An additional bolus of 0.3 mg/kg can be given if needed. I B 248 Reduce infusion to 1 mg/kg/h with estimated CrCl <30 mL/min Preferred over UFH with GP IIb/IIIa receptor antagonist in patients at high risk of bleeding IIa B 248 Fondaparinux: Not recommended as sole anticoagulant for primary PCI III: Harm B 304 *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. Balloon angioplasty without stent placement may be used in selected patients. It might be reasonable to provide P2Y12 inhibitor therapy to patients with STEMI undergoing balloon angioplasty alone according to the recommendations listed for BMS. (LOE: C) The recommended ACT with planned GP IIb/IIIa receptor antagonist treatment is 200 to 250 s. The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250 to 300 s (HemoTec device) or 300 to 350 s (Hemochron device). ACT indicates activated clotting time; BMS, bare-metal stent; CrCl, creatinine clearance; COR, Class of Recommendation; DES, drug-eluting stent; GP, glycoprotein; IV, intravenous; LOE, Level of Evidence; N/A, not available; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction; TIA, transient ischemic attack; and UFH, unfractionated heparin. O Gara et al 2013 ACCF/AHA STEMI Guideline e377 2. After PCI, aspirin should be continued indefinite- (Level of Evidence: A) 3. A loading dose of a P2Y12 receptor inhibitor should be given as early as possible or at time of primary PCI to patients with STEMI. Options include a.


A loading dose of a P2Y12 receptor inhibitor should be given as early as possible or at time of primary PCI to patients with STEMI. Options include a. (Level of Evidence: B); or (Level of Evidence: B); or (Level of Evidence: B) inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (BMS or DES) during primary PCI using the following main- tenance doses: a. Clopidogrel 75 mg daily260,262 (Level of Evidence: B); or b. Prasugrel 10 mg daily262 (Level of Evidence: B); or c. Ticagrelor 90 mg twice a day.261 (Level of Evidence: B) Class IIa 1. It is reasonable to use 81 mg of aspirin in prefer- ence to higher maintenance doses after primary (Level of Evidence: B) 2. It is reasonable to begin treatment with an intrave- nous GP IIb/IIIa receptor antagonist such as abcix- (Level of Evidence: A), high-bolus-dose (Level of Evidence: B), or double-bolus (Level of Evidence: B) at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with STEMI who are receiving unfractionated heparin (UFH). Class IIb 1. It may be reasonable to administer intravenous GP IIb/IIIa receptor antagonist in the precatheteriza- tion laboratory setting (eg, ambulance, ED) to pa- tients with STEMI for whom primary PCI is intend- (Level of Evidence: B) 2. It may be reasonable to administer intracoronary ab- ciximab to patients with STEMI undergoing primary (Level of Evidence: B) 3. Continuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing DES place- ment. (Level of Evidence: C) Class III: Harm 1.


Continuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing DES place- ment. (Level of Evidence: C) Class III: Harm 1. Prasugrel should not be administered to patients with a history of prior stroke or transient ischemic (Level of Evidence: B) Although the minimum effective aspirin dose in the setting of PCI for STEMI has not been established prospectively, the writ- ing committee recommends that an empiric dose of 325 mg be given as early as possible before PCI and a maintenance dose continued indefinitely thereafter. It is the consensus of the writ- among patients who receive a stent during primary PCI. This The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. recommendation is based on evidence of an increased risk of bleeding in most studies comparing higher- with lower-dose as well as the absence of data from RCTs demonstrating superior efficacy of higher aspirin doses in this setting. However, because the CURRENT-OASIS 7 (Clopi- dogrel Optimal Loading Dose Usage to Reduce Recurrent Events Organization to Assess Strategies in Ischemic Syn- dromes) trial did not report differences in either efficacy or safety in patients with STEMI randomized to 81 mg versus 325 mg of aspirin, the committee did not think that the evi- dence favoring 81 mg over higher dosages was sufficiently conclusive to merit a Class I recommendation.253 Loading doses of P2Y12 inhibitors are provided before or at the time of primary PCI. These agents are continued in a maintenance dose for 1 year after PCI with a stent (BMS or DES) in the absence of bleeding.


These agents are continued in a maintenance dose for 1 year after PCI with a stent (BMS or DES) in the absence of bleeding. A 600-mg loading dose of clopidogrel is preferred to a 300-mg loading dose, given the more extensive and rapid platelet inhibition achieved with the higher dose, as well as the beneficial effects reported in a CURRENT-OASIS 7 subgroup analysis.259 The underpow- ered ARMYDA-6 MI (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty Myocardial Infarction) study also reported beneficial surrogate outcomes with the higher clopidogrel loading dose.258 The antiplatelet response to clopidogrel may vary as a function of patient phenotype (obesity, diabetes mellitus), enteric ABCB 1 polymorphisms, hepatic CYP450 enzyme system polymorphisms (predominantly CYP 2C19*2), and medications that interfere with clopidogrel biotransforma- tion. Approximately 25% to 30% of patients may harbor a reduced-function CYP2C19 allele. In TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis In Myocardial Infarction)285 patients who were carriers of the reduced-function CYP2C19*2 allele had significantly lower levels of the active metabolite of clopi- dogrel, diminished platelet inhibition, and increased rates of major adverse cardiovascular events and stent thrombosis.285 The US Food and Drug Administration has changed clopido- grel s prescribing information to highlight the potential impact of CYP2C19 genotype on clopidogrel pharmacokinetics and Nevertheless, other studies have not con- firmed associations between CYP2C19 polymorphisms and adverse outcomes in clopidogrel-treated patients.290 Future studies are needed to further clarify the risk associated with these genetic polymorphisms and to develop effective thera- peutic strategies for carriers of allelic variants of responsible enzyme systems.


In TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis In Myocardial Infarction)285 patients who were carriers of the reduced-function CYP2C19*2 allele had significantly lower levels of the active metabolite of clopi- dogrel, diminished platelet inhibition, and increased rates of major adverse cardiovascular events and stent thrombosis.285 The US Food and Drug Administration has changed clopido- grel s prescribing information to highlight the potential impact of CYP2C19 genotype on clopidogrel pharmacokinetics and Nevertheless, other studies have not con- firmed associations between CYP2C19 polymorphisms and adverse outcomes in clopidogrel-treated patients.290 Future studies are needed to further clarify the risk associated with these genetic polymorphisms and to develop effective thera- peutic strategies for carriers of allelic variants of responsible enzyme systems. Proton-pump inhibitors, most prominently omeprazole, can interfere with clopidogrel metabolism and result in diminished in vitro antiplatelet effect,291 but it does not appear that this pharmacokinetic effect translates into worse clinical outcomes.291,292 Prasugrel, an alternative thienopyridine, achieves greater inhibition of platelet aggregation than clopidogrel. In the of prasugrel versus clopidogrel in patients with ACS for whom an invasive strategy was planned, patientswithSTEMIwhowereassignedtoprasugrelhadalower 30-day rate of the composite primary outcome. This difference persisted to 15 months. In addition, the rate of stent thrombosis reported at 30 days was significantly lower with prasug- The loading dose of clopidogrel in TRITON-TIMI 38, which rarely was administered before coronary angiog- raphy and was limited to 300 mg, may have contributed to differences in efficacy and safety between treatment groups.262 The benefits of prasugrel relative to clopidogrel in STEMI must be weighed against the increase in the risk of bleeding associated with its use.


In addition, the rate of stent thrombosis reported at 30 days was significantly lower with prasug- The loading dose of clopidogrel in TRITON-TIMI 38, which rarely was administered before coronary angiog- raphy and was limited to 300 mg, may have contributed to differences in efficacy and safety between treatment groups.262 The benefits of prasugrel relative to clopidogrel in STEMI must be weighed against the increase in the risk of bleeding associated with its use. Prasugrel should not be administered to patients with a history of stroke or transient ischemic attack and was not shown to be beneficial in patients 75 years of age or patients who weigh <60 kg.260 In TRITON-TIMI 38, interaction testing for efficacy and safety showed no signifi- cant difference in bleeding risk across the spectrum of ACS. Prasugrel may be best suited for younger patients with diabe- tes mellitus or large areas of myocardium at risk, who are also at low bleeding risk, have the ability to continue a regimen of DAPT, and have no anticipation of surgery over the subse- quent 1 year. The package insert for prasugrel suggests that a lower maintenance dose of 5 mg daily might be considered for patients at high risk of bleeding, though this dose has not been Ticagrelor is a reversible, nonthienopyridine P2Y12 receptor antagonist that does not require metabolic conversion to active drug. The PLATO (Platelet Inhibition and Patient Outcomes) study compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) with clopidogrel (300- or 600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovas- cular events in 18624 patients with ACS, of whom 35% had Among the 7544 patients enrolled with ST eleva- tion or LBBB who underwent primary PCI, findings were consistent with the overall trial results.


The PLATO (Platelet Inhibition and Patient Outcomes) study compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) with clopidogrel (300- or 600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovas- cular events in 18624 patients with ACS, of whom 35% had Among the 7544 patients enrolled with ST eleva- tion or LBBB who underwent primary PCI, findings were consistent with the overall trial results. Significant reductions favoring ticagrelor were seen in the primary PCI subgroup for stent thrombosis and total deaths, though there were more strokes and episodes of ICH with ticagrelor.261 A prespecified subgroup analysis in the PLATO trial showed a significant interaction between treatment effect and geographic region, with an apparently smaller ticagrelor effect in North America than in other areas. Although this interaction could have been due to chance alone,295 a contribution from higher aspirin doses, as more commonly used in the United States, cannot be excluded. When provided long term with ticagrelor as a component of DAPT, the dose of aspirin should not exceed Although 1 year of DAPT is recommended after stent implantation during primary PCI for STEMI, earlier discon- tinuation of a P2Y12 inhibitor may be necessary if the risk of morbidity from bleeding outweighs the anticipated benefit of DAPT. Clinical judgment is required, and discussion with the interventional cardiologist is recommended.


Clinical judgment is required, and discussion with the interventional cardiologist is recommended. DAPT with aspirin and either clopidogrel or prasugrel has increased the risk of ICH in several clinical trials and patient populations (especially in those with prior stroke).260,296 298 In PLATO, the number of patients with prior stroke was small, limitingthepowertodetecttreatmentdifferencesinintracranial bleeding in this subgroup.299 Until further data become avail- able, it would seem prudent to weigh the possible increased risk of intracranial bleeding when the addition of ticagrelor to aspirin is considered in patients with prior stroke or transient Evidence to support the use of intravenous GP IIb/IIIa recep- tor antagonists in patients with STEMI was established largely before the use of oral DAPT. Although several studies have failed to show benefit with the administration of upstream GP IIb/IIIa receptor antagonists before primary PCI in the setting of DAPT with either UFH or bivalirudin anticoagula- a meta-analysis restricted to the use of abciximab has suggested it may be useful in this setting.277 The adjunctive use of GP IIb/IIIa agents at the time of PCI can be considered on an individual basis for large thrombus burden or inadequate receptor antagonist loading.265 270,301 For patients receiv- ing bivalirudin as the primary anticoagulant, routine adjunctive use of GP IIb/IIIa inhibitors is not recommended248 but may be considered as adjunctive or bail-out therapy in selected Studies of intracoronary GP IIb/IIIa administra- tion during primary PCI have shown mixed results for a variety of surrogate and combined clinical endpoints. Use of intracoro- nary abciximab may be reasonable in select cases.223,278 284 4.4.2. Anticoagulant Therapy to Support Primary PCI: Recommendations Class I 1.


Anticoagulant Therapy to Support Primary PCI: Recommendations Class I 1. For patients with STEMI undergoing primary PCI, the following supportive anticoagulant regimens are recommended: a. UFH, with additional boluses administered as needed to maintain therapeutic activated clotting time levels, taking into account whether a GP IIb/ IIIa receptor antagonist has been administered (Level of Evidence: C); or b. Bivalirudin with or without prior treatment with (Level of Evidence: B) Class IIa 1. In patients with STEMI undergoing PCI who are at high risk of bleeding, it is reasonable to use bivaliru- din monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist.248 (Level of Evidence: B) Class III: Harm 1. Fondaparinux should not be used as the sole antico- agulant to support primary PCI because of the risk of catheter thrombosis.304 (Level of Evidence: B) Intravenous UFH titrated to an appropriate activated clot- ting time is a familiar and well-tested strategy for anticoagu- lant therapy at the time of PCI for STEMI. Enoxaparin and fondaparinux have been studied less extensively in this set- ting.


Enoxaparin and fondaparinux have been studied less extensively in this set- ting. The ATOLL (Acute STEMI Treated with Primary PCI and IV Enoxaparin or UFH to Lower Ischemic and Bleeding Events at Short- and Long-term Follow-up) trial comparing intravenous enoxaparin with UFH for primary PCI failed to meet its primary, composite endpoint.305 Fondaparinux has been associated with catheter thrombosis in this set- On the basis of the findings in the HORIZONS- O Gara et al 2013 ACCF/AHA STEMI Guideline e379 AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial,248 the writing committee considers bivalirudin, in combination with oral DAPT, a reasonable anticoagulant alternative for primary PCI in STEMI, regardless of whether pretreatment was given with UFH, especially for patients at higher risk of bleeding and when avoidance of GP IIb/IIIa antagonists is desired. Bivali- rudin in this setting may provide a long-term survival benefit related to decreased bleeding but with a higher risk of early 5. Reperfusion at a Non PCI-Capable Hospital 5.1. Fibrinolytic Therapy When There Is an Anticipated Delay to Performing Primary PCI Within 120 Minutes of FMC: Recommendations See Table 4 for a summary of recommendations from this section. Class I 1. In the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previ- ous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of (Level of Evidence: A) Class IIa 1. In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability. (Level of Evidence: C) Class III: Harm 1.


In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability. (Level of Evidence: C) Class III: Harm 1. Fibrinolytic therapy should not be administered to patients with ST depression except when a true pos- terior (inferobasal) MI is suspected or when associ- ated with ST elevation in lead aVR.10,11,81,312,313 (Level of Evidence: B) 5.1.1. Timing of Fibrinolytic Therapy The benefits of fibrinolytic therapy in patients with ST eleva- tion or bundle-branch block MI are well established, with a time-dependent reduction in both mortality and morbidity rates during the initial 12 hours after symptom onset.81,306 As noted in Section 3.2, even when interhospital trans- port times are short, there may be advantages to the immediate delivery of fibrinolytic therapy versus any delay to primary PCI for patients with STEMI and low bleeding risk who pres- ent within the first 1 to 2 hours of symptom onset.123,321 Benefit from fibrinolytic therapy in patients who present >12 hours after symptom onset has not been established,81,307,309,322,323 although there remains consensus that consideration should be given to administering a fibrinolytic agent in symptom- atic patients presenting >12 hours after symptom onset with STEMI and a large area of myocardium at risk or hemody- namic instability if PCI is unavailable.4,48 5.1.2. Choice of Fibrinolytic Agent Fibrin-specific agents are preferred when available. Adjunc- tive antiplatelet and/or anticoagulant therapies are indicated, regardless of the choice of fibrinolytic agent. Table 4.


Adjunc- tive antiplatelet and/or anticoagulant therapies are indicated, regardless of the choice of fibrinolytic agent. Table 4. Indications for Fibrinolytic Therapy When There Is a >120-Minute Delay From FMC to Primary PCI (Figure 2) COR LOE References Ischemic symptoms <12 h I A 81, 306 311 Evidence of ongoing ischemia 12 to 24 h after symptom onset, and a large area of myocardium at risk or hemodynamic instability IIa C N/A ST depression except if true posterior (inferobasal) MI suspected or when associated with ST-elevation in lead aVR COR indicates Class of Recommendation; FMC, first medical contact; LOE, Level of Evidence; MI, myocardial infarction; N/A, not available; and PCI, percutaneous coronary intervention. Table 5. Fibrinolytic Agents Fibrinolytic Agent Dose Fibrin Specificity* Antigenic Patency Rate Fibrin-specific: Tenecteplase (TNK-tPA) Single IV weight-based bolus ++++ No 85%328 Reteplase (rPA) 10 U + 10-U IV boluses given 30 min apart ++ No 84%314 Non fibrin-specific: Streptokinase 1.5 million units IV given over 30 60 min No Yes 60% to 68%324, 329 *Strength of fibrin specificity; ++++ is more strong, ++ is less strong. 30 mg for weight <60 kg; 35 mg for 60 69 kg; 40 mg for 70 79 kg; 45 mg for 80 89 kg; and 50 mg for 90 kg. Bolus 15 mg, infusion 0.75 mg/kg for 30 min (maximum 50 mg), then 0.5 mg/kg (maximum 35 mg) over the next 60 min; total dose not to exceed 100 mg. Streptokinase is no longer marketed in the United States but is available in other countries. Streptokinase is highly antigenic and absolutely contraindicated within 6 mo of previous exposure because of the potential for serious allergic reaction. IV indicates intravenous; rPA, reteplase plasminogen activator; TIMI, Thrombolysis In Myocardial Infarction; TNK-tPA, tenecteplase tissue-type plasminogen activator; and tPA, tissue-type plasminogen activator. 5.1.3.


IV indicates intravenous; rPA, reteplase plasminogen activator; TIMI, Thrombolysis In Myocardial Infarction; TNK-tPA, tenecteplase tissue-type plasminogen activator; and tPA, tissue-type plasminogen activator. 5.1.3. Contraindications and Complications With Fibrinolytic Therapy Absolute and relative contraindications to fibrinolytic therapy are listed in Table 6. The decision to use fibrinolytic therapy for patients with STEMI is predicated on a risk benefit analy- sis that integrates time from onset of symptoms, the clinical and hemodynamic features at presentation, patient comorbidi- ties, risk of bleeding, presence of contraindications, and time delay to PCI (Section 3.2). 5.1.4. Adjunctive Antithrombotic Therapy With Fibrinolysis See Table 7 for a summary of recommendations from this section. 5.1.4.1. Adjunctive Antiplatelet Therapy With Fibrinolysis: Recommendations Class I 1. Aspirin (162- to 325-mg loading dose) and clopi- dogrel (300-mg loading dose for patients 75 years of age, 75-mg dose for patients >75 years of age) should be administered to patients with STEMI who receive fibrinolytic therapy.308,330,331 (Level of Evidence: A) 2. Aspirin should be continued indefinitely308,330,331 (Level of Evidence: A) and clopidogrel (75 mg daily) should be continued for at least 14 days330,331 (Level of Evidence: A) and up to 1 year (Level of Evidence: C) in patients with STEMI who receive fibrinolytic therapy. Class IIa 1. It is reasonable to use aspirin 81 mg per day in pref- erence to higher maintenance doses after fibrinolytic (Level of Evidence: B) The beneficial effects of aspirin and clopidogrel with fibrino- lytic therapy are well established.254,257,263,264 These agents should be given before or with the fibrinolytic.330 The recommendation that clopidogrel be continued for up to 1 year is extrapolated from the experience with DAPT in patients with non ST-elevation ACS.330 The coadministra- tion of other P2Y12 antagonists with fibrinolytic therapy has not been prospectively studied. 5.1.4.2. Adjunctive Anticoagulant Therapy With Fibrinolysis: Recommendations Class I 1.


5.1.4.2. Adjunctive Anticoagulant Therapy With Fibrinolysis: Recommendations Class I 1. Patients with STEMI undergoing reperfusion with fi- brinolytic therapy should receive anticoagulant ther- apy for a minimum of 48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization if performed.318,332 (Level of Evidence: A) Recommended regimens include a. UFH administered as a weight-adjusted intravenous bolus and infusion to obtain an activated partial thromboplastin time of 1.5 to 2.0 times control, for 48 hoursoruntilrevascularization.(LevelofEvidence:C); b. Enoxaparin administered according to age, weight, and creatinine clearance, given as an intravenous bolus, followed in 15 minutes by subcutaneous in- jection for the duration of the index hospitaliza- tion, up to 8 days or until revascularization.332 335 (Level of Evidence: A); or c. Fondaparinux administered with initial intrave- nous dose, followed in 24 hours by daily subcuta- neous injections if the estimated creatinine clear- ance is greater than 30 mL/min, for the duration of the index hospitalization, up to 8 days or until (Level of Evidence: B) Anticoagulation is recommended in support of fibrin-specific therapy to improve vessel patency and prevent reocclusion.336 Dosing of UFH is predicated on the activated partial throm- boplastin time, and monitoring of platelet counts to avoid the risks of excess bleeding and heparin-induced thrombocytopenia (HIT) is advised.318,337 339 UFH may be given as an intravenous bolus and infusion for patients receiving streptokinase if they are at high risk for systemic embolization. Enoxaparin is pre- ferred over UFH for anticoagulation extending beyond 48 hours. Caution is advised when enoxaparin is administered to patients Table 6.


Caution is advised when enoxaparin is administered to patients Table 6. Contraindications and Cautions for Fibrinolytic Therapy in STEMI* Absolute contraindications Any prior ICH Known structural cerebral vascular lesion (eg, arteriovenous malformation) Known malignant intracranial neoplasm (primary or metastatic) Ischemic stroke within 3 mo EXCEPT acute ischemic stroke within 4.5 h Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Significant closed-head or facial trauma within 3 mo Intracranial or intraspinal surgery within 2 mo Severe uncontrolled hypertension (unresponsive to emergency therapy) For streptokinase, prior treatment within the previous 6 mo Relative contraindications History of chronic, severe, poorly controlled hypertension Significant hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg) History of prior ischemic stroke >3 mo Dementia Known intracranial pathology not covered in absolute contraindications Traumatic or prolonged (>10 min) CPR Major surgery (<3 wk) Recent (within 2 to 4 wk) internal bleeding Noncompressible vascular punctures Pregnancy Active peptic ulcer Oral anticoagulant therapy *Viewed as advisory for clinical decision making and may not be all-inclusive or definitive. CPR indicates cardiopulmonary resuscitation; DBP; diastolic blood pressure; ICH, intracranial hemorrhage; SBP, systolic blood pressure; and STEMI, ST- elevation myocardial infarction. O Gara et al 2013 ACCF/AHA STEMI Guideline e381 with impaired renal function.340 Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI and is contraindicated for patients with a creatinine clearance <30 Bivalirudin may be used for patients treated with a fibrinolytic agent who develop HIT and require continued 5.2.


O Gara et al 2013 ACCF/AHA STEMI Guideline e381 with impaired renal function.340 Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI and is contraindicated for patients with a creatinine clearance <30 Bivalirudin may be used for patients treated with a fibrinolytic agent who develop HIT and require continued 5.2. Assessment of Reperfusion After Fibrinolysis TIMI 3 flow after fibrinolytic therapy predicts subsequent short- and long-term survival.343 345 Traditional variables that have been used to assess the angiographic response to fibrinolytic therapy are imprecise346 and have included an improvement in or relief of chest pain, resolution of ST elevation, and the pres- ence of reperfusion arrhythmias (eg, accelerated idioventricular rhythm). The relatively sudden and complete relief of chest pain coupled with >70% ST resolution (in the index lead showing the greatest degree of elevation on presentation) is highly sugges- tive of restoration of normal myocardial blood flow. Complete (or near complete) ST-segment resolution at 60 or 90 minutes after fibrinolytic therapy is a useful marker of a patent infarct Conversely, partial or absent improvement in the extent of ST elevation is not as accurate in predicting a closed Lack of improvement in ST resolution is associ- ated with worse prognosis.349,352,353 The combination of <50% ST resolution and the absence of reperfusion arrhythmias at 2 hours after treatment predicts TIMI flow <3 in the infarct artery with a sensitivity of 81%, specificity 88%, positive predictive value 87%, and negative predictive value 83%.347 Lack of resolution of ST elevation by at least 50% in the worst lead at 60 to 90 min- utes should prompt strong consideration of a decision to proceed with immediate coronary angiography and rescue PCI. 5.3. Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy See Figure 2. 5.3.1.


Transfer to a PCI-Capable Hospital After Fibrinolytic Therapy See Figure 2. 5.3.1. Transfer of Patients With STEMI to a PCI-Capable Hospital for Coronary Angiography After Fibrinolytic Therapy: Recommendations See Table 8 for a summary of recommendations from this section; Online Data Supplement 4 for additional data on early catheterization and rescue PCI for fibrinolytic failure in the stent era; and Online Data Supplement 5 for additional Table 7. Adjunctive Antithrombotic Therapy to Support Reperfusion With Fibrinolytic Therapy COR LOE References Antiplatelet therapy Aspirin 81- to 325-mg daily maintenance dose (indefinite) I A 308, 330, 331 81 mg daily is the preferred maintenance dose receptor inhibitors Clopidogrel: I A 330, 331 Age 75 y: 300-mg loading dose Followed by 75 mg daily for at least 14 d and up to 1 y in absence of bleeding I A (14 d) 330, 331 C (up to 1 y) N/A Age >75 y: no loading dose, give 75 mg I A 330, 331 Followed by 75 mg daily for at least 14 d and up to 1 y in absence of bleeding I A (14 d) 330, 331 C (up to 1 y) N/A Anticoagulant therapy UFH: I C N/A Weight-based IV bolus and infusion adjusted to obtain aPTT of 1.5 to 2.0 times control for 48 h or until revascularization. IV bolus of 60 U/kg (maximum 4000 U) followed by an infusion of 12 U/kg/h (maximum 1000 U) initially, adjusted to maintain aPTT at 1.5 to 2.0 times control (approximately 50 to 70 s) for 48 h or until revascularization.


IV bolus of 60 U/kg (maximum 4000 U) followed by an infusion of 12 U/kg/h (maximum 1000 U) initially, adjusted to maintain aPTT at 1.5 to 2.0 times control (approximately 50 to 70 s) for 48 h or until revascularization. Enoxaparin: I A 332 335 If age <75 y: 30-mg IV bolus, followed in 15 min by 1 mg/kg subcutaneously every 12 h (maximum 100 mg for the first 2 doses) If age 75 y: no bolus, 0.75 mg/kg subcutaneously every 12 h (maximum 75 mg for the first 2 doses) Regardless of age, if CrCl <30 mL/min: 1 mg/kg subcutaneously every 24 h Duration: For the index hospitalization, up to 8 d or until revascularization Fondaparinux: I B 304 Initial dose 2.5 mg IV, then 2.5 mg subcutaneously daily starting the following day, for the index hospitalization up to 8 d or until revascularization Contraindicated if CrCl <30 mL/min aPTT indicates activated partial thromboplastin time; COR, Class of Recommendation; CrCl, creatinine clearance; IV, intravenous; LOE, Level of Evidence; N/A, not available; and UFH, unfractionated heparin. data on early catheterization and PCI after fibrinolysis in the stent era. Class I 1. Immediate transfer to a PCI-capable hospital for coronary angiography is recommended for suitable patients with STEMI who develop cardiogenic shock or acute severe HF, irrespective of the time delay from MI onset.354 (Level of Evidence: B) Class IIa 1. Urgent transfer to a PCI-capable hospital for coro- nary angiography is reasonable for patients with STEMI who demonstrate evidence of failed reperfu- sion or reocclusion after fibrinolytic therapy.346,355 357 (Level of Evidence: B) 2. Transfer to a PCI-capable hospital for coronary an- giography is reasonable for patients with STEMI who have received fibrinolytic therapy even when hemodynamically stable and with clinical evidence of successful reperfusion.


Transfer to a PCI-capable hospital for coronary an- giography is reasonable for patients with STEMI who have received fibrinolytic therapy even when hemodynamically stable and with clinical evidence of successful reperfusion. Angiography can be per- formed as soon as logistically feasible at the receiv- ing hospital, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.358 363 (Level of Evidence: B) 5.3.1.1. Transfer for Cardiogenic Shock The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial354 demonstrated benefit with coronary angiography and emergency revascu- larization (with either PCI or CABG) compared with imme- diate medical stabilization and delayed revascularization in patients with ST-elevation/Q-wave or new LBBB MI and cardiogenic shock (Section 9.1.1). Of note, nearly 50% of patients randomized to the emergency revascularization arm received preprocedural fibrinolytic therapy, and the benefit of Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high- grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia. emergency revascularization was similar for patients trans- ferred versus those admitted directly to a PCI-capable hospital. For patients with cardiogenic shock, the benefit of emergency revascularization was apparent across a very wide time win- dow, extending up to 54 hours after MI and 18 hours after Although PCI should be performed as soon as possible after MI and shock onset, the time window for benefit in this clinical context is more prolonged because of the ongo- ing downward ischemic spiral associated with shock. 5.3.1.2. Transfer for Failure of Fibrinolytic Therapy Several trials in the stent era and several meta-analyses have examined the role of PCI for fibrinolytic failure346,355 357,364 (Online Data Supplement 4).


Transfer for Failure of Fibrinolytic Therapy Several trials in the stent era and several meta-analyses have examined the role of PCI for fibrinolytic failure346,355 357,364 (Online Data Supplement 4). These studies report a trend toward a lower mortality rate and significantly lower rates of recurrent MI and HF among patients treated with rescue PCI for failed fibrinolysis. For example, in the REACT (Rapid Early Action for Coronary Treatment) study,355 who failed to demonstrate evidence of reperfusion at 90 min- utes by ECG criteria were randomized to 1 of 3 treatment arms: rescue PCI, conservative care, or repeat fibrinolytic therapy. The primary endpoint, a composite of death, rein- farction, stroke, or severe HF at 6 months, was significantly lower among patients randomized to rescue PCI than among those randomized to conservative care or repeat fibrinolysis (event-free survival rate: 84.6% versus 70.1% versus 68.7%, P=0.004). The benefit was driven primarily by a reduction in reinfarction; there was no significant survival benefit. Minor bleeding was significantly higher among patients ran- domized to rescue PCI; however, there were no differences in major bleeding among the 3 groups. Other studies have reported higher rates of periprocedural bleeding and stroke in patients undergoing rescue PCI than in patients treated The benefit of transferring a patient for PCI of a persistently occluded infarct artery likely would jus- tify these risks if cardiogenic shock, significant hypotension, severe HF, or ECG evidence of an extensive area of myo- cardial jeopardy (including an anterior infarction or inferior infarction with either right ventricular [RV] involvement or anterior precordial ST depression) is present. In these cir- cumstances, the benefits are greatest if PCI is initiated early after fibrinolytic failure.


In these cir- cumstances, the benefits are greatest if PCI is initiated early after fibrinolytic failure. On the other hand, conservative treatment might be reasonable in a patient with improving symptoms and a limited inferior infarction despite persis- tence of ST elevation. 5.3.1.3. Transfer for Routine Early Coronary Angiography After Fibrinolytic Therapy With the introduction of coronary stents and aggressive anti- platelet therapies, there has been renewed interest in imme- diate and early catheterization after fibrinolytic therapy. The advantage of this approach is that it can be initiated at non PCI-capable hospitals and affords the healthcare sys- tem additional time to arrange a nonemergency transfer for angiography and PCI. Routine referral for angiography with the intent to perform PCI is supported indirectly by retrospec- tive analyses from trials of fibrinolytic therapy that suggest that patients treated with PCI during the index hospitalization have a lower risk of recurrent MI and a lower 2-year mortality Table 8. Indications for Transfer for Angiography After Fibrinolytic Therapy COR LOE References Immediate transfer for cardiogenic shock or severe acute HF irrespective of time delay from MI onset I B 354 Urgent transfer for failed reperfusion or reocclusion IIa B 346, As part of an invasive strategy in stable* patients with PCI between 3 and 24 h after successful fibrinolysis IIa B 358 363 *Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia. COR indicates Class of Recommendation; HF, heart failure; LOE, Level of Evidence; MI, myocardial infarction; and PCI, percutaneous coronary intervention.


COR indicates Class of Recommendation; HF, heart failure; LOE, Level of Evidence; MI, myocardial infarction; and PCI, percutaneous coronary intervention. O Gara et al 2013 ACCF/AHA STEMI Guideline e383 The results of RCTs evaluating a strategy of routine catheterization after fibrinolysis are limited by small sample sizes or surrogate endpoints and have provided mixed results. Nevertheless, most trials have demonstrated improvement in clinical outcomes in patients transferred for early cath- eterization, most notably in higher-risk patients357 362,368 371 (Table 8 and Figure 3). In the GRACIA (Grup de Analisis de la Cardiopatia Isquemica Aguda) study,362 early catheteriza- tion within 6 to 24 hours of successful fibrinolysis in stable patients was compared with an ischemia-guided approach. It resulted in improved outcomes, including a significantly lower rate of death, reinfarction, or ischemia-driven revascu- larization at 1 year. The TRANSFER-AMI (Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction) study360 was the largest (n=1059) of the RCTs evaluating transfer for coronary angiography and revascularization among high-risk patients and showed a significant reduction in the combined primary endpoint of death, recurrent MI, recurrent ischemia, new or wors- ening HF, or shock at 30 days with immediate transfer for the angiography group compared with conservative care. The findings from this and other studies indicate that high- risk patients with STEMI appear to benefit from immediate transfer for early catheterization, compared with either an ischemia-guided approach or delayed routine catheterization The reported benefits relate to a reduction in the incidence of recurrent infarction or isch- emia, thus favoring earlier transfer and revascularization when possible.


The findings from this and other studies indicate that high- risk patients with STEMI appear to benefit from immediate transfer for early catheterization, compared with either an ischemia-guided approach or delayed routine catheterization The reported benefits relate to a reduction in the incidence of recurrent infarction or isch- emia, thus favoring earlier transfer and revascularization when possible. The NORDISTEMI (Norwegian Study on District Treatment of ST-Elevation Myocardial Infarction) investi- examined the effect of immediate routine trans- fer for catheterization versus a conservative strategy with either ischemia-guided treatment in the non PCI-capable hospital or transfer for rescue PCI. Although this study failed to demonstrate a significant difference between the 2 treatment groups in the incidence of the primary com- posite endpoint of death, recurrent MI, stroke, or new or recurrent ischemia at 1 year, the incidence of death, recur- rent MI, or stroke was significantly lower in the immediate- transfer group. Furthermore, the magnitude of reduction in risk was similar to that reported for high-risk patients in the In a meta-analysis359 that included 7 RCTs of early transfer for catheterization, a strategy of routine early catheterization after fibrinolysis was associated with a statistically significant reduction in the incidence of death or MI at 30 days and at 1 year, without an increase in the risk of major bleeding. This meta-analysis was based on a mixture of trials that random- ized high-risk patients360,361,369 and trials that did not mandate the inclusion of high-risk subjects.


This meta-analysis was based on a mixture of trials that random- ized high-risk patients360,361,369 and trials that did not mandate the inclusion of high-risk subjects. A meta-regression analy- sis investigating the relative benefit of an invasive strategy after fibrinolysis according to the baseline risk of the enrolled patients for each trial suggested a larger proportional benefit with early catheterization and PCI in trials enrolling higher- It is important to recognize that the clinical trials that have addressed routine invasive evaluation after initial pharmaco- Figure 3. Primary outcome of trials of routine versus ischemia-driven (or delayed) catheterization and PCI after fibrinolytic therapy. The Figure depicts the results of trials comparing routine early catheterization after fibrinolytic therapy with either an ischemia-driven approach or routine delayed catheterization. The y-axis represents the percentage of patients who experienced 1 of the clinical trial endpoints. The Figure includes the average (or median) time from fibrinolytic therapy to PCI, the number of patients randomized in each study, the type of patients enrolled in the study (all patients or high-risk patients), the duration of follow-up for the primary endpoint, and the composite primary endpoint for each trial. The darker bars represent patients who underwent routine early catheterization after fibrinolytic therapy. The lighter bars represent patients who underwent either an ischemia-guided or routine delayed catheterization approach.


The lighter bars represent patients who underwent either an ischemia-guided or routine delayed catheterization approach. arrhy indicates arrhythmia; CAPITAL-AMI, Combined Angioplasty and Pharmacological Intervention Versus Thrombolysis Alone in Acute Myocardial Infarction; CARESS-in-AMI, Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction; CHF, congestive heart failure; D, death; GRACIA, Grup de Analisis de la Cardiopatia Isquemica Aguda; MI, myocardial infarction; NORDISTEMI, Norwegian study on District treatment of ST-Elevation Myocardial Infarction; PCI, percutaneous coronary intervention; revasc, ischemia-driven revasculariza- tion; RI, recurrent ischemia; TLR, target-lesion revascularization; TRANSFER-AMI, Trial of Routine Angioplasty and Stenting after Fibri- nolysis to Enhance Reperfusion in Acute Myocardial Infarction; SIAM-3, Southwest German Interventional Study In Acute Myocardial Infarction; and WEST, Which Early ST-Elevated Myocardial Infarction Therapy.358,360 362,368 370 Reproduced with permission from Granger.370a logical management used a time window of 0 to 24 hours for the early invasive strategy, thus supporting earlier transfer after administration of fibrinolytic therapy even for patients without high-risk features. However, this time window likely was used in the trial designs to create the greatest possible dif- ference in outcome when compared with the control group (rather than an a priori expectation that the benefit would be driven entirely in <24 hours). The writing committee believes that there likely will be continued benefit even beyond 24 hours in those patients with a patent but stenotic infarct artery. In stable patients who are not transferred immediately, catheter- ization can be considered as part of a routine pharmacoinvasive or ischemia-guided approach >24 hours after administration of fibrinolytic therapy. Because of the associated increased bleeding risk, very early (<2 to 3 hours) catheterization after administration of fibrinolytic therapy with intent to perform revascularization should be reserved for patients with evidence of failed fibrinolysis and significant myocardial jeopardy for whom rescue PCI would be appropriate. 6.


Because of the associated increased bleeding risk, very early (<2 to 3 hours) catheterization after administration of fibrinolytic therapy with intent to perform revascularization should be reserved for patients with evidence of failed fibrinolysis and significant myocardial jeopardy for whom rescue PCI would be appropriate. 6. Delayed Invasive Management 6.1. Coronary Angiography in Patients Who Initially Were Managed With Fibrinolytic Therapy or Who Did Not Receive Reperfusion: Recommendations See Table 9 for a summary of recommendations from this section. Class I 1. Cardiac catheterization and coronary angiography with intent to perform revascularization should be performed after STEMI in patients with any of the following: a. Cardiogenic shock or acute severe HF that devel- ops after initial presentation215,354,372,373 (Level of Evidence: B); b. Intermediate- or high-risk findings on predis- charge noninvasive ischemia testing232,233 (Level of Evidence: B); or c. Myocardial ischemia that is spontaneous or pro- voked by minimal exertion during hospitalization. (Level of Evidence: C) Class IIa 1. Coronary angiography with intent to perform revas- cularization is reasonable for patients with evidence of failed reperfusion or reocclusion after fibrinolytic therapy. Angiography can be performed as soon as (Level of Evidence: B) 2. Coronary angiography is reasonable before hospi- tal discharge in stable patients with STEMI after successful fibrinolytic therapy. Angiography can be performed as soon as logistically feasible, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fibrino- (Level of Evidence: B) The indications for coronary angiography in patients man- aged with an initial noninvasive strategy are interwoven with the indications for revascularization (Sections 5.3 and 6.2). Survivors of STEMI with indicators of intermediate or high risk and those with recurrent ischemia or mechanical compli- cations should be considered for coronary angiography and revascularization.


Survivors of STEMI with indicators of intermediate or high risk and those with recurrent ischemia or mechanical compli- cations should be considered for coronary angiography and revascularization. In addition, when STEMI is suspected to have occurred by a mechanism other than thrombotic occlu- sion at the site of an atherosclerotic plaque, coronary angiog- raphy may be reasonable to provide diagnostic information and to direct specific therapy. Routine referral for angiography of patients after fibrinolytic therapy is discussed in Section 5.3. Coronary angiography in patients with evidence of failed reperfusion or reocclusion should be performed as soon as 6.2. PCI of an Infarct Artery in Patients Who Initially Were Managed With Fibrinolysis or Who Did Not Receive Reperfusion Therapy: Recommendations See Table 10 for a summary of recommendations from this section. Class I 1. PCI of an anatomically significant stenosis in the infarct artery should be performed in patients with suitable anatomy and any of the following: a. Cardiogenic shock or acute severe HF354 (Level of Evidence: B); b. Intermediate- or high-risk findings on predis- charge noninvasive ischemia testing232,233 (Level of Evidence: C); or c. Myocardial ischemia that is spontaneous or pro- voked by minimal exertion during hospitalization. (Level of Evidence: C) Table 9.


PCI of an anatomically significant stenosis in the infarct artery should be performed in patients with suitable anatomy and any of the following: a. Cardiogenic shock or acute severe HF354 (Level of Evidence: B); b. Intermediate- or high-risk findings on predis- charge noninvasive ischemia testing232,233 (Level of Evidence: C); or c. Myocardial ischemia that is spontaneous or pro- voked by minimal exertion during hospitalization. (Level of Evidence: C) Table 9. Indications for Coronary Angiography in Patients Who Were Managed With Fibrinolytic Therapy or Who Did Not Receive Reperfusion Therapy COR LOE References Cardiogenic shock or acute severe HF that develops after initial presentation Intermediate- or high-risk findings on predischarge noninvasive ischemia testing Spontaneous or easily provoked myocardial ischemia I C N/A Failed reperfusion or reocclusion after fibrinolytic therapy IIa B 346, Stable* patients after successful fibrinolysis, before discharge and ideally between 3 and IIa B 358 363, *Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high-grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia. COR indicates Class of Recommendation; HF, heart failure; LOE, Level of Evidence; and N/A, not available. Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high- grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia. O Gara et al 2013 ACCF/AHA STEMI Guideline e385 Class IIa 1. Delayed PCI is reasonable in patients with STEMI and evidence of failed reperfusion or reocclusion after fibrinolytic therapy. PCI can be performed as soon as logistically feasible at the receiving hospi- (Level of Evidence: B) 2. Delayed PCI of a significant stenosis in a patent infarct artery is reasonable in stable patients with STEMI af- ter fibrinolytic therapy.


Delayed PCI of a significant stenosis in a patent infarct artery is reasonable in stable patients with STEMI af- ter fibrinolytic therapy. PCI can be performed as soon as logistically feasible at the receiving hospital, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fi- (Level of Evidence: B) Class IIb 1. Delayed PCI of a significant stenosis in a patent in- farct artery greater than 24 hours after STEMI may be considered as part of an invasive strategy in sta- (Level of Evidence: B) Class III: No Benefit 1. Delayed PCI of a totally occluded infarct artery greater than 24 hours after STEMI should not be performed in asymptomatic patients with 1- or 2-ves- sel disease if they are hemodynamically and electri- cally stable and do not have evidence of severe isch- (Level of Evidence: B) Delayed PCI of the infarct artery is performed in patients treated with an initial noninvasive strategy (ie, with fibrinolysis or without reperfusion therapy) who become unstable because of the development of cardiogenic shock, acute severe HF, or unstable postinfarction angina, provided that invasive manage- ment is not considered futile or inappropriate.215,379 Delayed PCI also encompasses interventions performed for fibrinolytic or infarct artery reocclusion, as part of an invasive strategy for patients after successful fibrinolysis,359 361 and for patients who did not receive reperfusion therapy but who did demonstrate significant residual ischemia during hospitaliza- tion. The benefits of routine, ie, non ischemia-driven, PCI of an angiographically significant stenosis in a patent infarct artery >24 hours after STEMI are less well established.232,233,378 Delayed PCI of a totally occluded infarct artery >24 hours after STEMI should not be undertaken in clinically stable patients without evidence of severe ischemia.


The benefits of routine, ie, non ischemia-driven, PCI of an angiographically significant stenosis in a patent infarct artery >24 hours after STEMI are less well established.232,233,378 Delayed PCI of a totally occluded infarct artery >24 hours after STEMI should not be undertaken in clinically stable patients without evidence of severe ischemia. In OAT (Occluded Artery Trial), there was no difference in the composite end- point of death, reinfarction, or class IV HF at a median follow- up of 5.8 years between patients managed with PCI and those treated medically. Reinfarction rates tended to be higher in the 6.3. PCI of a Noninfarct Artery Before Hospital Discharge: Recommendations Class I 1. PCI is indicated in a noninfarct artery at a time sepa- rate from primary PCI in patients who have spon- taneous symptoms of myocardial ischemia. (Level of Evidence: C) Class IIa 1. PCI is reasonable in a noninfarct artery at a time separate from primary PCI in patients with inter- mediate- or high-risk findings on noninvasive test- (Level of Evidence: B) Multivessel coronary artery disease is present in 40% to 65% of patients presenting with STEMI who undergo primary PCI and is associated with adverse prognosis.381,382 Studies of staged PCI of noninfarct arteries have been nonrandomized in design and have varied with regard to the timing of PCI and duration of follow-up.


PCI is reasonable in a noninfarct artery at a time separate from primary PCI in patients with inter- mediate- or high-risk findings on noninvasive test- (Level of Evidence: B) Multivessel coronary artery disease is present in 40% to 65% of patients presenting with STEMI who undergo primary PCI and is associated with adverse prognosis.381,382 Studies of staged PCI of noninfarct arteries have been nonrandomized in design and have varied with regard to the timing of PCI and duration of follow-up. These variations have contributed to the dispa- rate findings reported, although there seems to be a clear trend toward lower rates of adverse outcomes when primary PCI is lim- ited to the infarct artery and PCI of a noninfarct artery is under- taken in staged fashion at a later time.216,224,225,383,384 The largest of these observational studies compared 538 patients undergo- ing staged multivessel PCI within 60 days of primary PCI with propensity-matched individuals who had culprit-vessel PCI Multivessel PCI was associated with a lower mortality rate at 1 year (1.3% versus 3.3%; P=0.04).A nonsignificant trend toward a lower mortality rate at 1 year was observed in the sub- set of 258 patients who underwent staged PCI during the initial Table 10.


These variations have contributed to the dispa- rate findings reported, although there seems to be a clear trend toward lower rates of adverse outcomes when primary PCI is lim- ited to the infarct artery and PCI of a noninfarct artery is under- taken in staged fashion at a later time.216,224,225,383,384 The largest of these observational studies compared 538 patients undergo- ing staged multivessel PCI within 60 days of primary PCI with propensity-matched individuals who had culprit-vessel PCI Multivessel PCI was associated with a lower mortality rate at 1 year (1.3% versus 3.3%; P=0.04).A nonsignificant trend toward a lower mortality rate at 1 year was observed in the sub- set of 258 patients who underwent staged PCI during the initial Table 10. Indications for PCI of an Infarct Artery in Patients Who Were Managed With Fibrinolytic Therapy or Who Did Not Receive Reperfusion Therapy COR LOE References Cardiogenic shock or acute severe HF I B 354 Intermediate- or high-risk findings on predischarge noninvasive ischemia testing I C 232, 233 Spontaneous or easily provoked myocardial ischemia I C N/A Patients with evidence of failed reperfusion or reocclusion after fibrinolytic therapy (as soon as possible) IIa B 344 347 Stable* patients after successful fibrinolysis, ideally between 3 and 24 h IIa B 358 363 Delayed PCI of a totally occluded infarct artery >24 h after STEMI in stable patients III: No Benefit B 213, 376 *Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high- grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia. COR indicates Class of Recommendation; HF, heart failure; LOE, Level of Evidence; N/A, not available; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction.


COR indicates Class of Recommendation; HF, heart failure; LOE, Level of Evidence; N/A, not available; PCI, percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. Although individual circumstances will vary, clinical stability is defined by the absence of low output, hypotension, persistent tachycardia, apparent shock, high- grade ventricular or symptomatic supraventricular tachyarrhythmias, and spontaneous recurrent ischemia. hospitalization for STEMI.216 Although fractional flow reserve is gests that determination of fractional flow reserve may be useful to assess the hemodynamic significance of potential target lesions in The writing committee encourages research into the benefit of PCI of noninfarct arteries in patients with multi- vessel disease after successful primary PCI (Section 12.6). 6.4. Adjunctive Antithrombotic Therapy to Support Delayed PCI After Fibrinolytic Therapy SeeTable11forasummaryofrecommendationsfromthissection. The selection of adjunctive antiplatelet and anticoagu- lant therapies for use during PCI after fibrinolytic ther- apy should take into account the fibrinolytic agent used, the time since its administration, and the antiplatelet and anticoagulant agents already administered. GP IIb/IIIa inhibi- tors should be used with great caution, if at all, after full-dose fibrinolytic therapy, because this combination is associ- ated with high rates of bleeding and ICH, particularly in the 6.4.1. Antiplatelet Therapy to Support PCI After Fibrinolytic Therapy: Recommendations Class I 1. After PCI, aspirin should be continued indefinite- (Level of Evidence: A) 2. Clopidogrel should be provided as follows: a. A 300-mg loading dose should be given before or at the time of PCI to patients who did not receive a previous loading dose and who are undergoing PCI Table 11. Adjunctive Antithrombotic Therapy to Support PCI After Fibrinolytic Therapy COR LOE References Antiplatelet therapy Aspirin 162- to 325-mg loading dose given with fibrinolytic agent (before PCI).


Adjunctive Antithrombotic Therapy to Support PCI After Fibrinolytic Therapy COR LOE References Antiplatelet therapy Aspirin 162- to 325-mg loading dose given with fibrinolytic agent (before PCI). (Section 5.1.4.1 and Table 7) 81 mg daily is the preferred daily maintenance dose IIa B 253, 259, 263, 264 receptor inhibitors Loading doses For patients who received a loading dose of clopidogrel with fibrinolytic therapy: Continue clopidogrel 75 mg daily without an additional loading dose I C 260, 262, 330, 331 For patients who have not received a loading dose of clopidogrel: If PCI is performed 24 h after fibrinolytic therapy: clopidogrel 300-mg loading dose before or at the time of PCI I C N/A If PCI is performed >24 h after fibrinolytic therapy: clopidogrel 600-mg loading dose before or at the time of PCI I C N/A If PCI is performed >24 h after treatment with a fibrin-specific agent or >48 h after a non fibrin-specific agent: prasugrel 60 mg at the time of PCI For patients with prior stroke/TIA: prasugrel III: Harm B 260 Maintenance doses and duration of therapy DES placed: Continue therapy for at least 1 y with: Prasugrel: 10 mg daily IIa B 260, 262 BMS* placed: Continue therapy for at least 30 d and up to 1 y with: Clopidogrel: 75 mg daily I C 330, 331 Prasugrel: 10 mg daily IIa B 260, 262 Anticoagulant therapy Continue UFH through PCI, administering additional IV boluses as needed to maintain therapeutic ACT depending on use of GP IIb/IIIa receptor antagonist I C N/A Continue enoxaparin through PCI: I B 332, 390 No additional drug if last dose was within previous 8 h 0.3-mg/kg IV bolus if last dose was 8 to 12 h earlier Fondaparinux: III: Harm C 304 As sole anticoagulant for PCI *Balloon angioplasty without stent placement may be used in selected patients.


(Section 5.1.4.1 and Table 7) 81 mg daily is the preferred daily maintenance dose IIa B 253, 259, 263, 264 receptor inhibitors Loading doses For patients who received a loading dose of clopidogrel with fibrinolytic therapy: Continue clopidogrel 75 mg daily without an additional loading dose I C 260, 262, 330, 331 For patients who have not received a loading dose of clopidogrel: If PCI is performed 24 h after fibrinolytic therapy: clopidogrel 300-mg loading dose before or at the time of PCI I C N/A If PCI is performed >24 h after fibrinolytic therapy: clopidogrel 600-mg loading dose before or at the time of PCI I C N/A If PCI is performed >24 h after treatment with a fibrin-specific agent or >48 h after a non fibrin-specific agent: prasugrel 60 mg at the time of PCI For patients with prior stroke/TIA: prasugrel III: Harm B 260 Maintenance doses and duration of therapy DES placed: Continue therapy for at least 1 y with: Prasugrel: 10 mg daily IIa B 260, 262 BMS* placed: Continue therapy for at least 30 d and up to 1 y with: Clopidogrel: 75 mg daily I C 330, 331 Prasugrel: 10 mg daily IIa B 260, 262 Anticoagulant therapy Continue UFH through PCI, administering additional IV boluses as needed to maintain therapeutic ACT depending on use of GP IIb/IIIa receptor antagonist I C N/A Continue enoxaparin through PCI: I B 332, 390 No additional drug if last dose was within previous 8 h 0.3-mg/kg IV bolus if last dose was 8 to 12 h earlier Fondaparinux: III: Harm C 304 As sole anticoagulant for PCI *Balloon angioplasty without stent placement may be used in selected patients. It might be reasonable to provide P2Y12 inhibitor therapy to patients with STEMI undergoing balloon angioplasty after fibrinolysis alone according to the recommendations listed for BMS.


It might be reasonable to provide P2Y12 inhibitor therapy to patients with STEMI undergoing balloon angioplasty after fibrinolysis alone according to the recommendations listed for BMS. (Level of Evidence: C) The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250-300 s (HemoTec device) or 300-350 s (Hemochron device). ACT indicates activated clotting time; BMS, bare-metal stent; COR, Class of Recommendation; DES, drug-eluting stent; GP, glycoprotein; IV, intravenous; LOE, Level of Evidence; N/A, not available; PCI, percutaneous coronary intervention; TIA, transient ischemic attack; and UFH, unfractionated heparin. O Gara et al 2013 ACCF/AHA STEMI Guideline e387 within 24 hours of receiving fibrinolytic therapy (Level of Evidence: C); b. A 600-mg loading dose should be given before or at the time of PCI to patients who did not receive a previous loading dose and who are undergoing PCI more than 24 hours after receiving fibrinolytic therapy (Level of Evidence: C); and c. A dose of 75 mg daily should be given after (Level of Evidence: C) Class IIa 1. After PCI, it is reasonable to use 81 mg of aspirin per day in preference to higher maintenance dos- (Level of Evidence: B) 2. Prasugrel, in a 60-mg loading dose, is reasonable once the coronary anatomy is known in patients who did not receive a previous loading dose of clopidogrel at the time of administration of a fibrinolytic agent, but prasugrel should not be given sooner than 24 hours after administration of a fibrin-specific agent or 48 hours after administration of a non fibrin-specific (Level of Evidence: B) 3. Prasugrel, in a 10-mg daily maintenance dose, is rea- sonable after PCI.260,262 (Level of Evidence: B) Class III: Harm 1.


Prasugrel, in a 10-mg daily maintenance dose, is rea- sonable after PCI.260,262 (Level of Evidence: B) Class III: Harm 1. Prasugrel should not be administered to patients with a history of prior stroke or transient ischemic (Level of Evidence: B) Patients with STEMI should receive clopidogrel at the time of administration of a fibrinolytic agent as a routine part of a pharmacological reperfusion strategy (Section 5.1). Clopido- grel then should be continued in uninterrupted fashion through and after PCI. The optimal loading dose of clopidogrel before or at the time of PCI in patients who may not have received it previously with fibrinolytic therapy is not known. In the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy Thrombolysis In Myocardial Infarction 28) trial,331 PCI was performed 2 to 8 days after fibrinolysis in about half of the enrolled patients, and open-label clopidogrel (300-mg loading dose, 75-mg maintenance dose) was administered after diagnostic angiography in patients undergoing infarct artery stenting. Treatment with clopidogrel significantly reduced the incidence of cardiovascular death, MI, or stroke (major sec- ondary composite endpoint) after PCI. In addition, there was no significant increase in the rates of TIMI major or minor bleeding with clopidogrel treatment. A subset of patients with STEMI in the TRITON-TIMI 38 trial received fibrinolytic therapy >24 hours (for fibrin-specific agents) or >48 hours (for non fibrin-specific agents) before PCI. In this subset, the use of prasugrel compared to clopidogrel was associated with a significantly lower rate of the primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (HR: TIMI major bleeding unrelated to CABG.262 Accordingly, pra- sugrel (60-mg loading dose) may be used as an alternative to clopidogrel in patients with STEMI who undergo delayed PCI after administration of a fibrinolytic agent. 6.4.2.


In this subset, the use of prasugrel compared to clopidogrel was associated with a significantly lower rate of the primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (HR: TIMI major bleeding unrelated to CABG.262 Accordingly, pra- sugrel (60-mg loading dose) may be used as an alternative to clopidogrel in patients with STEMI who undergo delayed PCI after administration of a fibrinolytic agent. 6.4.2. Anticoagulant Therapy to Support PCI After Fibrinolytic Therapy: Recommendations Class I 1. For patients with STEMI undergoing PCI after re- ceiving fibrinolytic therapy with intravenous UFH, additional boluses of intravenous UFH should be ad- ministered as needed to support the procedure, tak- ing into account whether GP IIb/IIIa receptor antag- onists have been administered. (Level of Evidence: C) 2. For patients with STEMI undergoing PCI after re- ceiving fibrinolytic therapy with enoxaparin, if the last subcutaneous dose was administered within the prior 8 hours, no additional enoxaparin should be given; if the last subcutaneous dose was administered between 8 and 12 hours earlier, enoxaparin 0.3 mg/ kg IV should be given.335,390 (Level of Evidence: B) Class III: Harm 1. Fondaparinux should not be used as the sole anticoag- ulant to support PCI.An additional anticoagulant with anti-IIa activity should be administered because of the risk of catheter thrombosis.304 (Level of Evidence: C) Anticoagulation should be continued through emergent or nonurgent PCI procedures performed during the index hospi- talization after initial use of fibrinolytic therapy. For patients who received UFH or enoxaparin with fibrinolytic therapy, these agents may be continued uninterrupted through the PCI Transitioning from enoxaparin to either UFH or bivalirudin is possible, provided the last enoxaparin dose was >12 hours before PCI. Similarly, UFH may be transitioned to bivalirudin for PCI.


For patients who received UFH or enoxaparin with fibrinolytic therapy, these agents may be continued uninterrupted through the PCI Transitioning from enoxaparin to either UFH or bivalirudin is possible, provided the last enoxaparin dose was >12 hours before PCI. Similarly, UFH may be transitioned to bivalirudin for PCI. Fondaparinux does not provide adequate anticoagulation for PCI, and additional intravenous boluses of UFH (or bivalirudin) should be administered.304 7. Coronary Artery Bypass Graft Surgery 7.1. CABG in Patients With STEMI: Recommendations Class I 1. Urgent CABG is indicated in patients with STEMI and coronary anatomy not amenable to PCI who have ongoing or recurrent ischemia, cardiogenic shock, severe HF, or other high-risk features.391 393 (Level of Evidence: B) 2. CABG is recommended in patients with STEMI at time of operative repair of mechanical defects.394 398 (Level of Evidence: B) Class IIa 1. The use of mechanical circulatory support is reason- able in patients with STEMI who are hemodynami- cally unstable and require urgent CABG. (Level of Evidence: C) Class IIb 1. Emergency CABG within 6 hours of symptom onset may be considered in patients with STEMI who do not have cardiogenic shock and are not candidates for PCI or fibrinolytic therapy. (Level of Evidence: C) CABG has a limited role in the acute phase of STEMI other than for cardiogenic shock, but it may be indicated for failed PCI, for coronary anatomy not amenable to PCI, and at the time of surgical repair of a mechanical defect, such as ventricular septal, papillary muscle, or free-wall rupture. Older case series highlighted a potential excess mortality risk for CABG when performed early after STEMI, which was related to worsen- ing myocardial injury from cardiopulmonary bypass, aortic cross-clamping, and cardioplegic arrest, with hemorrhagic transformation and infarct expansion.


Older case series highlighted a potential excess mortality risk for CABG when performed early after STEMI, which was related to worsen- ing myocardial injury from cardiopulmonary bypass, aortic cross-clamping, and cardioplegic arrest, with hemorrhagic transformation and infarct expansion. However, contemporary modifications to the standard operative approach, such as on- pump beating-heart surgery, off-pump techniques, or adjunctive temporary mechanical circulatory support devices, may lead to improved survival rates after CABG in the acute hospital phase. 7.2. Timing of Urgent CABG in Patients With STEMI in Relation to Use of Antiplatelet Agents: Recommendations Class I 1. Aspirin should not be withheld before urgent (Level of Evidence: C) 2. Clopidogrel or ticagrelor should be discontinued at least 24 hours before urgent on-pump CABG, if pos- (Level of Evidence: B) 3. Short-acting intravenous GP IIb/IIIa receptor antag- onists (eptifibatide, tirofiban) should be discontinued at least 2 to 4 hours before urgent CABG.405,406 (Level of Evidence: B) 4. Abciximab should be discontinued at least 12 hours before urgent CABG.362 (Level of Evidence: B) Class IIb 1. Urgent off-pump CABG within 24 hours of clopido- grel or ticagrelor administration might be consid- ered, especially if the benefits of prompt revascular- ization outweigh the risks of bleeding.401,407 409 (Level of Evidence: B) 2. Urgent CABG within 5 days of clopidogrel or ti- cagrelor administration or within 7 days of prasu- grel administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding.


Urgent CABG within 5 days of clopidogrel or ti- cagrelor administration or within 7 days of prasu- grel administration might be considered, especially if the benefits of prompt revascularization outweigh the risks of bleeding. (Level of Evidence: C) In contrast to previous observations410 412 of markedly increased rates of major bleeding and mediastinal reex- ploration after CABG in patients exposed to clopidogrel within 5 to 7 days before CABG, several reports have sug- gested that it might be reasonable to proceed with urgent surgery within a shorter time frame, especially when the benefits of revascularization outweigh the risks of bleeding, as often may be the case among patients with Shorter delays to urgent surgery may also be pos- sible when off-pump revascularization is planned. Among the 136 patients in CLARITY-TIMI 28 who underwent CABG within 5 days of clopidogrel exposure, there was no differ- ence in the rates of major bleeding through 30 days of follow- up between the clopidogrel and placebo groups (7.5% versus In a prospective RCT exam- ining the effect of the timing of clopidogrel discontinuation before CABG, 3 groups were studied: clopidogrel continued to the day of surgery, clopidogrel discontinued 3 days before surgery, and clopidogrel discontinued 5 days before surgery.


Among the 136 patients in CLARITY-TIMI 28 who underwent CABG within 5 days of clopidogrel exposure, there was no differ- ence in the rates of major bleeding through 30 days of follow- up between the clopidogrel and placebo groups (7.5% versus In a prospective RCT exam- ining the effect of the timing of clopidogrel discontinuation before CABG, 3 groups were studied: clopidogrel continued to the day of surgery, clopidogrel discontinued 3 days before surgery, and clopidogrel discontinued 5 days before surgery. Patients in the continuation group experienced increased rates of bleeding and blood product utilization, but the 3- and 5-day discontinuation groups had comparably low bleeding rates and blood product usage that resembled historical con- In a retrospective analysis of a nonrandomized subgroup of patients in the PLATO trial, in which several definitions of bleeding were used, no significant differences in CABG-related bleeding were observed between patients allocated ticagrelor and patients who received clopidogrel, and there were no observed differences in the rates of reop- In contrast, among the relatively few patients with STEMI in TRITON-TIMI 38 who underwent CABG during the 15-month course of the study, rates of TIMI major or minor bleeding after CABG were significantly higher with prasugrel The excess bleeding hazard observed with prasugrel should prompt consideration of an alternative antiplatelet strategy in patients with STEMI who may require urgent CABG during their index hospitalization. The timing of elective CABG in relation to the use of P2Y12 receptor antagonists is referenced in Section 4.1 of the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft 8. Routine Medical Therapies See Table 12 for a summary of selected routine medical therapies. 8.1. Beta Blockers: Recommendations Class I 1.


Routine Medical Therapies See Table 12 for a summary of selected routine medical therapies. 8.1. Beta Blockers: Recommendations Class I 1. Oral beta blockers should be initiated in the first 24 hours in patients with STEMI who do not have any of the following: signs of HF, evidence of a low output state, increased risk for cardiogenic shock, or other contraindications to use of oral beta blockers (PR in- terval more than 0.24 seconds, second- or third-de- gree heart block, active asthma, or reactive airways (Level of Evidence: B) 2. Beta blockers should be continued during and af- ter hospitalization for all patients with STEMI and with no contraindications to their use.417,418 (Level of Evidence: B) Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock) are age >70 years, systolic BP <120 mm Hg, sinus tachycardia >110 bpm or heart rate <60 bpm, and increased time since onset of symptoms of STEMI. O Gara et al 2013 ACCF/AHA STEMI Guideline e389 3. Patients with initial contraindications to the use of beta blockers in the first 24 hours after STEMI should be reevaluated to determine their subsequent eligibility. (Level of Evidence: C) Class IIa 1. It is reasonable to administer intravenous beta blockers at the time of presentation to patients with STEMI and no contraindications to their use who are hypertensive or have ongoing ischemia.414 416 (Level of Evidence: B) The efficacy and safety of the early routine use of intravenous beta blockers were examined in COMMIT/CCS-2 (Clopi- dogrel and Metoprolol in Myocardial Infarction Trial).414 Early intravenous metoprolol followed by high-dose oral therapy had a neutral effect on the combined endpoint of death, recurrent MI, or cardiac arrest.


It is reasonable to administer intravenous beta blockers at the time of presentation to patients with STEMI and no contraindications to their use who are hypertensive or have ongoing ischemia.414 416 (Level of Evidence: B) The efficacy and safety of the early routine use of intravenous beta blockers were examined in COMMIT/CCS-2 (Clopi- dogrel and Metoprolol in Myocardial Infarction Trial).414 Early intravenous metoprolol followed by high-dose oral therapy had a neutral effect on the combined endpoint of death, recurrent MI, or cardiac arrest. There were lower rates of recurrent MI and VF in the treated group, outcomes that were balanced by a significantly higher rate of cardiogenic shock with metoprolol, especially on days 0 and 1. The like- lihood of developing cardiogenic shock was increased in certain subgroups, including patients with age >70 years, Table 12.


The like- lihood of developing cardiogenic shock was increased in certain subgroups, including patients with age >70 years, Table 12. Selected Routine Medical Therapies Therapy Indications Dose/Administration Avoid/Caution Beta-Receptor Antagonists Oral: All patients without contraindication IV: Patients with refractory hypertension or ongoing ischemia without contraindication Individualize: Metoprolol tartrate 25 to 50 mg every 6 to 12 h orally, then transition over next 2 to 3 d to twice-daily dosing of metoprolol tartrate or to daily metoprolol succinate; titrate to daily dose of 200 mg as tolerated Carvedilol 6.25 mg twice daily, titrate to 25 mg twice daily as tolerated Metoprolol tartrate IV 5 mg every 5 min as tolerated up to 3 doses; titrate to heart rate and BP Signs of HF Low output state Increased risk of cardiogenic shock Prolonged first-degree or high-grade AV block Reactive airways disease ACE Inhibitors For patients with anterior infarction, post-MI LV systolic dysfunction (EF 0.40) or HF May be given routinely to all patients without contraindication Individualize: Lisinopril 2.5 to 5 mg/d to start; titrate to 10 mg/d or higher as tolerated Captopril 6.25 to 12.5 mg 3 times/d to start; titrate to 25 to 50 mg 3 times/d as tolerated Ramipril 2.5 mg twice daily to start; titrate to 5 mg twice daily as tolerated Trandolapril test dose 0.5 mg; titrate up to 4 mg daily as tolerated Hypotension Renal failure Hyperkalemia ARB For patients intolerant of ACE inhibitors Valsartan 20 mg twice daily to start; titrate to 160 mg twice daily as tolerated Hypotension Renal failure Hyperkalemia Statins All patients without contraindications High-dose atorvastatin 80 mg daily Caution with drugs metabolized via CYP3A4, fibrates Monitor for myopathy, hepatic toxicity Combine with diet and lifestyle therapies Adjust dose as dictated by targets for LDL cholesterol and non HDL cholesterol reduction Nitroglycerin Ongoing chest pain Hypertension and HF 0.4 mg sublingual every 5 min up to 3 doses as BP allows IV dosing to begin at 10 mcg/min; titrate to desired BP effect Avoid in suspected RV infarction Avoid with SBP <90 mmHg or if SBP >30 mmHg below baseline Avoid if recent (24 to 48 h) use of Oxygen Clinically significant hypoxemia (oxygen saturation <90%) HF Dyspnea 2 to 4 L/min via nasal cannula Increase rate or change to face mask as needed Caution with chronic obstructive pulmonary disease and CO2 retention Morphine Pain Anxiety Pulmonary edema 4 to 8 mg IV initially, with lower doses in elderly 2 to 8 mg IV every 5 to 15 min if needed Lethargic or moribund patient Hypotension Bradycardia Known hypersensitivity ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; AV, atrioventricular; BP, blood pressure; CO2 , carbon dioxide; EF, ejection fraction; HDL, high-density lipoprotein; HF, heart failure; IV, intravenous; LDL, low-density lipoprotein; LV, left ventricular; MI, myocardial infarction; RV, right ventricular; and SBP, systolic blood pressure.


systolic BP <120 mmHg, presenting heart rate >110 bpm, or increased time since onset of symptoms of STEMI. The benefit of beta blockers for secondary prevention has been established in numerous trials conducted in the prereperfu- sion era and appears to be greatest for patients with MI com- plicated by HF, LV dysfunction, or ventricular arrhythmias.418 The long-term duration of routine beta-blocker therapy after uncomplicated MI in patients without HF or hypertension has not been prospectively addressed. AHA/ACCF secondary prevention guidelines recommend a 3-year treatment course in this patient subset.257 8.2. Renin-Angiotensin-Aldosterone System Inhibitors: Recommendations Class I 1. An angiotensin-converting enzyme (ACE) inhibitor should be administered within the first 24 hours to all patients with STEMI with anterior location, HF, or ejection fraction (EF) less than or equal to 0.40, (Level of Evidence: A) 2. An angiotensin receptor blocker (ARB) should be given to patients with STEMI who have indications for but are intolerant of ACE inhibitors.424,425 (Level of Evidence: B) 3. An aldosterone antagonist should be given to pa- tients with STEMI and no contraindications who are already receiving an ACE inhibitor and beta blocker and who have an EF less than or equal to 0.40 and either symptomatic HF or diabetes mellitus.426 (Level of Evidence: B) Class IIa 1. ACE inhibitors are reasonable for all patients with STEMI and no contraindications to their use.427 429 (Level of Evidence: A) Oral ACE inhibitors reduce fatal and nonfatal major cardiovascular events in patients with STEMI.360,361,420,422,428 Their protective effects have been demonstrated indepen- dent of the use of other pharmacotherapies (ie, fibrinolytics, aspirin, and beta blockers).


ACE inhibitors are reasonable for all patients with STEMI and no contraindications to their use.427 429 (Level of Evidence: A) Oral ACE inhibitors reduce fatal and nonfatal major cardiovascular events in patients with STEMI.360,361,420,422,428 Their protective effects have been demonstrated indepen- dent of the use of other pharmacotherapies (ie, fibrinolytics, aspirin, and beta blockers). The magnitude of clinical benefit is greatest in high-risk patient subgroups (ie, anterior MI, EF 0.40, HF, prior MI, and tachycardia).431 Demonstra- tion of an early benefit (within the first 24 hours) supports the prompt use of these agents in patients without existing contraindications (hypotension, shock, bilateral renal artery stenosis or history of worsening of renal function with ACE inhibitor/ARB exposure, renal failure, or drug allergy). The role of routine long-term ACE inhibitor therapy in low- risk patients after STEMI who have been revascularized and treated with aggressive lipid-lowering therapies is less ARBs are indicated for ACE inhibitor intolerant patients. Specifically, valsartan was found to be noninferior to captopril in the VALIANT (Valsartan in Acute Myocardial The EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival) study estab- lished the benefit of an aldosterone antagonist, eplerenone, added to optimal medical therapy in eligible patients (creati- nine 2.5 mg/dL in men and 2.0 mg/dL in women, potas- sium 5.0 mEq/L) 3 to 14 days after STEMI with EF 0.40 and either symptomatic HF or diabetes mellitus.426 A post hoc analysis of the EPHESUS trial suggested a time-dependent treatment effect of eplerenone. Earlier initiation of the drug (<7 days) significantly reduced the rates of all-cause mortal- ity, sudden cardiac death (SCD), and cardiovascular mortality/ hospitalization, whereas initiation 7 days had no significant effect on outcomes.433 8.3. Lipid Management: Recommendations Class I 1.


Earlier initiation of the drug (<7 days) significantly reduced the rates of all-cause mortal- ity, sudden cardiac death (SCD), and cardiovascular mortality/ hospitalization, whereas initiation 7 days had no significant effect on outcomes.433 8.3. Lipid Management: Recommendations Class I 1. High-intensity statin therapy should be initiated or continued in all patients with STEMI and no contra- indications to its use.434 436 (Level of Evidence: B) Class IIa 1. It is reasonable to obtain a fasting lipid profile in patients with STEMI, preferably within 24 hours of presentation.


It is reasonable to obtain a fasting lipid profile in patients with STEMI, preferably within 24 hours of presentation. (Level of Evidence: C) Treatment with statins in patients stabilized after an ACS, including STEMI, lowers the risk of coronary heart disease death, recurrent MI, stroke, and the need for coronary revas- More intensive statin therapy, compared with less intensive therapy, appears to be associated with an additional lowering of nonfatal clinical endpoints.434,436,439 Among currently available statins, only high-dose atorvas- tatin (80 mg daily) has been shown to reduce death and isch- emic events among patients with ACS.436,440 Approximately one third of patients in the PROVE-IT TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy Throm- bolysis in Myocardial Infarction 22) trial had STEMI.436 Car- diovascular event rates were not significantly reduced with a tiered strategy of simvastatin (40 mg daily for 1 month followed by 80 mg daily) in the A to Z Trial (Aggrastat to and concerns have been raised recently about the safety of high-dose simvastatin (ie, 80 mg daily).441 Although the benefit of high-intensity statins declines among statin- na ve patients with ACS as a function of decreasing low-den- sity lipoprotein levels,442 the writing committee recommends the use of statins in all patients with STEMI.435 Statin therapy after ACS is beneficial even in patients with baseline low- density lipoprotein cholesterol levels <70 mg/dL.443 Trials of statin therapy in patients with ACS and stable ischemic heart disease have been designed to compare either more intensive versus less intensive statin treatment or active statin versus They have not been designed to compare clini- cal outcomes as a function of the specific low-density lipo- protein cholesterol level achieved with treatment. Improved compliance with therapy is a strong rationale for timing the initiation of lipid-lowering drug therapy before discharge after STEMI.


Improved compliance with therapy is a strong rationale for timing the initiation of lipid-lowering drug therapy before discharge after STEMI. Longer-term lipid management after STEMI, including indications for targeting triglycerides and non high-density lipoprotein cholesterol, are addressed in the O Gara et al 2013 ACCF/AHA STEMI Guideline e391 AHA/ACC Secondary Prevention and Risk Reduction Ther- apy for Patients With Coronary and Other Vascular Disease: Although nitroglycerin can ameliorate symptoms and signs of myocardial ischemia by reducing LV preload and increas- ing coronary blood flow, it generally does not attenuate the myocardial injury associated with epicardial coronary artery occlusion unless vasospasm plays a significant role. Intrave- nous nitroglycerin may be useful to treat patients with STEMI and hypertension or HF. Nitrates should not be given to patients with hypotension, marked bradycardia or tachycardia, RV infarction, or 5'phosphodiesterase inhibitor use within the There is no role for the routine use of oral nitrates in the convalescent phase of STEMI. 8.5. Calcium Channel Blockers An overview of 28 RCTs involving 19000 patients demon- strated no beneficial effect on infarct size or the rate of rein- farction when calcium channel blocker therapy was initiated during either the acute or convalescent phase of STEMI.445 Calcium channel blockers may be useful, however, to relieve ischemia, lower BP, or control the ventricular response rate to atrial fibrillation (AF) in patients who are intolerant of beta blockers. Caution is advised in patients with LV systolic dys- function. The use of the immediate-release nifedipine is con- traindicated in patients with STEMI because of hypotension and reflex sympathetic activation with tachycardia.446 Few data exist to support or refute the value of the routine use of oxygen in the acute phase of STEMI, and more research is needed.


The use of the immediate-release nifedipine is con- traindicated in patients with STEMI because of hypotension and reflex sympathetic activation with tachycardia.446 Few data exist to support or refute the value of the routine use of oxygen in the acute phase of STEMI, and more research is needed. A pooled Cochrane analysis of 3 trials showed a 3-fold higher risk of death for patients with confirmed acute MI treated with oxygen than for patients with acute MI man- aged on room air. Oxygen therapy is appropriate for patients who are hypoxemic (oxygen saturation <90%) and may have a salutary placebo effect in others. Supplementary oxygen may, however, increase coronary vascular resistance.447 Oxy- gen should be administered with caution to patients with chronic obstructive pulmonary disease and carbon dioxide retention. 8.7. Analgesics: Morphine, Nonsteroidal Anti- Inflammatory Drugs, and Cyclooxygenase II Inhibitors In the absence of a history of hypersensitivity, morphine sulfate is the drug of choice for pain relief in patients with STEMI, especially those whose course is complicated by acute pulmonary edema. It can alleviate the work of breath- ing, reduce anxiety, and favorably affect ventricular loading conditions. The dose of morphine sulfate needed to achieve adequate pain control will vary depending on patient age, body size, BP, and heart rate. Naloxone can be administered in doses of 0.1 to 0.2 mg IV every 15 minutes when indicated to reverse the narcotic effects of morphine, and atropine 0.5 to 1.5 mg IV may be administered to counter excessive mor- phine-related bradycardia.


Naloxone can be administered in doses of 0.1 to 0.2 mg IV every 15 minutes when indicated to reverse the narcotic effects of morphine, and atropine 0.5 to 1.5 mg IV may be administered to counter excessive mor- phine-related bradycardia. Epidemiological studies and retrospective analyses of RCTs have suggested that nonsteroidal anti-inflammatory drugs and selective cyclooxygenase II enzyme (COX-2) inhibitors may be associated with an increased risk of death, reinfarction, car- diac rupture, hypertension, renal insufficiency, and HF.448 451 Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors are contraindicated in patients with STEMI. They should not be initiated in the acute phase and should be discontinued in patients using them before hospitalization. 9. Complications After STEMI 9.1. Cardiogenic Shock 9.1.1. Treatment of Cardiogenic Shock: Recommendations Class I 1. Emergency revascularization with either PCI or CABG is recommended in suitable patients with cardiogenic shock due to pump failure after STEMI irrespective of the time delay from MI onset.212,379,452 (Level of Evidence: B) 2. In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI and cardiogenic shock who are unsuitable candidates for either PCI or CABG.81,453,454 (Level of Evidence: B) Class IIa 1. The use of intra-aortic balloon pump (IABP) coun-ter- pulsation can be useful for patients with cardiogenic shock after STEMI who do not quickly stabilize with (Level of Evidence: B) Class IIb 1. Alternative LV assist devices for circulatory support may be considered in patients with refractory cardio- genic shock. (Level of Evidence: C) Cardiogenic shock in patients with STEMI may be caused by extensive LV infarction or by mechanical complications, including papillary muscle rupture, ventricular septal rup- ture, free-wall rupture with tamponade, and RV infarction. The onset of cardiogenic shock due to mechanical compli- cations after STEMI is bimodal; most cases occur within 24 hours.


The onset of cardiogenic shock due to mechanical compli- cations after STEMI is bimodal; most cases occur within 24 hours. For those with pump failure, 15% of cases occur at time of presentation, and 85% develop during hospitalization. Revascularization with timely PCI or CABG is the preferred reperfusion strategy for patients with STEMI and shock due to pump failure, irrespective of the time delay. Shock or severe HF is perhaps the only clinical scenario in which acute revascularization of significant stenoses in noninfarct arter- ies can be justified. In the SHOCK trial, mortality rates at 6 and 1 year were significantly lower in patients allocated to emergency revascularization than in patients who received immediate medical stabilization.212,354 Nearly two thirds of the patients in the medical stabilization group received fibrinolytic therapy, and 25% underwent delayed revasculariza- tion. IABP support was used in 86% of both groups. Although the trial did not show benefit with emergency revascularization for the prespecified age group >75 years, the small number of patients in the trial did not allow for firm conclusions to be drawn about management. Elderly patients offered emer- gency revascularization in the nonrandomized SHOCK regis- try had a substantial adjusted survival benefit with emergency revascularization compared with delayed or no revasculariza- Similar findings in favor of early revascularization for selected elderly patients were reported from 2 additional Although age alone is not a contraindication to emergency revascularization in this setting, individual judg- ment based on comorbidities, functional status, and patient directives is necessary in the elderly. Triage and immediate transfer to a PCI-capable facility with on-site cardiac surgi- cal backup are indicated for patients with STEMI complicated by shock.


Triage and immediate transfer to a PCI-capable facility with on-site cardiac surgi- cal backup are indicated for patients with STEMI complicated by shock. Fibrinolytic therapy is reserved for patients without contraindications within 24 hours of MI for whom revascu- larization is considered not feasible for technical, anatomic, or patient-related issues. The need for hemodynamic support with inotropic therapy, IABP, or both should be assessed on an individual basis. Observational data on the usefulness of IABP in this setting are conflicting. A meta-analysis supports IABP therapy as an adjunct to fibrinolysis but not to primary PCI.458 Compared with IABP, LV assist devices may provide superior hemodynamic support and serve as more effective bridges to recovery or transplantation, though experience with their use in this setting is limited.463,464 Medical support with inotropes and vasopressor agents should be individualized and guided by invasive hemodynamic monitoring. Use of dopamine in this setting may be associated with excess hazard.465 9.2. Severe HF The development of HF after STEMI is an indication for angiography with intent to proceed with revascularization if not previously performed. LV myocardium may be ischemic, stunned, hibernating, or irrevocably injured, and viability assessment may be needed depending on the timing of revas- cularization. Ischemic (functional) mitral regurgitation due to LV remodeling may coexist, progress over time, and require surgical attention depending on its severity. Medical treatment is based on the use of diuretics, vasodilators, and inotropic agents when required. Inhibitors of the renin-angiotensin- aldosterone system should be provided as tolerated, and the indications for beta-blocker therapy should be evaluated con- tinuously throughout the hospital course. 9.3.


Inhibitors of the renin-angiotensin- aldosterone system should be provided as tolerated, and the indications for beta-blocker therapy should be evaluated con- tinuously throughout the hospital course. 9.3. RV Infarction RV infarction complicates the course of approximately one third of patients with inferior STEMI, is most often due to proximal occlusion of the right coronary artery, and is asso- ciated with a higher mortality risk. Evidence of RV involve- ment should be sought in all patients with inferior STEMI. The clinical triad of hypotension, clear lung fields, and elevated jugular venous pressure is characteristic. Demon- stration of 1-mm ST elevation in lead V1 and in right pre- cordial lead V4 R is the most sensitive ECG marker of RV Transthoracic echocardiography can be helpful in patients with initially nondiagnostic findings.467 Treat- ment includes maintenance of RV preload, reduction of RV afterload, inotropic support if needed, and immediate reper- Nitrates and diuretics should be avoided. Restora- tion of atrioventricular (AV) synchrony or cardioversion from AF may be needed. 9.4. Mechanical Complications Mechanical complications after STEMI have a bimodal, tem- poral distribution: Most occur in the first 24 hours, and the remainder present within the first week. The presence of a new systolic murmur indicates the possibility of either ventricle septal rupture or mitral regurgitation. Diagnosis usually can be established with transthoracic echocardiography. Surgical con- sultation should be obtained when a mechanical defect is sus- pected. Prompt repair (with or without CABG) is indicated in most cases. IABP can provide temporary circulatory support. 9.4.2. Mitral Regurgitation Mitral regurgitation after STEMI occurs via 1 of 2 mecha- nisms: papillary muscle rupture or postinfarction LV remod- eling with displacement of the papillary muscles, leaflet tethering, and annular dilatation.


Mitral Regurgitation Mitral regurgitation after STEMI occurs via 1 of 2 mecha- nisms: papillary muscle rupture or postinfarction LV remod- eling with displacement of the papillary muscles, leaflet tethering, and annular dilatation. Acute rupture affects the posteromedial papillary muscle more often than anterolateral papillary muscle because of its singular blood supply.470,471 Acute severe mitral regurgitation is characterized by pulmo- nary edema and/or shock; a systolic murmur may not always be appreciated. Suitable patients with papillary muscle rup- ture should be considered for urgent surgery while temporary stabilization with medical therapy and IABP is attempted. Mitral valve replacement rather than repair usually is required in this setting. Although emergency mitral valve replacement is associated with a relatively high mortality rate (20%), sur- vival and ventricular function are improved with surgery com- pared with medical therapy alone. Delay to operation appears to increase the risk of further myocardial injury, organ failure, Five-year survival rates after surgery average With ischemic (functional) mitral regurgitation, treatment is focused on timely reperfusion, diuretics, and afterload reduction. The severity of mitral regurgitation may improve in some patients with aggressive medical treatment, PCI, or both. The rate of long-term survival after STEMI declines as a function of residual mitral regurgitation severity. If surgery is required during the index hospitalization because of ongoing ischemia or HF, mitral valve repair with a downsized annu- loplasty ring usually is performed, though valve replacement may be preferred in many cases. In this regard, management of ischemic mitral regurgitation differs importantly from that of myxomatous mitral regurgitation. 9.4.3. Ventricular Septal Rupture Ventricular septal rupture usually is heralded by a loud sys- tolic murmur and HF or shock, depending on the size of the defect and the degree of RV and LV dysfunction.