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. 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 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. 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. 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. 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. 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. 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. 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. 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. 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. 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). (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. (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 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. 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. 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. 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. (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. 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. 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. 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. 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). 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. 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. (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. 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. 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. 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. 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. 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. 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. 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. Data from the GUSTO-1 (The Global Use of Strategies to Open Occluded Coronary Arteries) trial and the SHOCK registry O Gara et al 2013 ACCF/AHA STEMI Guideline e393 indicate that ventricular septal rupture occurs most often within the first 24 hours in patients with STEMI treated with Emergency surgical repair is neces- sary, even in hemodynamically stable patients,479 481 because the rupture site can expand abruptly, resulting in sudden hemo- dynamic collapse in previously stable patients.481 Temporiz- ing medical treatment consists of inotropic and vasodilator agents, with IABP when needed. The surgical mortality rate remains high, especially among patients with shock, ranging Mortality risk is higher for patients with inferior-basal defects than for those with anterior-apical defects. Percutaneous closure is a less invasive option that might allow for initial hemodynamic stabilization, but experience with this approach is limited, and residual shunts are common. Further technical developments and prospective trials are required to identify patients best suited for transcatheter closure. 9.4.4. LV Free-Wall Rupture Free-wall rupture is characterized by recurrent chest pain and ST-T-wave changes, with rapid progression to hemodynamic collapse, electromechanical dissociation, and death.484 It is observed most frequently in patients with first MI, anterior infarction, the elderly, and women. Other risk factors include hypertension during the acute phase of STEMI, lack of ante- cedent angina or prior MI, absence of collateral blood flow, Q waves on ECG, use of corticosteroids or nonsteroidal anti-inflammatory drugs, and administration of fibrinolytic therapy >14 hours after symptom onset.485,486 Pseudoaneu- rysm formation with contained rupture and tamponade can be recognized with transthoracic echocardiography, and emergency surgery should be considered. Most case series of patients reaching the operating room for management of this complication are of small size, with mortality rates 9.4.5. LV Aneurysm Ventricular aneurysm formation after STEMI occurs in <5% of patients and is more frequent in those with anterior infarc- tion. Incidence rates have declined with timely reperfusion. Surgery for LV aneurysm after STEMI is rarely needed but may be considered for treatment of HF, ventricular arrhyth- mias not amenable to drugs or radiofrequency ablation, or recurrent thromboembolism despite appropriate anticoagulant therapy. 9.5. Electrical Complications During the Hospital Phase of STEMI 9.5.1. Ventricular Arrhythmias Ventricular arrhythmias are common early after onset of STEMI, and not all require intervention. Out-of-hospital cardiac arrest with STEMI is most often due to lethal ven- tricular arrhythmias, including sustained VT and VF (Sec- tion 3.6.1). The mechanisms for these arrhythmias are multifactorial and include ongoing ischemia, hemodynamic and electrolyte abnormalities, reentry, and enhanced auto- maticity. As many as 10% of hospitalized patients receiv- ing fibrinolytic therapy in the GUSTO-I trial had sustained VT/VF complicating their course.488 An analysis of patients referred for primary PCI in the APEX-AMI (Assessment of Pexelizumab in Acute Myocardial Infarction) trial reported a lower incidence of sustained VT/VF (5.7%); 90% of cases occurred within 48 hours of presentation.489 Compared with patients without VT/VF, 90-day mortality risk was 2-fold higher for patients with early VT/VF (ie, before the comple- tion of primary PCI) and 5-fold higher for patients with late VT/VF (ie, after primary PCI). Several factors were asso- ciated with the occurrence of both early and late VT/VF, including HF, hypotension, tachycardia, shock, and TIMI flow grade. Treatment consists of immediate defibrillation or cardioversion for VF or pulseless sustained VT, respectively, and antiarrhythmic drug therapy in accordance with the 2010 Advanced Cardiac Life Support guidelines for sustained VT with a pulse.490 Prevention of VT/VF is directed to correction of electrolyte and acid/base abnormalities, optimization of myocardial perfusion, eradication of ongoing ischemia, and treatment of associated complications such as HF or shock. Early (within 24 hours of presentation) administration of beta blockers has been associated with a reduction in the incidence and is recommended for all patients without con- traindications (Section 8.1). The prophylactic use of lidocaine is not recommended. Premature ventricular complexes, non- sustained VT not associated with hemodynamic compromise, and accelerated idioventricular rhythms that emerge after reperfusion are not indicative of increased SCD risk and do not require specific therapy in the acute phase of STEMI. 9.5.2. Implantable Cardioverter-Defibrillator Therapy Before Discharge Class I 1. Implantable cardioverter-defibrillator (ICD) therapy is indicated before discharge in patients who develop sustained VT/VF more than 48 hours after STEMI, provided the arrhythmia is not due to transient or reversible ischemia, reinfarction, or metabolic ab- (Level of Evidence: B) Life-threatening ventricular arrhythmias that occur >48 hours after STEMI usually are associated with signifi- cant LV systolic dysfunction and signify poor prognosis. Although previous RCTs492,494,495 have not specifically addressed this population of patients with STEMI, they have shown clear and consistent benefit of ICD therapy for survivors of sustained VT or VF arrest.493 In the absence of a reversible cause, late (>48 hours) in-hospital sustained VT/VF is an indication for ICD therapy for secondary prevention of SCD. For other at-risk patients, particularly those with significantly reduced left ventricular ejection fraction (LVEF), candidacy for ICD therapy for primary prevention of SCD should be reassessed at 40 days after discharge (Section 10.3). See the 2008 ACCF/AHA/HRS Guidelines for Device-Based Therapy of Cardiac Rhythm 9.5.3. AF and Other Supraventricular Tachyarrhythmias AF, atrial flutter, and other supraventricular tachyarrhythmias occur frequently in patients with STEMI and are triggered by excessive sympathetic stimulation, atrial stretch due to LV or RV volume/pressure overload, atrial infarction, pericarditis, electrolyte abnormalities, hypoxia, or underlying lung dis- ease. By far the most common supraventricular arrhythmia is AF, which occurs in 8% to 22% of patients with STEMI, with higher rates in elderly patients and those with HF and hyper- tension. In a contemporary study, the incidence of new-onset AF during hospitalization was 6.3%.497 New-onset AF was significantly associated with shock, HF, stroke, and 90-day These observations mirrored those seen in earlier The cumulative incidence of AF among MI survivors with EF 0.40 over approximately 2 years of follow-up approaches 30%.500 Management of AF during hospitalization for STEMI is based on the usual considerations of rhythm versus rate con- trol and the indications for anticoagulation according to cur- For hemodynamically unstable patients or those with ongoing ischemic symptoms, treatment should be implemented according to the 2010 Advanced Cardiac Life Support guideline for management of unstable supra- If medical treatment is unsuccessful, synchronized, direct current cardioversion may be indicated. Provision of anticoagulation in the context of DAPT creates additional challenges related to the risk of bleeding (Section 9.7). 9.5.4. Bradycardia, AV Block, and Intraventricular Conduction Defects 9.5.4.1. Pacing in STEMI: Recommendation Class I 1. Temporary pacing is indicated for symptomatic bradyarrhythmias unresponsive to medical treat- ment. (Level of Evidence: C) Sinus bradycardia is common early after STEMI, particularly with inferior location. It is mediated through increased vagal tone, is usually self-limited, and gener- ally requires no treatment. It may be necessary to withhold beta blockers until the bradycardia resolves. Symptom- atic or hemodynamically important sinus bradycardia should be treated with atropine or temporary pacing if not The development of AV block and intraventricular conduc- tion delays is associated with the extent of infarction. The incidence of abnormal conduction has decreased substantially in the reperfusion era. In a survey of nearly 3 million hospi- tal discharges after MI from 1996 to 2003, the incidence of complete heart block was 3.7% in inferior/posterior MI and AV block of varying degree and persistent bundle-branch block develop in approximately 7% and 5% of patients with STEMI, respectively.506,507 High- grade (ie, second- or third-degree) AV block and persistent bundle-branch block are independently associated with worse short- and long-term prognosis in both inferior/posterior and anterior/lateral MI but are more ominous in anterior/lat- eral MI because of a relatively greater extent of myocardial First-degree AV block does not require treatment. High- grade AV block with inferior/posterior STEMI usually is transient and associated with a narrow complex/junc- tional escape rhythm that can be managed conservatively. Application of transcutaneous pacing pads for potential use is reasonable. Prophylactic placement of a temporary pac- ing system is recommended for high-grade AV block and/ or new bundle-branch (especially LBBB) or bifascicular block in patients with anterior/lateral MI. Choice of pacing system (transcutaneous versus transvenous) varies across institutions. Indications for permanent pacing for persis- tent AV block or bundle-branch block after STEMI are reviewed in the 2008 ACC/AHA/HRS device-based therapy 9.6.1. Management of Pericarditis After STEMI: Recommendations Class I 1. Aspirin is recommended for treatment of pericarditis (Level of Evidence: B) Class IIb 1. Administration of acetaminophen, colchicine, or narcotic analgesics may be reasonable if aspirin, even in higher doses, is not effective. (Level of Evidence: C) Class III: Harm 1. Glucocorticoids and nonsteroidal anti-inflammatory drugs are potentially harmful for treatment of peri- carditis after STEMI.510,511 (Level of Evidence: B) The incidence of acute pericarditis after STEMI has decreased with the aggressive use of reperfusion ther- Pericarditis should be considered in the differential diagnosis of recurrent chest pain after STEMI, particularly when the discomfort is pleuritic or posi- tional, radiates to the trapezius ridge, and is associated with a pericardial friction rub. Recurrent or worsening ST elevation without early T-wave inversion may be present. Distinction from reinfarction or acute stent thrombosis is crucial. In rare circumstances, if pain is persistent (>1 week) and accompa- nied by systemic features of malaise, fever, and increased inflammatory biomarkers, Dressler syndrome should be con- sidered. In most cases, the pain is self-limited and responds to conservative measures. The use of colchicine has been extrap- olated from its efficacy in other settings. Although pericarditis is not an absolute contraindication to anticoagulation,514 cau- tion should be exercised because of the potential for hemor- Asymptomatic pericardial effusions are common after It is important to exclude free-wall rupture when a pericardial effusion is present,518,519 especially if the O Gara et al 2013 ACCF/AHA STEMI Guideline e395 Whentamponadeispresent,free- wall rupture, hemorrhagic conversion, or aortic dissection should be considered.Anticoagulation should be discontinued in the pres- ence of a significant ( 1 cm) or enlarging pericardial effusion. 9.7. Thromboembolic and Bleeding Complications 9.7.1. Thromboembolic Complications 9.7.1.1. Anticoagulation: Recommendations Class I 1. Anticoagulant therapy with a vitamin K antagonist should be provided to patients with STEMI and AF with CHADS2 score# greater than or equal to 2, me- chanical heart valves, venous thromboembolism, or hypercoagulable disorder. (Level of Evidence: C) 2. The duration of triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor should be minimized to the extent possible to limit the risk of bleeding.** (Level of Evidence: C) Class IIa 1. Anticoagulant therapy with a vitamin K antagonist is reasonable for patients with STEMI and asymptom- atic LV mural thrombi. (Level of Evidence: C) Class IIb 1. Anticoagulant therapy may be considered for pa- tients with STEMI and anterior apical akinesis or dyskinesis. (Level of Evidence: C) 2. Targeting vitamin K antagonist therapy to a lower international normalized ratio (eg, 2.0 to 2.5) might be considered in patients with STEMI who are re- ceiving DAPT. (Level of Evidence: C) Previous recommendations for the use of vitamin K antagonists, either alone or in combination with low-dose aspirin, for second- ary prevention or for reducing the risk of systemic thromboem- bolism after STEMI, must be reconsidered in the era of DAPT.4,48 The availability of several P2Y12 receptor inhibitors has virtually eliminated the former reliance on vitamin K antagonists as an alternative to aspirin for aspirin-allergic patients. A meta-analy- sis of RCTs comparing warfarin plus aspirin to aspirin alone in patients with ACS showed that in studies with an international normalized ratio goal of 2.0 to 3.0, combination therapy was associated with a significant reduction in major adverse events at the expense of an increased risk of major bleeding.521 None of the trials included patients treated with primary PCI or DAPT. Triple therapy with a vitamin K antagonist, aspirin, and a receptor inhibitor should be restricted to specific clini- cal situations after STEMI in which the risk of systemic or venous thromboembolism or stent thrombosis is considered to exceed that of bleeding. Patient preferences and values should be taken into consideration, because individuals may weigh these outcomes differently. The novel oral anticoagulants such as dabigatran have not been evaluated in this context, and thus no recommendation for their use can be made. The duration of vitamin K antagonist therapy can be limited to 3 months in patients with or at risk for LV thrombus (eg, those with antero- apical akinesis or dyskinesis), whereas the duration of DAPT could be predicated on stent type or whether STEMI treatment included a stent.219,522,523 For patients undergoing primary PCI who require anticoagulation, avoidance of a DES is strongly preferred. When triple therapy is used, an international nor- malized ratio targeted to a range of 2.0 to 2.5 might be rea- sonable, though prospective data are lacking. 