basis of this limited study alone.


A metaanalysis of 6 RCTs about the use of GP IIb/IIIa inhibitors in patients with NSTE-ACS reported no significant age-treatment interaction, although older women had signifi- cantly more adverse events.549 Bivalirudin appears safer for older patients with NSTE-ACS PCI than GP IIb/IIIa inhibi- tors plus UFH, with less bleeding and similar efficacy.526,550 AF is more common in older patients with NSTE-ACS, and triple therapy (DAPT and warfarin) entails a marked bleeding In the WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary Stenting) study, it was found that in patients taking oral coagulants who required PCI, use of clopidogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in thrombotic Nonetheless, practice should not be changed on the basis of this limited study alone. Older patients with NSTE-ACS benefit as much or more than younger patients from an early invasive strategy com- pared with an ischemia-guided strategy.340,341,515,518,519 In a 5-year follow-up meta-analysis of FRISC-II and RITA-3, an early invasive strategy versus an ischemia-guided strategy was associated with a significant reduction in death/MI and MI in patients 75 years of age but not in patients <65 years Although the highest risk reduction in death/MI with an early invasive strategy occurred in those 75 years of age, this strategy was associated with a 3-fold bleeding risk.552 However, despite the overall favorable evidence for an early invasive strategy in older patients, age is the strongest risk fac- tor for this group not undergoing an early invasive strategy.553 PCI has increased in older patients, including the very elderly ( 90 years of age), with success rates similar to younger patients and declining complication rates, including Several large registries report a greater RR reduction in mortality of older patients treated with revascularization versus medical therapy compared with those 65 years of age, despite increased comorbidities.517,540,554 556 Operative mortality rates for CABG in patients 80 years of age with NSTE-ACS range from 5% to 8% (11% for urgent cases) and increase to approximately 13% at 90 years of age.


Older patients with NSTE-ACS benefit as much or more than younger patients from an early invasive strategy com- pared with an ischemia-guided strategy.340,341,515,518,519 In a 5-year follow-up meta-analysis of FRISC-II and RITA-3, an early invasive strategy versus an ischemia-guided strategy was associated with a significant reduction in death/MI and MI in patients 75 years of age but not in patients <65 years Although the highest risk reduction in death/MI with an early invasive strategy occurred in those 75 years of age, this strategy was associated with a 3-fold bleeding risk.552 However, despite the overall favorable evidence for an early invasive strategy in older patients, age is the strongest risk fac- tor for this group not undergoing an early invasive strategy.553 PCI has increased in older patients, including the very elderly ( 90 years of age), with success rates similar to younger patients and declining complication rates, including Several large registries report a greater RR reduction in mortality of older patients treated with revascularization versus medical therapy compared with those 65 years of age, despite increased comorbidities.517,540,554 556 Operative mortality rates for CABG in patients 80 years of age with NSTE-ACS range from 5% to 8% (11% for urgent cases) and increase to approximately 13% at 90 years of age. Complications occur more frequently in older patients with Length of stay averages 6 days longer in older patients than in patients <50 years of age, and discharge (to home [52%]) is less frequent than in younger patients.557 In a metaanalysis, off-pump CABG appeared to offer a poten- tially safer and more effective revascularization technique compared with on-pump CABG in older patients with NSTE- Older patients with NSTE-ACS with diabetes mellitus had a greater survival advantage with CABG.529 Evaluation tools can help identify older patients with NSTE-ACS whose risk and comorbidity profile predict mortality within 6 to 12 months and possibly guide a palliative approach.524 See Online Data Supplement 24 for additional information on older patients.


Complications occur more frequently in older patients with Length of stay averages 6 days longer in older patients than in patients <50 years of age, and discharge (to home [52%]) is less frequent than in younger patients.557 In a metaanalysis, off-pump CABG appeared to offer a poten- tially safer and more effective revascularization technique compared with on-pump CABG in older patients with NSTE- Older patients with NSTE-ACS with diabetes mellitus had a greater survival advantage with CABG.529 Evaluation tools can help identify older patients with NSTE-ACS whose risk and comorbidity profile predict mortality within 6 to 12 months and possibly guide a palliative approach.524 See Online Data Supplement 24 for additional information on older patients. 7.2. HF: Recommendations Class I 1. Patients with a history of HF and NSTE-ACS should be treated according to the same risk stratification guidelines and recommendations for patients without (Level of Evidence: B) 2. Selection of a specific revascularization strategy should be based on the degree, severity, and extent of CAD; associated cardiac lesions; the extent of LV dysfunction; and the history of prior revascu- (Level of Evidence: B) In patients with HF and NSTE-ACS, the plan of care should be implemented as in patients without HF using medical therapy and an early invasive approach, because patients with abnormal LV function are at increased risk of mortality and HF itself may be associated with elevated serum troponin in the presence or absence of obstructive CAD. After angiography, risk stratification can be used to select revascu- larization strategies. The effect of surgical revascularization on improving survival has been most clearly demonstrated in patients with both extensive CAD and LV dysfunc- Such patients should undergo testing to iden- tify the severity and extent of ischemia and should in general be referred for coronary angiography.


The effect of surgical revascularization on improving survival has been most clearly demonstrated in patients with both extensive CAD and LV dysfunc- Such patients should undergo testing to iden- tify the severity and extent of ischemia and should in general be referred for coronary angiography. In selected patients with appropriate anatomy, PCI has been used.23,568 In patients who have already undergone CABG or in whom the anatomy is not favorable for CABG, PCI has been performed using CPG- based PCI performance strategies if specific targeted areas that are amenable to PCI can be identified.26 If there is a large amount of ischemic territory and very poor LV function, per- cutaneous ventricular assist devices or, in less severe cases, an IABP can be used for support during the procedure.266,569 573 See Online Data Supplement 25 for additional information on HF. Ventricular arrhythmias are common early after onset of NSTE-ACS, and not all require intervention. The mechanisms for these arrhythmias include continuing ischemia, hemody- namic and electrolyte abnormalities, reentry, and enhanced automaticity. Approximately 5% to 10% of hospitalized patients may develop ventricular tachycardia (VT)/ventricular fibrillation (VF), usually within 48 hours of presentation.574 The incidence of VF in otherwise uncomplicated AMI appears to have decreased within the past few years from >4% to <2%, of which 59% of patients had non Q-wave MI.574 A study of 277 consecutive patients with NSTE-ACS who under- went cardiac catheterization within 48 hours found VT/VF occurring in 7.6% of patients, 60% of which developed within 48 hours after admission.575 Risk factors for VT/VF include HF, hypotension, tachycardia, shock, and low TIMI flow grade. Treatment consists of immediate defibrillation or Table 11.


Approximately 5% to 10% of hospitalized patients may develop ventricular tachycardia (VT)/ventricular fibrillation (VF), usually within 48 hours of presentation.574 The incidence of VF in otherwise uncomplicated AMI appears to have decreased within the past few years from >4% to <2%, of which 59% of patients had non Q-wave MI.574 A study of 277 consecutive patients with NSTE-ACS who under- went cardiac catheterization within 48 hours found VT/VF occurring in 7.6% of patients, 60% of which developed within 48 hours after admission.575 Risk factors for VT/VF include HF, hypotension, tachycardia, shock, and low TIMI flow grade. Treatment consists of immediate defibrillation or Table 11. Summary of Recommendations for Special Patient Groups Recommendations COR LOE References NSTE-ACS in older patients Treat older patients ( 75 y of age) with GDMT, early invasive strategy, and revascularization as appropriate I A 515 519 Individualize pharmacotherapy in older patients, with dose adjusted by weight and/or CrCl to reduce adverse events caused by age-related changes in pharmacokinetics/dynamics, volume of distribution, comorbidity, drug interactions, and increased drug sensitivity Undertake patient-centered management for older patients, considering patient preferences/goals, comorbidities, functional and cognitive status, and life expectancy Bivalirudin rather than GP IIb/IIIa inhibitor plus UFH is reasonable for older patients ( 75 y of age), given similar efficacy but less bleeding risk It is reasonable to choose CABG over PCI in older patients, particularly those with DM or multivessel disease, because of the potential for improved survival and reduced CVD events IIa B 529 534 HF Treat patients with a history of HF according to the same risk stratification guidelines and recommendations for patients without HF Select a revascularization strategy based on the extent of CAD, associated cardiac lesions, LV dysfunction, and prior revascularization Cardiogenic shock Recommend early revascularization for cardiogenic shock due to cardiac pump failure I B 560, 588, 589 DM Recommend medical treatment and decisions for testing and revascularization similar to those for patients without DM Post CABG Recommend GDMT antiplatelet and anticoagulant therapy and early invasive strategy because of increased risk with prior CABG Perioperative NSTE-ACS Administer GDMT to perioperative patients with limitations imposed by noncardiac surgery I C 626, 627 Direct management at underlying cause of perioperative NSTE-ACS I C 21, 626 634 CKD Estimate CrCl and adjust doses of renally cleared medications according to pharmacokinetic data Administer adequate hydration to patients undergoing coronary and LV angiography I C N/A Invasive strategy is reasonable in patients with mild (stage 2) and moderate (stage 3) CKD IIa B 649 652 Women Manage women with the same pharmacological therapy as that for men for acute care and secondary prevention, with attention to weight and/or renally calculated doses of antiplatelet and anticoagulant agents to reduce bleeding risk I B 669 673 Early invasive strategy is recommended in women with NSTE-ACS and high-risk features (troponin positive) Myocardial revascularization is reasonable for pregnant women if ischemia-guided strategy is ineffective for management of life-threatening complications IIa C 674 Women with low-risk features (Section 3.3.1) should not undergo early invasive treatment because of lack of benefit and the possibility of harm Anemia, bleeding, and transfusion Evaluate all patients for risk of bleeding I C N/A Recommend that anticoagulant and antiplatelet therapy be weight-based where appropriate and adjusted for CKD to decrease the risk of bleeding There is no benefit of routine blood transfusion in hemodynamically stable patients with hemoglobin levels >8 g/dL III: No Benefit B 699 703 Cocaine and methamphetamine users Manage patients with recent cocaine or methamphetamine use similarly to those without cocaine- or methamphetamine-related NSTE-ACS.


The exception is in patients with signs of acute intoxication (eg, euphoria, tachycardia, and hypertension) and beta-blocker use unless patients are receiving coronary vasodilator therapy I C N/A (Continued) Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e385 cardioversion for VF or pulseless sustained VT. Early admin- istration of beta blockers has been associated with reduction in The prophylactic use of lidocaine is not rec- ommended. Although VT/VF is associated with higher 90-day mortality risk, premature ventricular contractions not associ- ated with hemodynamic compromise and accelerated ventric- ular rhythms do not confer higher mortality risks and do not require specific therapy other than maintaining electrolyte bal- ance. NSTE-ACS non-sustained VT occurring >48 hours after admission indicates an increased risk of cardiac and sudden death, especially when associated with accompanying myo- Life-threatening ventricular arrhythmias that occur >48 hours after NSTE-ACS are usually associated with LV dysfunction and signify poor prognosis. RCTs in patients with ACS have shown consistent benefit of implant- able cardioverter-defibrillator therapy for survivors of VT or For other at-risk patients, especially those with significantly reduced LVEF, candidacy for primary prevention of sudden cardiac death with an implantable cardioverter-defi- brillator should be readdressed 40 days after discharge.583 A life vest may be considered in the interim. AF, atrial flutter, and other supraventricular arrhythmias may be triggered by excessive sympathetic stimulation, atrial stress due to volume overload, atrial infarction, pericarditis, electrolyte abnormalities, hypoxia, or pulmonary disease. AF is the most common of these arrhythmias and may develop in >20% of patients.


AF is the most common of these arrhythmias and may develop in >20% of patients. AF is associated with shock, HF, stroke, and Management ofAF requires rate control and adequate anticoagulation according to the 2014 For hemodynamically unstable patients and those with continuing ischemia, treatment should be implemented according to the 2010 advanced cardiac life support CPGs.585 Cocaine and methamphetamine users (cont'd) It is reasonable to use benzodiazepines alone or in combination with NTG to manage hypertension and tachycardia and signs of acute cocaine or methamphetamine intoxication IIa C 741 744 Do not administer beta blockers to patients with recent cocaine or methamphetamine use who have signs of acute intoxication due to risk of potentiating coronary spasm III: Harm C N/A Vasospastic (Prinzmetal) angina Recommend CCBs alone or in combination with nitrates I B 753 758 Recommend HMG-CoA reductase inhibitor, cessation of tobacco use, and atherosclerosis risk factor modification I B 759 763 Recommend coronary angiography (invasive or noninvasive) for episodic chest pain with transient ST-elevation to detect severe CAD I C N/A Provocative testing during invasive coronary angiography* may be considered for suspected vasospastic angina when clinical criteria and noninvasive assessment fail to determine diagnosis IIb B 764 767 ACS with angiographically normal coronary arteries Invasive physiological assessment (coronary flow reserve measurement) may be considered with normal coronary arteries if endothelial dysfunction is suspected Stress (Takotsubo) cardiomyopathy Consider stress-induced cardiomyopathy in patients with apparent ACS and nonobstructive CAD I C N/A Perform ventriculography, echocardiography, or MRI to confirm or exclude diagnosis I B 795 798 Treat with conventional agents (ACE inhibitors, beta blockers, aspirin, and diuretics) if hemodynamically stable I C N/A Administer anticoagulant therapy for LV thrombi I C N/A It is reasonable to administer catecholamines for symptomatic hypotension in the absence of LV outflow tract obstruction IIa C N/A It is reasonable to use IABP for refractory shock IIa C N/A It is reasonable to use beta blockers and alpha-adrenergic agents for LV outflow tract obstruction IIa C N/A Prophylactic anticoagulation may be considered to prevent LV thrombi IIb C N/A *Provocative testing during invasive coronary angiography (eg, using ergonovine, acetylcholine, methylergonovine) is relatively safe, especially when performed in a controlled manner by experienced operators.


However, sustained spasm, serious arrhythmias, and even death can also occur but very infrequently. Therefore, provocative tests should be avoided in patients with significant left main disease, advanced 3-vessel disease, presence of high-grade obstructive lesions, significant valvular stenosis, significant LV systolic dysfunction, and advanced HF. ACE indicates angiotensin-converting enzyme; ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CAD, coronary artery disease; CCB, calcium channel blocker; CKD, chronic kidney disease; COR, Class of Recommendation; CrCl, creatinine clearance; CVD, cardiovascular disease; DM, diabetes mellitus; GDMT, guideline-directed medical therapy; GP, glycoprotein; HF, heart failure; IABP, intra-aortic balloon pump; LOE, Level of Evidence; LV, left ventricular; MRI, magnetic resonance imaging; N/A, not available; NSTE-ACS, non ST-elevation acute coronary syndrome; NTG, nitroglycerin; PCI, percutaneous coronary intervention; and UFH, unfractionated heparin. Table 11. Continued Recommendations COR LOE References Sinus bradycardia is especially common with inferior NSTEMI. Symptomatic or hemodynamically significant sinus bradycardia should be treated with atropine and, if not respon- sive, temporary pacing. The incidence of complete heart block is 1.0% to 3.7% in NSTEMI, based on anterior or posterior/ inferior location, respectively.586 Atrioventricular block and bun- dle-branch block develop in approximately 5% of patients.587 High-degree atrioventricular block or bundle-branch block in anterior NSTEMI is more ominous because of a greater extent of myocardial injury and involvement of the conduction system.587 First-degree atrioventricular block does not require treat- ment. High-grade atrioventricular block after inferior NSTEMI usually is transient, with a narrow QRS complex and a junctional escape rhythm that can be managed with an ischemia-guided strategy. Prophylactic placement of a tem- porary pacemaker is recommended for high-grade atrioven- tricular block, new bundle-branch block, or bifascicular block with anterior infarction. Indications for permanent pacing are reviewed in the 2012 device-based therapy CPG.20 7.2.2. Cardiogenic Shock: Recommendation Class I 1.


Indications for permanent pacing are reviewed in the 2012 device-based therapy CPG.20 7.2.2. Cardiogenic Shock: Recommendation Class I 1. Early revascularization is recommended in suitable patients with cardiogenic shock due to cardiac pump failure after NSTE-ACS.560,588,589 (Level of Evidence: B) AMI is the leading cause of cardiogenic shock. Early revascular- ization is a mainstay in the treatment of cardiogenic shock.560,589 Compared with medical therapy, early revascularization is asso- ciated with improved 6-month mortality560 and 13% absolute mortality reduction at 6 years.588 Urgent revascularization with CABG may be indicated for failed PCI, coronary anatomy not amenable to PCI, and at the time of surgical repair of a mechani- cal defect (eg, septal, papillary muscle, free-wall rupture). Age alone is not a contraindication to urgent revascularization for Mortality after cardiogenic shock has including in older adults,589,590 mortality ranging from approximately 40% with milder forms of to >45% with refractory shock.592 of patients in the IABP-SHOCK (Intra-Aortic Balloon Pump in Cardiogenic Shock) II trial presented with NSTEMI,268 of patients in the TRIUMPH (Tilarginine Acetate Injection in a Randomized International Study in Unstable Acute Myocardial Infarction PatientsWith Cardiogenic Shock) trial had ST depres- sion on presentation.592 Of the 23% of patients with ACS who had NSTEMI in the GRACE registry, 4.6% of patients experi- enced cardiogenic shock.593 Of the 2992 patients in shock, 57% underwent cardiac catheterization, and in-hospital revasculariza- tion was performed in 47% of this group.


Age alone is not a contraindication to urgent revascularization for Mortality after cardiogenic shock has including in older adults,589,590 mortality ranging from approximately 40% with milder forms of to >45% with refractory shock.592 of patients in the IABP-SHOCK (Intra-Aortic Balloon Pump in Cardiogenic Shock) II trial presented with NSTEMI,268 of patients in the TRIUMPH (Tilarginine Acetate Injection in a Randomized International Study in Unstable Acute Myocardial Infarction PatientsWith Cardiogenic Shock) trial had ST depres- sion on presentation.592 Of the 23% of patients with ACS who had NSTEMI in the GRACE registry, 4.6% of patients experi- enced cardiogenic shock.593 Of the 2992 patients in shock, 57% underwent cardiac catheterization, and in-hospital revasculariza- tion was performed in 47% of this group. In-hospital mortality of all patients with shock was 59%.594 Patients with NSTEMI developed cardiogenic shock later than patients with STEMI, and had higher-risk clinical character- istics, more extensive CAD, and more recurrent ischemia and infarction before developing shock compared with patients with STEMI, and shock developed later in patients with NSTEMI.151 Patients with NSTEMI constituted >17% of those in the SHOCK They were also older and had more comorbidi- ties but had comparable mortality to patients with STEMI.


In-hospital mortality of all patients with shock was 59%.594 Patients with NSTEMI developed cardiogenic shock later than patients with STEMI, and had higher-risk clinical character- istics, more extensive CAD, and more recurrent ischemia and infarction before developing shock compared with patients with STEMI, and shock developed later in patients with NSTEMI.151 Patients with NSTEMI constituted >17% of those in the SHOCK They were also older and had more comorbidi- ties but had comparable mortality to patients with STEMI. The left circumflex coronary artery was the culprit vessel in 30% of patients with NSTEMI, suggesting the presence of true poste- Dopamine in patients with cardiogenic shock may be associated with increased mortality compared with norepi- The use of percutaneous ventricular assist devices has been hampered by the need for interventional expertise, cost, and lack of supportive evidence.597 IABP has been used for and it may facilitate intervention in patients who are hemodynamically unstable, but it did not reduce mortality or secondary endpoints in 1 RCT of 598 patients with cardiogenic shock complicating AMI.268 Newer devices with higher levels of support have provided better hemodynamic support but without improved clinical outcomes compared with IABP.599,600 See Online Data Supplement 26 for additional information on cardiogenic shock. 7.3. Diabetes Mellitus: Recommendation Class I 1.


The left circumflex coronary artery was the culprit vessel in 30% of patients with NSTEMI, suggesting the presence of true poste- Dopamine in patients with cardiogenic shock may be associated with increased mortality compared with norepi- The use of percutaneous ventricular assist devices has been hampered by the need for interventional expertise, cost, and lack of supportive evidence.597 IABP has been used for and it may facilitate intervention in patients who are hemodynamically unstable, but it did not reduce mortality or secondary endpoints in 1 RCT of 598 patients with cardiogenic shock complicating AMI.268 Newer devices with higher levels of support have provided better hemodynamic support but without improved clinical outcomes compared with IABP.599,600 See Online Data Supplement 26 for additional information on cardiogenic shock. 7.3. Diabetes Mellitus: Recommendation Class I 1. Medical treatment in the acute phase of NSTE-ACS and decisions to perform stress testing, angiography, and re- vascularization should be similar in patients with and without diabetes mellitus.138,339,601 (Level of Evidence: A) CAD accounts for 75% of deaths in patients with diabetes mel- litus; >30% of patients with NSTE-ACS have diabetes mellitus; and patients with NSTE-ACS and diabetes mellitus have more adverse outcomes (eg, death, MI, readmission withACS, or HF) during follow up.593,602,603 The latter may be related to increased plaque instability and comorbidities, including hypertension, LV hypertrophy, cardiomyopathy, HF, and autonomic dysfunc- Patients with diabetes mellitus and ACS have longer delays from symptom onset to presentation,593,606,607 which may be attributable to their atypical symptoms. There is a U-shaped relationship between glucose levels and mortality in patients with diabetes mellitus and ACS.543 Both hyperglycemia and hypoglycemia have similar adverse effects on in-hospital and 6-month mortality.


There is a U-shaped relationship between glucose levels and mortality in patients with diabetes mellitus and ACS.543 Both hyperglycemia and hypoglycemia have similar adverse effects on in-hospital and 6-month mortality. The urgency to aggressively control blood glucose has been moderated by the results of the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regimen) trial.608 In this study of patients admitted to medical and surgical intensive care units, intensive glucose control (target 81 mg/dL to 108 mg/dL) resulted in increased all-cause mortality and hypoglycemia com- pared with moderate glucose control (target <l80 mg/dL). Blood glucose should be maintained at <l80 mg/dL while avoiding hypoglycemia. There is no established role for the administration of glucose-insulin-potassium infusions in NSTE-ACS.609 611 Although patients with diabetes mellitus and NSTE-ACS are at higher risk for in-hospital and longer-term events, they undergo less frequent revascularization procedures. In a mul- tinational study of 6385 patients with ACS, 25% of whom had diabetes mellitus, those with diabetes mellitus had more adverse risk profiles, more atypical presentations, longer treat- ment delays, more HF, and renal insufficiency but underwent less angiography and revascularization.607 In the GRACE and other studies,606 patients with diabetes melli- tus and NSTE-ACS in the United Kingdom603 had higher baseline risk profiles but received effective medical cardiac therapies and revascularization less frequently. Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e387 Although there are no RCTs of patients specifically diagnosed with diabetes mellitus andACS, there are ample data on patients with diabetes mellitus treated with PCI or CABG.564,565,613 615 The largest RCT, the FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease) trial,616 patients (approximately 30% with recent [interval unspecified] ACS) with 2- or 3-vessel CAD randomized to a DES or CABG.


Amsterdam et al 2014 AHA/ACC NSTE-ACS Guideline e387 Although there are no RCTs of patients specifically diagnosed with diabetes mellitus andACS, there are ample data on patients with diabetes mellitus treated with PCI or CABG.564,565,613 615 The largest RCT, the FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease) trial,616 patients (approximately 30% with recent [interval unspecified] ACS) with 2- or 3-vessel CAD randomized to a DES or CABG. At 5 years, there was a significant decrease in all-cause mortality (P=0.049; MI: P<0.001) associated with CABG. There was no specific analysis of outcomes in patients with recent (interval unspecified) ACS. CABG was also superior to PCI in reducing MACE in other trials564,613 615 (Appendix 4, Table D). The importance of the severity and complexity of CAD was underscoredintheSYNTAXtrial,inwhichthosewithlesssevere and complex CAD had similar outcomes with PCI and CABG compared with those with more severe and complex disease, in which CABG improved outcomes, including survival.355,565 7.3.1. Adjunctive Therapy A meta-analysis (6 trials: 23072 patients without diabetes mel- litus, 6458 patients with diabetes mellitus) of the effect of GP IIb/IIIa platelet receptor inhibitors (abciximab, eptifibatide, and tirofiban) on mortality in NSTEMI revealed that for the entire patient group, a GP IIb/IIIa inhibitor was associated with This benefit was particularly large in the 1279 patients with dia- betes mellitus who underwent PCI (4.0% to 1.2%; P=0.002). The ACUITY trial in ACS (13819 patients, 3852 with diabe- tes mellitus) reported that 30-day adverse clinical outcomes (death, MI, or unplanned revascularization) or major bleeding were increased in patients with diabetes mellitus (12.9% ver- Bivalirudin plus a GP IIb/IIIa inhibitor resulted in increased similar rates of the composite ischemia compared with heparin plus a GP IIb/IIIa inhibitor.