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Acute ST-elevation myocardial infarction: Antiplatelet therapy

Acute ST-elevation myocardial infarction: Antiplatelet therapy
Authors:
A Michael Lincoff, MD
Donald Cutlip, MD
Section Editors:
Freek Verheugt, MD, FACC, FESC
Christopher P Cannon, MD
Deputy Editor:
Todd F Dardas, MD, MS
Literature review current through: Jan 2024.
This topic last updated: Jun 08, 2023.

INTRODUCTION — This topic addresses the use of antiplatelet therapy in patients with acute ST-elevation myocardial infarction (STEMI) from presentation until discharge.

Other relevant topics include:

●(See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy".)

●(See "Acute ST-elevation myocardial infarction: Management of anticoagulation".)

●(See "Mechanisms of acute coronary syndromes related to atherosclerosis".)

●(See "Inherited platelet function disorders (IPFDs)", section on 'Conceptual framework'.)

●(See "The role of platelets in coronary heart disease".)

●(See "Overview of hemostasis", section on 'Platelet aggregation'.)

●(See "Platelet biology and mechanism of anti-platelet drugs", section on 'Platelet activation'.)

OUR APPROACH TO EARLY DAPT — Most patients with acute STEMI should be started on dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor blocker as soon as possible after the diagnosis is established. Administration may happen in the ambulance or emergency department.

The loading dose of uncoated aspirin is 162 to 325 mg. The first tablet should be chewed or crushed to establish a high blood level quickly. More rapid absorption occurs with nonenteric-coated formulations.

The choice of P2Y12 receptor blocker is determined in part by the reperfusion strategy chosen (see "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy"):

●For patients receiving primary percutaneous coronary intervention, we start either ticagrelor (180 mg loading dose) or prasugrel (60 mg loading dose) rather than clopidogrel (table 1).

●For patients receiving fibrinolysis, we give a loading dose of clopidogrel (300 mg in patients 75 years or younger or 75 mg in patients over 75 years of age).

●For the uncommon patient who will likely need early coronary artery bypass graft surgery, we do not give a P2Y12 receptor blocker.

●In patients who will not be reperfused, we start ticagrelor (180 mg loading dose).

For most STEMI patients, we do not give a glycoprotein IIb/IIIa inhibitor prior to coronary angiography in the catheterization laboratory. (See 'Intravenous agents' below.)

RATIONALE — Platelet adhesion and aggregation are early steps in the formation of occlusive coronary artery thrombus (see "The role of platelets in coronary heart disease"). Dual antiplatelet therapy (DAPT) is directed at limiting these early steps. Additional benefits are seen depending on the reperfusion strategy chosen:

●The benefit from fibrinolytic therapy is limited by the failure to achieve normal (Thrombosis in Myocardial Infarction [TIMI] grade 3) flow in 40 to 50 percent of infarct-related arteries. This is important because the restoration of normal flow is associated with improved outcomes. In addition, reocclusion occurs in 5 to 15 percent of cases. These observations provided support for the hypothesis that more aggressive (than aspirin alone) antiplatelet therapy might improve outcomes following fibrinolytic therapy. (See "Diagnosis and management of failed fibrinolysis or threatened reocclusion in acute ST-elevation myocardial infarction", section on 'Threatened reocclusion or reinfarction' and "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy", section on 'Concomitant therapies'.)

●In patients who undergo percutaneous coronary intervention with stenting, stent thrombosis is a potentially catastrophic complication. DAPT reduces the risk of stent thrombosis. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients".)

ASPIRIN FOR ALL PATIENTS — Aspirin has established efficacy and safety in the acute therapy of patients with STEMI, similar to all patients with coronary artery disease. (See "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease", section on 'Summary and recommendations'.)

The loading dose of 162 to 325 mg of uncoated aspirin should be given as soon as possible to any patient with STEMI, irrespective of treatment strategy [1]. The first tablet should be chewed or crushed to establish a high blood level quickly. More rapid absorption occurs with nonenteric-coated formulations. After the loading dose, we prescribe aspirin at a dose of 75 to 81 mg once daily rather than higher doses since there is no benefit from a higher dose, and there is a higher risk of bleeding, particularly from the gastrointestinal tract [2,3]. For patients taking ticagrelor (see 'P2Y12 use' below), aspirin must be given at a dose ≤100 mg once daily, based on results in the PLATO study [4] and as listed in the US Food and Drug Administration package insert for the drug.

For patients with a history of possible aspirin allergy, the optimal approach is not known. In patients who cannot be desensitized before the procedure, we administer a P2Y12 receptor blocker alone. Most experts prefer one of the more potent agents (eg, prasugrel or ticagrelor) to clopidogrel for those patients in whom clopidogrel would ordinarily be chosen. When the patient is stable, an evaluation for possible aspirin desensitization can be performed by an allergy expert. (See "Introduction of aspirin to patients with aspirin hypersensitivity requiring cardiovascular interventions", section on 'Indications for urgent aspirin therapy'.)

Aspirin therapy may be associated with gastrointestinal intolerance, including bleeding, allergy (primarily manifested as bronchospasm or asthma), or worsening of preexistent bleeding outside the gastrointestinal tract. Additional information regarding aspirin use is discussed separately. (See "Gastrointestinal bleeding in patients undergoing percutaneous coronary intervention" and "Introduction of aspirin to patients with aspirin hypersensitivity requiring cardiovascular interventions", section on 'Indications for urgent aspirin therapy'.)

PATIENTS RECEIVING FIBRINOLYTIC THERAPY — All patients treated with a fibrinolytic agent, including those for whom percutaneous coronary intervention (PCI) is planned following fibrinolysis, should receive a P2Y12 receptor blocker immediately on presentation (table 1) (see "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy"). We prefer clopidogrel as the initial P2Y12 receptor blocker rather than ticagrelor or prasugrel due to the increased risk of bleeding with the latter two. It should be kept in mind that pretreatment with ticagrelor or prasugrel is a relative contraindication to fibrinolytic therapy.

Two randomized trials of patients treated with fibrinolytic therapy showed clear evidence of angiographic and clinical mortality benefit without a significantly increased risk for major bleeding with the early administration of clopidogrel in patients also treated with aspirin [5,6]. We recommend a clopidogrel loading dose of 300 mg in patients age 75 years or younger receiving fibrinolysis (based on the safety experience in CLARITY-TIMI 28), but no loading dose (first dose 75 mg) in patients over 75 years of age [5].

For most patients treated with fibrinolytic therapy, we do not switch from clopidogrel to one of the more potent agents (eg, prasugrel and ticagrelor). However, for patients who undergo PCI more than 24 hours after fibrinolytic therapy, it is reasonable to switch to prasugrel or ticagrelor, particularly if PCI reveals high-risk features. Supportive evidence for this approach comes from the TRITON-TIMI 38 trial (discussed below), which compared prasugrel with clopidogrel and included approximately 2000 STEMI patients who underwent PCI after fibrinolysis (see 'Patients receiving primary PCI' below). Although the PLATO trial, comparing ticagrelor with clopidogrel, did not enroll patients who received fibrinolysis, we consider using either prasugrel or ticagrelor given the entire body of evidence that suggests the two are superior to clopidogrel in the setting of PCI after STEMI.

There is no evidence to support the use of a glycoprotein (GP) IIb/IIIa inhibitor acutely in patients receiving full-dose fibrinolytic therapy. In addition, we do not recommend the use of half-dose fibrinolytic therapy plus a GP IIb/IIIa inhibitor as a primary reperfusion strategy [7,8]. At a later PCI, it could be considered for complicated lesions. (See "Acute ST-elevation myocardial infarction: The use of fibrinolytic therapy".)

PATIENTS RECEIVING PRIMARY PCI — In addition to aspirin, all patients treated with primary percutaneous coronary intervention (PCI) should receive a P2Y12 receptor blocker as early as possible after the diagnosis is established (table 1). In most cases, we treat with prasugrel or ticagrelor rather than clopidogrel. The evidence supporting the use of P2Y12 receptor blocker in these patients comes from patients without STEMI undergoing PCI. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients".)

The choice between prasugrel and ticagrelor is made after taking into account factors such as local practice, familiarity, and cost. In choosing among the two, we also take into account patient factors such as age, weight, and history of prior stroke or transient ischemic attack.

Timing of initiation — We give a P2Y12 receptor blocker prior to diagnostic coronary angiography in almost all cases. Reasons to defer administration until after angiography include uncertainties of diagnosis or if administration would produce delays in transfer to PCI.

Strong evidence for an early benefit (such as a reduction in recurrent MI) from early initiation does not exist. Possible explanations include: In many patients, undergoing primary PCI reperfusion is established well in advance of the maximal antiplatelet effect of these drugs, there is significant patient-to-patient variability in the time it takes for a significant reduction, and there is difficulty in assessing an early benefit on ischemic events in patients with a very recent acute event [9-12]. Weak evidence supporting the very early use of P2Y12 receptor blockade comes from the ATLANTIC trial, which showed a significant reduction in early stent thrombosis, although there were no differences in ST-resolution or clinical outcomes [11].

Although early initiation of P2Y12 receptor blocker is recommended in STEMI patients with planned PCI, there is no evidence that achieving even earlier platelet inhibition using crushed tablets improves outcomes. The COMPARE CRUSH trial, which randomly assigned 727 individuals to either crushed or integral prasugrel tablets in the ambulance, found no significant difference in the primary outcome of the rate of TIMI 3 flow (table 2) in the infarct-related artery (31.0 versus 32.7 percent) at angiography [13]. In addition, there were no differences between the two groups in the rate of ischemic events at 30 days.

Selection of an oral agent — For patients undergoing primary PCI, we prefer either prasugrel or ticagrelor to clopidogrel based on the TRITON-TIMI 38 and PLATO trials of patients with STEMI and non-ST-elevation acute coronary syndromes (ACS) [4,14]. These two trials both concluded that ticagrelor or prasugrel was superior to clopidogrel for the primary composite endpoint and that there was no significant difference in the rate of major bleeding between the more potent P2Y12 receptor blocker and clopidogrel:

●Prasugrel was compared with clopidogrel in the TRITON-TIMI 38 trial of 13,608 moderate- to high-risk ACS patients undergoing PCI, including 3534 with STEMI [14]. STEMI patients included 2438 patients undergoing primary PCI and 1096 patients who had STEMI and were referred for PCI on average 38 hours post-MI. Patients intended for primary PCI were randomly assigned to either prasugrel or clopidogrel immediately after enrollment (unlike other patients in the trial for whom the coronary anatomy had to be known before randomization and study drug administration). Prasugrel was given with a loading dose of 60 mg and maintenance dose of 10 mg once daily while clopidogrel was given with a 300 mg loading dose. Among the 3534 patients with STEMI, the primary efficacy endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke occurred significantly less often in patients treated with prasugrel at 15-month follow-up (10 versus 12.4 percent; hazard ratio [HR] 0.79; 95% CI 0.65-0.97), driven primarily by a significant reduction in nonfatal MI (7.4 versus 9.7 percent) [15]. There were similar rates of non-CABG-related major bleeding between the two groups.

●Ticagrelor was compared with clopidogrel in over 18,000 ACS patients in the PLATO trial, 38 percent of whom had STEMI with intended PCI. Patients were randomly assigned to ticagrelor 180 mg loading dose followed by 90 mg twice daily or clopidogrel 300 mg loading dose followed by 75 mg once daily [4]. Among patients with STEMI, there was a trend toward a lower rate of the primary endpoint with ticagrelor at 12 months (9.4 versus 10.8 percent; HR 0.87, 95% CI 0.75-1.01) and similar rates of major bleeding [16]. In the main trial, rates of bleeding were similar between ticagrelor and clopidogrel [4].

Other aspects of these trials are discussed in detail elsewhere. (See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy".)

At least two randomized trials have directly compared prasugrel with ticagrelor:

●In the PRAGUE-18 study, 1230 ACS individuals (90 percent STEMI) were randomly assigned to prasugrel or ticagrelor before diagnostic angiography [17]. The study was stopped early for futility after about 50 percent enrollment. There was no significant difference in the rate of primary endpoint of death, reinfarction, urgent target vessel revascularization, stroke, or serious bleeding at 30 days (4 versus 4.1 percent, respectively) between prasugrel and ticagrelor.

●The ISAR-REACT 5 open-label trial randomly assigned 4018 patients with ACS (41 percent STEMI) and planned invasive evaluation to ticagrelor or prasugrel as soon as possible after randomization [18]. The primary endpoint (a composite of death, MI, or stroke at one year) occurred more often in patients who received ticagrelor (9.3 versus 6.9 percent, respectively; HR 1.36, 95% CI 1.09-1.70). Limitations of the trial compared with TRITON-TIMI 38 and PLATO include modest sample size open-label design and telephone follow-up in more than 90 percent of patients. In a prespecified analysis of the STEMI subgroup, there was no difference in the primary endpoint (10.1 versus 7.9 percent, respectively; HR 1.31, 95% CI 0.95-1.82) or bleeding. Recurrent MI was higher with ticagrelor (5.3 versus 2.8 percent; HR 1.95, 95% CI 1.18-3.23) [19].

The explanation for the lower risk of ischemic events with prasugrel compared with ticagrelor in the overall ISAR-REACT 5 trial is not understood. Additional studies are needed to see if this will be confirmed. Until further evidence is available to support or refute the superiority of prasugrel, we believe that either prasugrel or ticagrelor is a reasonable choice for patients with STEMI. (See 'P2Y12 use' below.)

Intravenous agents — Glycoprotein (GP) IIb/IIIa inhibitors and cangrelor are intravenous antiplatelet agents that are not routinely used in patients with STEMI.

Glycoprotein IIb/IIIa inhibitors — For patients undergoing primary PCI and who receive early antiplatelet therapy with aspirin and a P2Y12 inhibitor, we do not routinely give an intravenous GP IIb/IIIa inhibitor [20,21]. However, we consider administering one in patients who either have not received pretreatment with a P2Y12 receptor blocker or for whom the duration between P2Y12 inhibitor administration and PCI is short (<30 to 45 minutes). Other patients undergoing primary PCI who might benefit from a GP IIb/IIIa inhibitor include those who are found to have no or slow reflow, large thrombus burden, or intraprocedural bailout for distal embolization, coronary artery dissection, or hemodynamic instability.

Trials that compared GP IIb/IIIa inhibitors with placebo and that found evidence of benefit were performed before the routine use of potent P2Y12 inhibitors (eg, ticagrelor and prasugrel). There is some evidence supporting the use of abciximab in patients who are not pretreated with a P2Y12 inhibitor [7]. Evidence of benefit from either tirofiban or eptifibatide in this setting is less convincing [22-28].

More contemporary trials that routinely used P2Y12 inhibitor loading have not demonstrated benefit from the routine use of a GP IIb/IIIa inhibitor. The BRIGHT trial showed no benefit of adding GP inhibition to unfractionated heparin [29].

For those uncommon patients for whom the administration of a GP IIb/IIIa inhibitor at the time of primary PCI may be reasonable, we prefer the intravenous route. The intracoronary route has not been shown to be of value and is not licensed by the US Food and Drug Administration, European Medicines Agency (eptifibatide), or member European Union countries (abciximab or tirofiban) [30-34].

Randomized comparisons of major adverse cardiovascular outcomes using these agents have been performed. Available data from medium-sized randomized trials with surrogate endpoints and observational studies suggest equivalent efficacy among abciximab, tirofiban, and eptifibatide [8,25,26,35-42]. UpToDate's authors and reviewers choose high-dose tirofiban based on concerns about cost and availability. Of note, abciximab is no longer marketed in the United States, Canada, and most European countries.

The dosing regimens for abciximab, eptifibatide, and tirofiban for patients are based on dosing regimens used in clinical trials. The duration of therapy depends on the agent selected, and is 12 hours for abciximab and 18 to 24 hours for eptifibatide or tirofiban:

●Tirofiban – A loading dose of 25 mcg/kg (referred to as the high-bolus dose) over five minutes or less, which should be followed by a continuous infusion of 0.15 mcg/kg/min, which is continued for up to 18 hours [43]. This dose of tirofiban has shown benefit in small studies [44,45] but has not been validated in large clinical trials. We are concerned that any lower dose will not achieve adequate GP IIb/IIIa receptor blockade if given soon before PCI. The optimal dose for patients not undergoing PCI within four hours is unknown, but this dose may achieve adequate platelet inhibition [46-48].

If tirofiban is chosen, we suggest that the infusion dose be reduced by 50 percent in patients with an estimated creatinine clearance of <60 mL/min.

●Abciximab – A bolus of 0.25 mg/kg should be followed by a continuous infusion of 0.125 mcg/kg/min (maximum 10 mcg/min), which is continued for 12 hours. Abciximab is no longer available in most locations.

●Eptifibatide – A loading dose of 180 mcg/kg (maximum 22.6 mg) over one to two minutes should be followed by a continuous infusion of 2 mcg/kg/min (maximum 15 mg/hour), which is continued for 18 to 24 hours. A second 180 mcg/kg bolus should be given 10 minutes after the first bolus.

The continuous infusion should be reduced by 50 percent in patients with estimated creatinine clearance <50 mL/min.

Cangrelor — Cangrelor is an intravenous P2Y12 receptor blocker that has been compared with either clopidogrel or placebo in three randomized trials that included patients with STEMI and evaluated 48-hour outcomes [49-51]. This agent is sometimes used in STEMI patients in cardiogenic shock and/or when oral administration of a P2Y12 inhibitor is difficult. (See "Antithrombotic therapy for elective percutaneous coronary intervention: Clinical studies", section on 'Cangrelor'.)

Duration of dual antiplatelet therapy — Most STEMI patients treated with PCI are discharged from the hospital on DAPT (aspirin plus one of the following: clopidogrel 75 mg once daily; prasugrel 10 mg once daily; or ticagrelor 90 mg twice daily). We treat with DAPT for at least 12 months unless there has been a significant bleeding episode or there is a very high bleeding risk. In patients at high bleeding risk, ticagrelor monotherapy starting at about three months may be an option.

Extending the duration of DAPT — In patients who have received DAPT successfully for 12 months, we continue treatment for as long as an additional 36 months. This approach is based on the studies presented below, as well as some indirect evidence from trials in stable patients. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Duration and Type of Antiplatelet Treatment'.)

For those patients who will continue with ticagrelor (and aspirin) for longer than 12 months, we reduce the dose from 90 mg twice daily to 60 mg twice daily. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Treatment for longer than 12 months'.)

Evidence of benefit from longer DAPT comes from the DAPT and PEGASUS-TIMI 54 trials:

●The DAPT trial compared 18 months of DAPT (aspirin plus either clopidogrel or prasugrel) to aspirin alone in stented patients who had received DAPT for 12 months without major complication [52]. Approximately 10 percent of the nearly 10,000 patients had STEMI. The rates for each of the coprimary endpoints of stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death from any cause, MI, or stroke) were lower with continued P2Y12 therapy (0.4 versus 1.4 percent; HR 0.29, 95% CI 0.17-0.48 and 4.3 versus 5.9 percent; HR 0.71, 95% CI 0.59-0.85, respectively). However, the rate of the primary safety endpoint of moderate or severe bleeding, applying the GUSTO criteria (table 3), was increased with continued DAPT (2.5 versus 1.6 percent, p = 0.001). This trial is discussed in greater detail elsewhere. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Duration and Type of Antiplatelet Treatment'.)

●PEGASUS-TIMI 54 randomly assigned 21,162 patients with prior MI (53 percent STEMI) one to three years earlier (median time 1.7 years) to one of two doses of ticagrelor (90 or 60 mg twice daily) or placebo [53]. All patients continued aspirin. The primary efficacy endpoint (a composite of cardiovascular death, MI, or stroke) occurred less often with ticagrelor than with placebo at three years (7.85, 7.77, and 9.04 percent respectively; HRs 0.85, 95% CI 0.75-0.96 and 0.84, 95% CI 0.74-0.95). The rate of the primary safety endpoint of TIMI major bleeding (table 3) was higher in the ticagrelor 90 and 60 mg groups (2.6, 2.3, and 1.06 percent, respectively; p<0.001 for each dose versus placebo), but there was no difference in the rates of fatal and nonfatal intracranial hemorrhage (0.63, 0.71, and 0.60 percent, respectively).

Shortening the duration of DAPT — The following two trials compared 6 with 12 months of DAPT after PCI for ACS. There are significant limitations to the studies, including the use of clopidogrel in a significant number of patients. In addition, the small sample size of each is insufficient to show noninferiority for ischemic events. These two trials do not change our recommendation for treatment with at least 12 months of DAPT unless there has been a significant bleeding episode or there is a very high bleeding risk:

●The SMART-DATE trial attempted to assess the safety of a shorter duration of DAPT after ACS. In SMART-DATE, 2712 patients with ACS (about 38 percent STEMI) who underwent PCI were randomly assigned to 6 or 12 months or longer of DAPT with aspirin and a P2Y12 inhibitor (clopidogrel in 80 percent) [54]. The primary combined endpoint (all-cause death, MI, or stroke at 18 months) occurred at a similar rate in the two groups (4.7 and 4.2 percent, respectively; HR 1.13, 95% CI 0.79-1.62). The secondary endpoint of spontaneous MI occurred significantly more often in the six-month group (1.8 versus 0.8 percent; HR 2.41, 95% CI 1.15-5.05).

●The DAPT-STEMI trial randomly assigned 870 patients with STEMI who had undergone PCI with a zotarolimus-eluting stent and who were event free after six months of DAPT to aspirin or DAPT for an additional six months [55]. While there was no difference in a primary composite outcome, the small study size prevents any meaningful interpretation.

Dropping aspirin for long-term therapy — An alternative strategy for shortening the duration of DAPT is to drop aspirin and continue the P2Y12 agent. This approach has been studied in the GLOBAL LEADERS and TWILIGHT trials. This strategy is used in patients at high bleeding risk and is presented separately. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'DAPT versus P2Y12 receptor blocker monotherapy trials'.)

PATIENTS NOT REPERFUSED — We give P2Y12 receptor blocker therapy in addition to aspirin to patients with STEMI who are not reperfused. We prefer ticagrelor to clopidogrel; prasugrel has not been shown to be superior to clopidogrel in patients managed medically following acute coronary syndrome. We treat for one year based on the CURE and PLATO trials [56]. (See 'Selection of an oral agent' above and "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy", section on 'Our approach to early P2Y12 receptor blocker'.)

Our recommendation for the use of P2Y12 receptor blocker therapy is supported by the COMMIT/CCS-2 study, which demonstrated benefit from clopidogrel therapy compared with placebo at 28 days. In COMMIT/CCS, about half of the patients were not reperfused [6,57]. (See 'Patients receiving fibrinolytic therapy' above.)

Our preference for ticagrelor comes from the PLATO study in which outcomes were better with ticagrelor compared with clopidogrel in the subset of patients who did not undergo coronary revascularization. (See 'Patients receiving primary PCI' above.)

We do not recommend the use of glycoprotein IIb/III inhibitors in STEMI patients who do not receive reperfusion therapy:

●The TETAMI trial randomly assigned 1224 patients with an acute STEMI who did not undergo reperfusion to either tirofiban or placebo [58]. At 30 days, there was no significant difference in the combined endpoint of death, reinfarction, or recurrent angina (16.6 versus 16.4 percent, respectively). As discussed previously, patients participating in the PRISM trial (UA/NSTEMI) who were treated medically derived benefit from tirofiban if they were troponin positive.

POSSIBLE EARLY CABG — Most patients with an acute STEMI will be treated urgently with percutaneous coronary intervention (PCI) rather than coronary artery bypass graft surgery (CABG). However, an uncommon patient will need urgent CABG. Most of these will have received aspirin and a P2Y12 receptor blocker prior to diagnostic angiography as standard care (see 'Patients receiving primary PCI' above). For those uncommon patients who were not treated with a P2Y12 receptor blocker, some of our contributors might add an intravenous glycoprotein IIb/IIIa inhibitor if surgery will be delayed for more than a few hours.

Although we recommend stopping P2Y12 receptor blocker prior to CABG in most patients, any excess bleeding risk due to recent P2Y12 receptor blocker use in the minority of patients who will or might require early CABG must be weighed against the potentially deleterious effect of delaying or not administering such therapy [59]. In subgroup analysis of the CURE trial [60], patients with ACS who underwent CABG who received clopidogrel had a lower rate of adverse ischemic outcomes than those who did not. (See "Anticoagulant therapy in non-ST elevation acute coronary syndromes", section on 'Unfractionated heparin compared with bivalirudin'.)

In circumstances in which CABG might be known to be necessary (coronary anatomy known) or likely, and the cardiothoracic surgical team is uncomfortable operating on patients taking a P2Y12 receptor blocker, it is reasonable to defer giving these drugs until after angiography is performed. If PCI is decided on, a P2Y12 receptor blocker should be given. In patients treated with early CABG who do not receive an oral P2Y12 receptor blocker, the early initiation of a glycoprotein IIb/IIIa inhibitor or cangrelor may be useful. However, this strategy has not been formally evaluated. (See 'Patients receiving primary PCI' above.)

The risk of CABG-related bleeding in patients taking P2Y12 receptor blockers was evaluated in the following two studies:

●The likelihood of life-threatening or major bleeding within seven days of CABG was nonsignificantly increased in patients in the CURE trial who had received clopidogrel within the five days prior to CABG (9.6 versus 6.3 percent with placebo), but not in those who had discontinued clopidogrel ≥5 days prior to CABG (4.4 versus 5.3 percent) [60]. This finding is supported by several observational studies [61-65]. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Bleeding'.)

●In the TRITON-TIMI 38 [14] and PLATO [4] trials of P2Y12 receptor blocker therapy, the risk of CABG-related major bleeding was significantly increased with prasugrel (13.4 versus 3.2 percent) but not ticagrelor (7.4 versus 7.9 percent) compared with clopidogrel. (See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy".)

For those patients who can wait for surgery, discontinuation for approximately five days allows for the antiplatelet effect of the P2Y12 receptor blocker to wash out. (See "Management of cardiac risk for noncardiac surgery", section on 'Antiplatelet therapy'.)

P2Y12 USE

Dose — The following are dosing regimens for P2Y12 receptor blockers in STEMI patients (table 1). These regimens are identical to those used in the PLATO and TRITON-TIMI 38 trials. (See 'Selection of an oral agent' above.)

For prasugrel, we give a loading dose of 60 mg and a maintenance dose of 10 mg once daily in most patients. Reducing the maintenance dose to 5 mg once daily (and continuing aspirin) after one month can be considered in Asian patients as an option for reducing dual antiplatelet therapy intensity and decreasing bleeding risk. Our experts would also consider reducing the dose to 5 mg once daily in patients 75 years or older or who weigh less than 60 kg, as was evaluated in the TRILOGY trial. (See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy", section on 'Ischemia-guided management'.)

East Asian individuals are known to be at higher-than-average bleeding risk and a lower-than-average thrombotic risk. In the HOST-REDUCE-POLYTECH-ACS trial, 2338 east Asian patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) were randomly assigned to 5 or 10 mg of prasugrel daily after one month of 10 mg daily [66]. All patients received aspirin 100 mg daily from PCI until the end of the study. The following was found at one year:

●There was no difference between the two groups in the rate of all-cause death (10 versus 14 events, respectively; 0.9 versus 1.2 percent, hazard ratio [HR] 0.71, 95% CI 0.32-1.60) or nonfatal MI (7 versus 8 events, respectively; 0.6 versus 0.7 percent, HR 0.87, 95% CI 0.32-2.40).

●Although the risk of Bleeding Academic Research Consortium (BARC) bleeding grade ≥2 (table 4) was lower with the 5 mg dose (33 versus 67 events, respectively; 2.9 versus 5.9 percent, HR 0.48, 95% CI 0.32-0.73), there was no difference in the rate of BARC bleeding grade ≥3 (9 versus 8 events, respectively; p = 0.82).

For ticagrelor, we give a loading dose of 180 mg and a maintenance dose of 90 mg twice daily. For those patients who will be continued on ticagrelor after 12 months from the diagnosis, our contributors reduce the dose to 60 mg twice daily. Our recommendations for the loading dose of the P2Y12 receptor blockers in STEMI are summarized in a table (table 1).

We prefer a clopidogrel loading dose of 600 mg instead of 300 mg in STEMI patients undergoing primary PCI (table 1), based principally on evidence from the HORIZONS AMI and CURRENT-OASIS 7 trials [2,67,68]. These trials suggested a reduced risk of ischemic events and stent thrombosis with little or no excess bleeding risk in patients undergoing PCI treated with a loading dose of clopidogrel 600 mg compared with 300 mg. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients" and "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Primary percutaneous coronary intervention'.)

Patients receiving long-term clopidogrel — Our approach to patients taking clopidogrel at the time of presentation is discussed separately. (See "Antithrombotic therapy for elective percutaneous coronary intervention: General use", section on 'Patients already taking clopidogrel'.)

Switching from ticagrelor or prasugrel to clopidogrel — Either ticagrelor or prasugrel is preferred to clopidogrel as the initial P2Y12 receptor blocker in STEMI patients undergoing PCI (see 'Patients receiving primary PCI' above). However, as many as 10 percent or higher of patients may need to switch to clopidogrel prior to discharge, and there may be a need to do so in similar numbers of patients after discharge [9,69,70]. Common reasons include an increased bleeding risk, nonbleeding side effects, and cost.

Based on mechanism of action and pharmacokinetic data, we advocate the following approach for patients who need to be switched [69,71] (see "Platelet biology and mechanism of anti-platelet drugs", section on 'ADP receptors (P2Y1 and P2Y12)'):

●For patients who have been receiving ticagrelor, we give the first dose of clopidogrel 12 hours after the last dose of ticagrelor [9,72-74]. We give a 600 mg loading dose of clopidogrel to all such patients.

●For patients who have been receiving prasugrel for five days or less, some of our experts load with clopidogrel 300 mg 24 hours after the last dose of prasugrel, while others do not load.

●For patients who have received prasugrel for more than five days, we start clopidogrel 75 mg 24 hours after the last dose of prasugrel.

Switching to ticagrelor — Some patients, such as those who have received fibrinolysis (see 'Patients receiving fibrinolytic therapy' above), may need to be switched from clopidogrel to ticagrelor early after STEMI. Other patients may need to be switched from prasugrel to ticagrelor.

When switching from clopidogrel or prasugrel to ticagrelor after STEMI, we give ticagrelor 180 mg (loading dose) at any time within 24 hours after the last dose (of clopidogrel or prasugrel). We then give ticagrelor 90 mg twice daily beginning approximately 12 hours later [9,53,75,76].

Duration — We treat most STEMI patients, irrespective of the reperfusion strategy, with dual antiplatelet therapy for at least one year based on the CURE, TRITON–TIMI 38, and PLATO trials. (See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy", section on 'Duration' and 'Duration of dual antiplatelet therapy' above.)

Additional comments regarding duration in patients undergoing PCI are found above. (See 'Duration of dual antiplatelet therapy' above.)

Role of genetic testing — We do not perform routine testing for genotypes associated with clopidogrel hyporesponsiveness. This issue is discussed elsewhere. (See "Clopidogrel resistance and clopidogrel treatment failure".)

PATIENTS TAKING ORAL ANTICOAGULANTS — The use of oral anticoagulant therapy, as well as both aspirin and a P2Y12 receptor blocker, is necessary in some patients with STEMI, such as those with atrial fibrillation, left ventricular mural thrombus, prosthetic heart valves, or deep vein thrombosis. In such patients, the risk of bleeding complications is increased compared with oral anticoagulant or dual antiplatelet therapy alone. The approach to antithrombotic therapy in patients who are candidates for two or three antithrombotic agents is discussed separately. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Bleeding' and "Acute coronary syndrome: Oral anticoagulation in medically treated patients", section on 'Rivaroxaban'.)

RECOMMENDATIONS OF OTHERS — Our recommendations are generally consistent with those made in major society guidelines and focused updates [77-81].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: ST-elevation myocardial infarction (STEMI)".)

SUMMARY AND RECOMMENDATIONS

●All patients – In patients with acute ST-elevation myocardial infarction (STEMI), there is strong evidence to support the early initiation of dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 receptor blocker, irrespective of treatment strategy (eg, fibrinolysis, primary percutaneous coronary intervention [PCI], or medical therapy). There is a limited role for intravenous glycoprotein (GP) IIb/IIIa inhibitor therapy in patients with planned primary PCI, and no role in patients receiving fibrinolytic therapy or those not undergoing reperfusion. Recommendations for the use of antiplatelet therapy in patients with STEMI are as follows.

•For all STEMI patients, we recommend aspirin as soon as possible after presentation (Grade 1A). (See 'Aspirin for all patients' above.)

The first aspirin tablet should contain 162 to 325 mg and should be chewed. The recommended maintenance dose of aspirin is 75 to 81 mg/day; when ticagrelor is used, the dose must be less than 100 mg/day. (See 'Aspirin for all patients' above.)

•For those patients with a history of gastrointestinal bleeding, drugs that reduce the risk of recurrent bleeding (eg, proton pump inhibitors) should be given. (See "Gastrointestinal bleeding in patients undergoing percutaneous coronary intervention", section on 'Summary and recommendations'.)

•Most patients with acute STEMI should be started on a P2Y12 receptor blocker in addition to aspirin as soon as possible after the diagnosis is established. The choice of P2Y12 receptor blocker is determined in part by the reperfusion strategy chosen. (See 'Our approach to early DAPT' above.)

●Fibrinolytic therapy

•For all STEMI patients who will be treated with fibrinolytic therapy, we start clopidogrel as soon as possible. For those who are less than 75 years of age, the suggested loading dose of clopidogrel is 300 mg. For patients 75 years of age or older, a loading dose of 75 mg should be given (table 1).

For patients treated with PCI more than 24 hours after fibrinolytic therapy, we suggest switching from clopidogrel to prasugrel or ticagrelor (Grade 2C). (See 'Patients receiving fibrinolytic therapy' above.)

All patients are treated for 12 months with DAPT. (See 'Duration of dual antiplatelet therapy' above.)

●Primary percutaneous coronary intervention

•For patients with planned primary PCI, we suggest ticagrelor or prasugrel in preference to clopidogrel (Grade 2B). The loading dose for ticagrelor is 180 mg and for prasugrel is 60 mg (table 1). (See 'Patients receiving primary PCI' above.)

For those patients in whom clopidogrel is chosen, we recommend a loading dose of 600 mg rather than any other dose (Grade 1B). We then start 75 mg once daily.

For patients not at high bleeding risk and who do not have planned noncardiac surgery within one year, we treat with DAPT for at least 12 months. (See 'Duration' above.)

•For most patients undergoing primary PCI and who receive early antiplatelet therapy with aspirin and a P2Y12 inhibitor, we recommend not routinely using a GP IIb/IIIa inhibitor (Grade 1B). (See 'Intravenous agents' above.)

For patients who do not receive a P2Y12 receptor blocker prior to PCI or for whom the duration between P2Y12 inhibitor administration and PCI is short (<30 to 45 minutes), we suggest the addition of a GP IIb/IIIa inhibitor or cangrelor, as opposed to not adding one of these agents, after diagnostic angiography (Grade 2C). This is particularly true for patients with large thrombus burden and low bleeding risk.

UpToDate's authors and reviewers generally prefer tirofiban if a GP IIb/IIIa inhibitor is used. (See 'Intravenous agents' above.)

●No reperfusion therapy – For patients receiving neither fibrinolytic therapy nor primary PCI, we suggest ticagrelor in preference to clopidogrel or prasugrel (Grade 2C). (See 'Patients not reperfused' above.)

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Topic 94 Version 102.0

References

1 : Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.

2 : Dose comparisons of clopidogrel and aspirin in acute coronary syndromes.

3 : Association of Discharge Aspirin Dose With Outcomes After Acute Myocardial Infarction: Insights From the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study.

4 : Ticagrelor versus clopidogrel in patients with acute coronary syndromes.

5 : Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.

6 : Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.

7 : Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

8 : Acute ST-segment elevation myocardial infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

9 : Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study.

10 : Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study.

11 : Prehospital ticagrelor in ST-segment elevation myocardial infarction.

12 : Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

13 : Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial.

14 : Prasugrel versus clopidogrel in patients with acute coronary syndromes.

15 : Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial.

16 : Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis.

17 : Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study.

18 : Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

19 : Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

20 : Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials.

21 : Facilitated PCI in patients with ST-elevation myocardial infarction.

22 : Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial.

23 : Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial.

24 : Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction.

25 : Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

26 : Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome.

27 : Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes.

28 : Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT Investigators.

29 : Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial.

30 : Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial.

31 : Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial.

32 : Meta-analysis of prospective randomized controlled trials comparing intracoronary versus intravenous abciximab in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

33 : Meta-analysis of randomized controlled trials comparing intracoronary and intravenous administration of glycoprotein IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction.

34 : Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial.

35 : Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial.

36 : Eptifibatide vs abciximab as adjunctive therapy during primary percutaneous coronary intervention for acute myocardial infarction.

37 : Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial.

38 : The relative safety and efficacy of abciximab and eptifibatide in patients undergoing primary percutaneous coronary intervention: insights from a large regional registry of contemporary percutaneous coronary intervention.

39 : Benefits from small molecule administration as compared with abciximab among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-analysis.

40 : Randomized comparison of eptifibatide versus abciximab in primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: results of the EVA-AMI Trial.

41 : Eptifibatide is noninferior to abciximab in primary percutaneous coronary intervention: results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry).

42 : Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse) trial.

43 : Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugrel administration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse) trial.

44 : Defining the role of platelet glycoprotein receptor inhibitors in STEMI: focus on tirofiban.

45 : Enhanced early inhibition of platelet aggregation with an increased bolus of tirofiban.

46 : A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina.

47 : Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction.

48 : Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial.

49 : Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial.

50 : Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial.

51 : Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

52 : Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.

53 : Long-term use of ticagrelor in patients with prior myocardial infarction.

54 : 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial.

55 : Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial.

56 : Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.

57 : Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.

58 : The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial.

59 : Is clopidogrel cardiovascular medicine's double-edged sword?

60 : Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial.

61 : Does clopidogrel increase blood loss following coronary artery bypass surgery?

62 : The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting.

63 : Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery.

64 : Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery: a multicenter analysis.

65 : Clopidogrel use and bleeding after coronary artery bypass graft surgery.

66 : Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial.

67 : Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial.

68 : Role of clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: results from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial.

69 : Switching P2Y12-receptor inhibitors in patients with coronary artery disease.

70 : In-hospital switching between adenosine diphosphate receptor inhibitors in patients with acute myocardial infarction treated with percutaneous coronary intervention: Insights into contemporary practice from the TRANSLATE-ACS study.

71 : Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial.

72 : Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study.

73 : A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study.

74 : Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial.

75 : International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies.

76 : Pharmacodynamic Effects of Switching From Prasugrel to Ticagrelor: Results of the Prospective, Randomized SWAP-3 Study.

77 : Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

78 : 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

79 : 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.

80 : ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation.

81 : 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

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