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Acute ST-elevation myocardial infarction: Initial antiplatelet therapy

Acute ST-elevation myocardial infarction: Initial 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: Apr 2025. | This topic last updated: May 08, 2025.

INTRODUCTION — 

This topic addresses the use of antiplatelet therapy in patients with acute ST-elevation myocardial infarction (STEMI) from presentation until discharge. Based on the choice of reperfusion strategy (eg, percutaneous coronary intervention, fibrinolysis) (algorithm 1), appropriate antiplatelet and anticoagulant (algorithm 2) therapies are administered to reduce the risk of clot propagation and recurrent myocardial infarction (MI).

Other relevant topics for the acute management of patients with STEMI include:

●(See "Overview of the acute management of ST-elevation myocardial infarction".)

●(See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction".)

●(See "Acute ST-elevation myocardial infarction: Selecting a reperfusion strategy".)

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

ASPIRIN

Initial therapy — In patients with suspected or confirmed STEMI, we recommend aspirin therapy (algorithm 3). The loading dose is uncoated aspirin 162 to 325 mg, which should be provided as soon as possible and irrespective of the reperfusion strategy [1]. To promote rapid absorption and effect, the first tablet should be chewed or crushed.

This approach is consistent with North American and European guidelines [2-4].

Aspirin reduces the risk of mortality in patients with MI. The efficacy of aspirin in patients with acute coronary syndrome (ACS) was established in the ISIS-2 trial, in which patients with acute MI (54 percent with STEMI) who were treated with aspirin had a lower five-week rate of cardiovascular mortality compared with placebo (9.4 versus 12 percent; p<0.00001) [1]. The risk of bleeding was similar between groups (0.4 percent). The ISIS-trial was conducted before the use of percutaneous coronary intervention and other modern approaches (eg, P2Y12 inhibitors) to acute MI management.

Therapy upon discharge — The approach to aspirin therapy at discharge depends on the type of P2Y12 inhibitor chosen and the need for anticoagulation:

●P2Y12 therapy and no anticoagulation – After the initial aspirin dose, we prescribe aspirin 75 to 100 mg once daily rather than higher doses; there is no benefit from a higher dose, and higher doses increase the likelihood of bleeding from the gastrointestinal tract. In a trial that included 25,086 patients with ACS, patients randomized to receive aspirin 300 to 325 mg or aspirin 75 to 100 mg had similar rates of major bleeding (2.3 percent) [5]. In a substudy of 10,213 patients enrolled in a randomized trial, patients who received a higher dose of aspirin at discharge had higher rates of minor bleeding events (21.4 versus 19.5 percent; adjusted odds ratio 1.19, 95% CI 1.05-1.34) [6].

There is controversy concerning the dose of aspirin and the efficacy of ticagrelor, which led to US Food and Drug Administration (FDA) labeling that requires the use of low-dose aspirin in patients treated with ticagrelor [7-9].

●P2Y12 therapy in patients who require long-term anticoagulation – In patients who have an indication for long-term anticoagulation (eg, atrial fibrillation, mechanical mitral valve), the approach to therapy is discussed separately. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Our approach'.)

Aspirin therapy may be associated with gastrointestinal intolerance (eg, bleeding), worsening of preexistent bleeding outside the gastrointestinal tract, or allergy (primarily manifested as bronchospasm or asthma). 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'.)

INITIAL P2Y12 INHIBITOR BY REPERFUSION STRATEGY

Primary PCI — In patients with STEMI who undergo primary percutaneous coronary intervention (PCI) (algorithm 1), we recommend treatment with aspirin and a P2Y12 inhibitor rather than other antiplatelet regimens (algorithm 3). We suggest treatment with prasugrel or ticagrelor rather than clopidogrel. In patients ≥75 years old, history of stroke or transient ischemic attack (TIA), or weight <60 kg, we suggest ticagrelor rather than prasugrel due to a possible increase in the risk of bleeding with prasugrel in this population of patients.

In patients with STEMI, we give the P2Y12 receptor blocker prior to diagnostic coronary angiography whenever possible. Reasons to defer administration until after angiography include uncertainty of diagnosis or if the administration would lead to delays in transfer for PCI. In patients who did not receive oral P2Y12 therapy prior to diagnostic angiography, other reasonable options include initiation of therapy (ie, oral or intravenous P2Y12 inhibitor) prior to PCI or initiation of therapy immediately after PCI. (See 'Inability to administer an oral P2Y12 inhibitor' below.)

The following are dosing regimens for P2Y12 receptor blocker use in STEMI patients. These regimens are identical to those used in the PLATO and TRITON-TIMI 38 trials.

●Prasugrel – For prasugrel, we give a loading dose of 60 mg and a maintenance dose of 10 mg once daily beginning approximately 24 hours after the loading dose [10].

●Ticagrelor – For ticagrelor, we give a loading dose of 180 mg and a maintenance dose of 90 mg twice daily beginning approximately 12 hours after the loading dose [7]. For those patients who will be continued on ticagrelor after 12 months from the diagnosis, we reduce the dose to 60 mg twice daily.

●Clopidogrel – We prefer a clopidogrel loading dose of 600 mg instead of 300 mg in STEMI patients undergoing primary PCI, based principally on evidence from the HORIZONS AMI and CURRENT-OASIS 7 trials [5,11,12]. 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.

The maintenance dose of clopidogrel is 75 mg daily and should begin approximately 24 hours after the loading dose.

This approach is consistent with professional guidelines [2-4].

The recommendation for the use of dual antiplatelet therapy (DAPT) with PCI is based on a series of trials that found a lower risk of recurrent MI within 30 days of stenting with ticlopidine, a P2Y12 inhibitor similar to clopidogrel [13-16]. In a meta-analysis that included four trials that compared DAPT (ie, aspirin plus ticlopidine) with other strategies (ie, aspirin plus anticoagulation, aspirin monotherapy), patients who received aspirin plus ticlopidine had a lower rate of recurrent MI (relative risk [RR] 0.5, 95% CI 0.29-0.83) and a nonsignificant decrease in the rate of stent thrombosis (RR 0.26, 95% CI 0.06-1.14) compared with anticoagulation [17]. In the only trial that compared aspirin monotherapy with DAPT after PCI, patients who underwent PCI were randomized to one of three antithrombotic regimens, and patients randomly assigned to treatment with aspirin and ticlopidine had the lowest rate of recurrent MI compared with patients assigned to aspirin monotherapy or to aspirin plus anticoagulation (0.5 versus 3.1 and 2.5 percent) [14]. The rate of events that suggest stent complications within 30 days was lower with aspirin plus ticlopidine compared with aspirin alone (RR 0.15, 95% CI 0.05-0.43). Ticlopidine is no longer available for use and was replaced by clopidogrel, which has similar efficacy and is better tolerated (eg, lower risk of neutropenia) [18].

Trials that evaluated the efficacy and safety of P2Y12 inhibitors after stenting and that included patients with non-ST-elevation MI and STEMI found that prasugrel and ticagrelor likely have better efficacy than clopidogrel. Prasugrel and ticagrelor likely have similar efficacy, but the bleeding risk with prasugrel is probably higher than ticagrelor in patients at high risk of bleeding based on subgroup analyses:

●The ISAR-REACT 5 trial included 4018 patients with acute coronary syndrome (ACS; 41 percent STEMI) and planned invasive evaluation who were assigned to ticagrelor or prasugrel as soon as possible after randomization [19]. Patients with a history of stroke were excluded from this trial. The rate of recurrent MI was higher with ticagrelor (5.2 versus 2.7 percent; hazard ratio [HR] 2.1, 95% CI 1.2-3.5), while mortality was similar between groups (4.2 versus 4.5 percent; HR 1.1, 95% CI 0.68-1.74). In a prespecified analysis of patients with STEMI, the rate of recurrent MI was also higher with ticagrelor (5.3 versus 2.8 percent; HR 1.95, 95% CI 1.18-3.23) [20]. The rates of bleeding were similar (5.4 versus 4.8 percent in the prasugrel group).

●In the PRAGUE-18 study, 1230 patients with ACS (90 percent STEMI) were randomly assigned to prasugrel or ticagrelor before diagnostic angiography [21]. This trial excluded patients with history of stroke, age >75 years, and weight <60 kg. The study was stopped early for futility after approximately 50 percent of planned enrollment. There was no significant difference in the rate of the 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.

●Ticagrelor was compared with clopidogrel in over 18,000 ACS patients in the PLATO trial in which 38 percent of patients had STEMI with intent to manage with primary PCI [7]. 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. In the overall trial, rates of 12-month mortality (4.5 versus 5.9 percent; HR 0.78, 95% CI 0.69-0.89) and recurrent MI (5.8 versus 6.9 percent; HR 0.84, 95% CI 0.75-0.95) were lower with ticagrelor compared with clopidogrel. Rates of major bleeding were similar in patients treated with ticagrelor or clopidogrel (11.6 versus 11.2 percent), but there were conflicting rates of specific types of bleeding (eg, fatal bleeding rates were similar, fatal intracranial bleeding and non-coronary artery bypass graft surgery-related major bleeding rates were increased with ticagrelor). Further analysis did not identify risk factors for bleeding [22]. The rate of dyspnea was higher with ticagrelor (12.6 versus 8.4 percent).

Among patients with STEMI, the rate of mortality was nonsignificantly lower with ticagrelor (5 versus 6.1 percent; HR 0.82, 95% CI 0.67-1.00), while the rate of recurrent MI was lower with ticagrelor (4.7 versus 5.8 percent; HR 0.8, 95% CI 0.65-0.98) [23].

●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 [10]. Patients intended for primary PCI were randomly assigned to either prasugrel or clopidogrel immediately after enrollment. Prasugrel was given with a loading dose of 60 mg and a maintenance dose of 10 mg once daily while clopidogrel was given with a 300 mg loading dose. After 15 months of follow-up, the rates of all-cause death were similar (3.0 versus 3.2 percent in the clopidogrel group; HR 0.95, 95% CI 0.78-1.16), and the rate of recurrent MI was lower with prasugrel (7.3 versus 9.5 percent; HR 0.76, 95% CI 0.67-0.85). The rate of life-threatening bleeding was increased with prasugrel (1.4 versus 0.9 percent; HR 1.52, 95% CI 1.08-2.13). In a subgroup analysis of net benefit, patients with prior stroke or TIA, age ≥75 years, or body weight less than 60 kg who were assigned to clopidogrel had a lower risk of all-cause death, nonfatal MI, nonfatal stroke, or major bleeding (19 versus 20.2 percent in the prasugrel group) [10].

In the subgroup of 3534 patients who presented with STEMI, the rate of recurrent MI (6.8 versus 9 percent; HR 0.75, 95% CI 0.59-0.95) was lower in the prasugrel group, while the rate of mortality was similar between groups (3.3 versus 4.3 percent in the clopidogrel group; HR 0.76, 95% CI 0.54-0.99) [24].

There is no strong evidence to suggest that early administration of P2Y12 inhibitors is beneficial. Weak evidence that supports the use of P2Y12 receptor blockade prior to angiography comes from the ATLANTIC trial, which showed a small but significant reduction in early stent thrombosis, but there were no differences in ST-resolution or other clinical outcomes [25]. In a retrospective study that included 1624 patients with STEMI, pretreatment with a P2Y12 inhibitor was associated with a lower risk of all-cause death compared with no pretreatment (adjusted HR 0.65, 95% CI 0.44-0.98) [26].

Fibrinolytic therapy — In patients treated with a fibrinolytic agent (algorithm 1) and aspirin, including those for whom PCI is planned following fibrinolysis, we suggest treatment with clopidogrel rather than no P2Y12 inhibitor therapy (algorithm 3). Administration of prasugrel or ticagrelor prior to fibrinolysis is a relative contraindication to fibrinolytic therapy.

Clopidogrel should be given within 24 hours of presentation, typically upon presentation. The loading dose of clopidogrel is 300 mg in patients age 75 years or younger followed by 75 mg daily, while patients >75 years should not receive a loading dose and should start and continue therapy with clopidogrel 75 mg daily [27].

For most patients treated with fibrinolytic therapy alone, we do not switch from clopidogrel to prasugrel or ticagrelor at a later time (eg, prior to discharge). However, for patients who undergo PCI after fibrinolytic therapy, it is reasonable to switch to prasugrel or ticagrelor. In patients <75 years old, we provide a loading dose of clopidogrel if not already provided. If fibrinolysis was administered ≤24 hours prior to the loading dose, the loading dose is clopidogrel 300 mg, and, if >24 hours, the loading dose is clopidogrel 600 mg. In patients ≥75 years, we do not give a loading dose prior to PCI and continue clopidogrel 75 mg daily.

This approach is consistent with North American and European guidelines [4,28].

One large trial of patients with STEMI treated with fibrinolytic therapy and aspirin showed small but statistically significant benefits in reducing mortality and nonfatal reinfarction with administration of clopidogrel, while a smaller trial found no clear benefit on mortality or reinfarction. One trial found similar efficacy and safety of ticagrelor or clopidogrel administered at an average of 11 hours after presentation. The trials include:

●In the COMMIT trial of 45,852 patients with ACS (87 percent with STEMI, 55 percent received fibrinolysis), patients treated with clopidogrel had lower rates of death (7.5 versus 8.1 percent; odds ratio [OR] 0.93, 95% CI 0.87-0.99) and reinfarction (2.1 versus 2.4 percent; OR 0.86, 95% CI 0.76-0.97) compared with patients taking placebo [29]. There was no clear difference in efficacy between patients who received fibrinolysis and those who did not.

●In a trial that included 3491 patients with STEMI treated with fibrinolysis, patients treated with clopidogrel or placebo had similar rates of death (2.6 versus 2.2 percent; OR 1.17, 95% CI 0.75-1.82) and recurrent MI (2.5 versus 3.6 percent; OR 0.7, 95% CI 0.47-1.04) [27]. The composite rate of death, recurrent MI, and poor flow in the infarct artery was lower in patients treated with clopidogrel (15 versus 21.2 percent), which was driven only by differences in infarct artery flow (Thrombolysis In Myocardial Infarction [TIMI] grade 0 or 1 flow 11.7 versus 18.4 percent in the placebo group; OR 0.59, 95% CI 0.48-0.72). The rates of bleeding were similar between groups. The median time between fibrinolytic and study drug administration was 10 minutes (interquartile range [IQR] 5-25).

●In a trial that included 3799 patients with STEMI treated with fibrinolytic therapy and aspirin, patients treated with ticagrelor or clopidogrel at a median of 11.4 (IQR 5.8-18.2) hours after receipt of a fibrinolytic agent had similar rates of fatal and intracranial bleeding and similar rates of all-cause death and recurrent MI [30].

No reperfusion therapy — In patients with STEMI who are not reperfused (algorithm 1), we suggest P2Y12 inhibitor therapy rather than aspirin alone (algorithm 3). We suggest prasugrel or ticagrelor rather than clopidogrel. In patients with risk factors of prior stroke, age >75, or weight <60 kg, we suggest ticagrelor rather than prasugrel due to a possible increase in the risk of bleeding with prasugrel in this population of patients.

The dosing is similar to that for PCI, as discussed elsewhere in this topic. (See 'Primary PCI' above.)

We do not use glycoprotein IIb/IIIa inhibitors in patients with STEMI who do not receive reperfusion therapy.

This approach is consistent with North American and European guidelines [2,4].

Our recommendation for the use of P2Y12 receptor blocker therapy is supported by data from trials that described a small reduction in the rates of mortality (COMMIT) and recurrent MI (COMMIT and CURE) in patients with ACS who did not undergo reperfusion therapy. In the COMMIT/CCS-2 trial of 45,852 patients with acute MI (95 percent with STEMI, 45 percent not reperfused), patients randomly assigned to clopidogrel had a lower rate of mortality than patients assigned to placebo after 28 days of observation (7.5 versus 8.1 percent; OR 0.93, 95% CI 0.87-0.99) and a lower rate of recurrent MI (1.2 versus 1.4 percent; OR 0.81, 95% CI 0.69-0.95) [29,31]. However, these benefits were small. The overall efficacy of clopidogrel was not significantly different among the subgroup of patients not reperfused. The CURE trial is discussed separately. (See "Acute non-ST-elevation acute coronary syndromes: Initial antiplatelet therapy", section on 'Initial therapy (dual antiplatelet therapy)'.)

We suggest that prasugrel is at least as effective as ticagrelor. In a trial (PLATO) that included patients who did not receive PCI or fibrinolytic therapy, ticagrelor was superior to clopidogrel. In this trial, the rate of all-cause death was lower in patients with ACS assigned to ticagrelor compared with clopidogrel (4.5 versus 5.9 percent; HR 0.78, 95% CI 0.69-0.89) [7]. The overall benefit (ie, rate of the primary composite outcome) of ticagrelor was not significantly different among patients with STEMI (8 percent of the sample) who underwent medical management (approximately 20 percent of all patients enrolled did not undergo angiography) compared with invasive management.

SPECIAL CIRCUMSTANCES

Aspirin allergy — For patients with a history of possible aspirin allergy, the optimal approach is not known; options for therapy are discussed separately. (See "Introduction of aspirin to patients with aspirin hypersensitivity requiring cardiovascular interventions", section on 'Indications for urgent aspirin therapy'.)

Patients taking oral anticoagulants — In patients who require anticoagulant therapy and are diagnosed with acute STEMI, it is typical to acutely administer aspirin and P2Y12 inhibitor therapy based on the management strategy, as described elsewhere in this topic (see 'Initial P2Y12 inhibitor by reperfusion strategy' above). Following acute reperfusion (ie, percutaneous coronary intervention [PCI], thrombolysis) or stabilization without reperfusion, the antiplatelet regimen is individualized to the patient's risk of bleeding and recurrent thrombotic events. The long-term approach to antithrombotic therapy in such patients 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'.)

P2Y12 inhibitor therapy at presentation — Our approach to patients taking a P2Y12 inhibitor at the time of presentation is the same (eg, loading doses) as the approach in patients not taking such agents, as discussed elsewhere in this topic. (See 'Initial P2Y12 inhibitor by reperfusion strategy' above.)

Inability to administer an oral P2Y12 inhibitor — In patients who cannot receive an oral P2Y12 inhibitor either prior to or immediately following PCI, it is reasonable to administer cangrelor, an intravenous P2Y12 inhibitor, or, less commonly, a glycoprotein (GP) IIb/IIIa inhibitor:

●Cangrelor – Cangrelor is an intravenous P2Y12 inhibitor that is an option for therapy in patients with STEMI in cardiogenic shock or when an oral P2Y12 inhibitor cannot be administered (eg, patients with nausea and emesis). Cangrelor has similar efficacy compared with either clopidogrel or placebo in three randomized trials that included patients with STEMI [32-34]. (See "Antithrombotic therapy for elective percutaneous coronary intervention: Clinical studies", section on 'Cangrelor'.)

●GP IIb/IIIa inhibitors – For uncommon patients in whom the administration of a GP IIb/IIIa inhibitor at the time of primary PCI may be reasonable, we have a weak preference for tirofiban. The dosing regimens for eptifibatide and tirofiban for patients are based on dosing regimens used in clinical trials:

•Tirofiban – The loading dose of tirofiban is 25 mcg/kg (referred to as the high-bolus dose) given in five minutes or less, which is followed by a continuous infusion of 0.15 mcg/kg/min and continued for up to 18 hours [35]. This dose of tirofiban has shown benefit in small studies but has not been validated in large clinical trials [36,37]. 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 [38-40].

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. The duration of therapy is 18 to 24 hours.

•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. The duration of therapy is 18 to 24 hours.

Complications or poor reflow after PCI — In patients who are found to have no or slow reflow, large thrombus burden, or intraprocedural complications (eg, distal clot embolization, coronary artery dissection), additional antiplatelet therapy is individualized and may include a GP IIb/IIIa inhibitor. The dosing of GP IIb/IIIa inhibitors is discussed elsewhere. (See 'Inability to administer an oral P2Y12 inhibitor' above.)

Routine glycoprotein IIb/IIIa inhibitors — For patients undergoing primary PCI and who received antiplatelet therapy with aspirin and a P2Y12 inhibitor, therapy with an intravenous GP IIb/IIIa inhibitor is reserved for specific scenarios. (See 'Complications or poor reflow after PCI' above and 'Inability to administer an oral P2Y12 inhibitor' above.)

GP IIb/IIIa inhibitors are not used in patients primarily treated with fibrinolysis or medical therapy alone [41].

Trials that evaluated routine use of a GP IIb/IIIa inhibitor did not find consistent benefit on mortality or recurrent MI when used in addition to background P2Y12 inhibitor therapy [42-49].

Trials that compared IIb/IIIa agents with each other found similar efficacy among abciximab, tirofiban, and eptifibatide [45,46,50-58]. We typically choose high-dose tirofiban based on concerns about cost and availability. The intracoronary route has not been shown to be superior to intravenous dosing and is not licensed by the US FDA, European Medicines Agency (eptifibatide), or member European Union countries (abciximab or tirofiban) [59-63]. Abciximab is no longer manufactured.

Planned coronary artery bypass surgery — If coronary artery bypass graft surgery is planned after initial management (eg, PCI, thrombolysis), the decision to continue dual antiplatelet therapy is individualized to patient characteristics that include residual anatomy, whether a stent was placed, and the timing of surgery. These issues are discussed separately. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Preoperative P2Y12 management'.)

OTHER P2Y12 INHIBITOR MANAGEMENT ISSUES

Duration of therapy — Most patients with STEMI, regardless of reperfusion strategy, should continue dual antiplatelet therapy for 12 months unless there are adverse reactions or major bleeding.

The evidence to support treatment for one year is based on the duration of therapy from the CURE, TRITON–TIMI 38, and PLATO trials. The issue of therapy beyond 12 months is discussed in detail separately [64]. (See "Acute non-ST-elevation acute coronary syndromes: Initial antiplatelet therapy", section on 'Other aspects of antiplatelet therapy'.)

Switching ticagrelor or prasugrel to clopidogrel — Either ticagrelor or prasugrel is preferred to clopidogrel as the initial P2Y12 receptor blocker in patients with STEMI undergoing percutaneous coronary intervention (PCI) (see 'Primary PCI' above). However, approximately 10 percent 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 [65-67]. 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 [66,68]:

●For patients who have been receiving ticagrelor, we give the first dose of clopidogrel 12 hours after the last dose of ticagrelor [65,69-71]. 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 taking prasugrel for >5 days, we do not give a loading dose and begin therapy with clopidogrel 75 mg daily.

Switching clopidogrel to ticagrelor or prasugrel — Some patients, such as those who received fibrinolysis followed by PCI, may need to be switched from clopidogrel to either prasugrel or ticagrelor before discharge. Similar to other clinical scenarios, patients with history of stroke or transient ischemic attack, age >75 years, or body weight <60 kg may have a lower risk of bleeding with ticagrelor compared with prasugrel. (See 'Primary PCI' above and 'No reperfusion therapy' above.)

When switching from clopidogrel, we give ticagrelor 180 mg or prasugrel 60 mg at any time within 24 hours of the last dose of clopidogrel. Twelve hours after the loading dose of ticagrelor or prasugrel, we continue with ticagrelor 90 mg twice daily or prasugrel 10 mg daily, respectively [65,72-74].

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".)

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

●Aspirin

•Initial therapy – In patients with suspected or confirmed ST-elevation myocardial infarction (STEMI), we recommend aspirin therapy (Grade 1B) (algorithm 3). The loading dose is uncoated aspirin at a dose of 162 to 325 mg, which should be provided as soon as possible and irrespective of treatment strategy. To promote rapid absorption and effect, the first tablet should be chewed or crushed and should not be enteric coated. (See 'Initial therapy' above.)

•Therapy upon discharge – The approach to aspirin therapy at discharge depends on the type of P2Y12 inhibitor chosen and the need for anticoagulation (see 'Therapy upon discharge' above):

-P2Y12 therapy and no anticoagulation – After the initial aspirin dose, we prescribe aspirin at a dose of 75 to 81 mg once daily rather than at higher doses; there is no benefit from a higher dose, and higher doses increase the likelihood of bleeding from the gastrointestinal tract.

-P2Y12 therapy in patients who require long-term anticoagulation – In patients who have an indication for long-term anticoagulation (eg, atrial fibrillation, mechanical mitral valve), the approach to therapy is discussed separately. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Our approach'.)

●Initial P2Y12 inhibitor use by reperfusion strategy – The approach to antiplatelet therapy is determined by the choice of reperfusion strategy (algorithm 3):

•Primary percutaneous coronary intervention – In patients with STEMI who undergo primary percutaneous coronary intervention (PCI), we recommend treatment with aspirin and a P2Y12 inhibitor rather than other antiplatelet regimens (Grade 1B). We suggest treatment with prasugrel or ticagrelor rather than clopidogrel (Grade 2C). In patients ≥75 years old, history of stroke or transient ischemic attack (TIA), or weight <60 kg, we suggest ticagrelor rather than prasugrel due to a possible increase in the risk of bleeding with prasugrel (Grade 2C). (See 'Primary PCI' above.)

In patients with STEMI, we give a P2Y12 receptor blocker prior to diagnostic coronary angiography whenever possible. Reasons to defer administration until after angiography include uncertainty of diagnosis or if the administration would lead to delays in transfer for PCI. In patients who did not receive oral P2Y12 therapy prior to diagnostic angiography, other reasonable options include initiation of therapy (ie, oral or intravenous P2Y12 inhibitor) prior to PCI or initiation of therapy immediately after PCI. (See 'Inability to administer an oral P2Y12 inhibitor' above.)

•Fibrinolytic therapy – In patients treated with a fibrinolytic agent and aspirin, including those for whom PCI is planned following fibrinolysis, we suggest treatment with clopidogrel rather than no P2Y12 inhibitor therapy (Grade 2C). Administration of prasugrel or ticagrelor prior to fibrinolysis is a relative contraindication to fibrinolytic therapy. (See 'Fibrinolytic therapy' above.)

Clopidogrel should be given within 24 hours of presentation, typically upon presentation.

For most patients treated with fibrinolytic therapy alone, we do not switch from clopidogrel to prasugrel or ticagrelor at a later time (eg, prior to discharge). However, for patients who undergo PCI after fibrinolytic therapy, it is reasonable to switch to prasugrel or ticagrelor. (See 'Switching clopidogrel to ticagrelor or prasugrel' above.)

•No reperfusion therapy – In patients with STEMI who are not reperfused and who will receive aspirin, we suggest additional therapy with a P2Y12 inhibitor rather than aspirin alone (Grade 2C). We suggest prasugrel or ticagrelor rather than clopidogrel (Grade 2C). In patients with risk factors of prior stroke or TIA, age >75 years, or weight <60 kg, we suggest ticagrelor rather than prasugrel (Grade 2C). (See 'No reperfusion therapy' above.)

●Special circumstances

•Aspirin allergy – For patients with a history of possible aspirin allergy, the optimal approach is not known; options for therapy are discussed separately. (See "Introduction of aspirin to patients with aspirin hypersensitivity requiring cardiovascular interventions", section on 'Indications for urgent aspirin therapy'.)

•Patients taking oral anticoagulation – In patients who require anticoagulant therapy and are diagnosed with acute STEMI, it is typical to acutely administer aspirin and P2Y12 inhibitor therapy based on the management strategy, as described elsewhere in this topic. (See 'Initial P2Y12 inhibitor by reperfusion strategy' above.)

The long-term approach to antithrombotic therapy in patients who may have indications 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'.)

•P2Y12 inhibitor therapy at presentation – Our approach to patients taking a P2Y12 inhibitor at the time of presentation is the same (eg, administering a loading dose) as the approach in patients not taking such agents, as discussed elsewhere in this topic. (See 'Initial P2Y12 inhibitor by reperfusion strategy' above.)

•Inability to administer an oral P2Y12 inhibitor – In patients who cannot receive an oral P2Y12 inhibitor either prior to or immediately following PCI, it is reasonable to administer cangrelor, an intravenous P2Y12 inhibitor, or less commonly, a glycoprotein (GP) IIb/IIIa inhibitor. (See 'Inability to administer an oral P2Y12 inhibitor' above.)

•Complications or poor reflow after PCI – Patients with poor flow after PCI, large thrombus burden, or an intraprocedural complication (eg, distal embolization, coronary artery dissection) may benefit from additional antiplatelet therapy. In such patients, additional antiplatelet therapy is individualized and may include a GP IIb/IIIa inhibitor. (See 'Complications or poor reflow after PCI' above.)

•Routine glycoprotein IIb/IIIa inhibitors – For patients undergoing primary PCI and who receive early antiplatelet therapy with aspirin and a P2Y12 inhibitor, therapy with an intravenous GP IIb/IIIa inhibitor is reserved for specific scenarios. (See 'Complications or poor reflow after PCI' above and 'Inability to administer an oral P2Y12 inhibitor' above.)

GP IIb/IIIa inhibitors are not used in patients primarily treated with fibrinolysis or medical therapy alone.

•Planned coronary artery bypass surgery – If coronary artery bypass graft surgery is planned after initial management (eg, PCI, thrombolysis), the decision to continue dual antiplatelet therapy (DAPT) is individualized to patient characteristics that include residual anatomy, whether a stent was placed, and the timing of surgery. These issues are discussed separately. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Preoperative P2Y12 management'.)

●Other P2Y12 inhibitor management issues

•Duration of therapy – Most patients with STEMI, regardless of reperfusion strategy, should continue DAPT for 12 months unless there are adverse reactions or major bleeding. (See 'Duration of therapy' above.)

•Switching from ticagrelor to clopidogrel – For patients who have been receiving ticagrelor, we give the first dose of clopidogrel 12 hours after the last dose of ticagrelor. We give a 600 mg loading dose of clopidogrel to all such patients. (See 'Switching ticagrelor or prasugrel to clopidogrel' above.)

•Switching from prasugrel to clopidogrel - For patients who have been receiving prasugrel for five days or less, some of our experts use a loading dose of clopidogrel 300 mg 24 hours after the last dose of prasugrel, while others do not administer a loading dose. (See 'Switching ticagrelor or prasugrel to clopidogrel' above.)

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 clopidogrel to ticagrelor or prasugrel – When switching from clopidogrel, we give ticagrelor 180 mg or prasugrel 60 mg at any time within 24 hours of the last dose of clopidogrel. Twelve hours after the loading dose, we continue with ticagrelor 90 mg twice daily or prasugrel 10 mg daily. (See 'Switching clopidogrel to ticagrelor or prasugrel' above.)

•Role of genetic testing – We do not perform routine testing for genotypes associated with clopidogrel hyporesponsiveness. (See "Clopidogrel resistance and clopidogrel treatment failure".)

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Topic 94 Version 105.0

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 : 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

3 : 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

4 : 2023 ESC Guidelines for the management of acute coronary syndromes.

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

6 : 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.

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

8 : Aspirin dose and ticagrelor benefit in PLATO: fact or fiction?

9 : Doubts over landmark heart drug trial: ticagrelor PLATO study.

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

11 : 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.

12 : 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.

13 : A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents.

14 : Meta-analysis of trials comparing oral anticoagulation and aspirin versus dual antiplatelet therapy after coronary stenting. Clues for the management of patients with an indication for long-term anticoagulation undergoing coronary stenting.

15 : Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS).

16 : Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study.

17 : Ticlopidine versus oral anticoagulation for coronary stenting.

18 : Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation.

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

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

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

22 : Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial.

23 : 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.

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

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

26 : Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

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

28 : 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.

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

30 : Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial.

31 : Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial.

32 : Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial.

33 : Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial.

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

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

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

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

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

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

40 : 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.

41 : 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.

42 : 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.

43 : 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.

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

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

46 : 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.

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

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

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

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

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

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

53 : 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.

54 : 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.

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

56 : 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.

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

58 : 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.

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

60 : 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.

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

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

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

64 : Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome.

65 : 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.

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

67 : 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.

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

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

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

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

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

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

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