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Antithrombotic therapy in atrial fibrillation with PCI

Combined anticoagulant and antiplatelet therapy for patients with atrial fibrillation or another oral anticoagulant indication who undergo PCI, present with an acute coronary syndrome, or have chronic coronary disease.

Triple therapy, dual antithrombotic therapy, and the population they serve

Triple antithrombotic therapy is the simultaneous use of an oral anticoagulant, aspirin, and a P2Y12 inhibitor. Dual antithrombotic therapy, in this context, is an oral anticoagulant combined with a single antiplatelet agent, almost always clopidogrel. Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor without an anticoagulant, is a different regimen and is covered on the dual antiplatelet therapy page. Anticoagulant monotherapy is the oral anticoagulant alone, the long-term regimen for most patients after the first year.

The population is large. About one patient in ten who undergoes PCI also has atrial fibrillation (AF), and AF develops for the first time during many admissions for ACS. Smaller groups need anticoagulation for venous thromboembolism (VTE), a mechanical heart valve, or left ventricular thrombus. These patients are older and more often have kidney disease, diabetes, heart failure, and prior bleeding, so they carry high thrombotic risk and high bleeding risk simultaneously. They were excluded from the trials that established potent P2Y12 inhibitors and 12-month DAPT, so a separate body of evidence defines their care.

Related pages cover DOAC pharmacology and dosing for all indications (direct oral anticoagulants), choice of anticoagulation for stroke prevention (atrial fibrillation), and antithrombotic therapy after transcatheter valve implantation (transcatheter aortic valve replacement).

Competing thrombotic and bleeding risks after PCI in atrial fibrillation

Three distinct thrombotic processes compete in these patients. Stent thrombosis and spontaneous myocardial infarction are platelet-driven arterial events. They are prevented mainly by antiplatelet therapy, and their risk is highest in the first 30 days after stenting and after ACS. Cardioembolic stroke in AF arises from fibrin-rich thrombus formed in the low-flow left atrial appendage. It is prevented by anticoagulation and only weakly by antiplatelet drugs. Venous thrombosis and prosthetic valve thrombosis are also mainly coagulation-driven. The distinction is not absolute: thrombin is a potent platelet agonist, and an anticoagulant contributes to coronary protection. That contribution explains why a full-dose anticoagulant with clopidogrel protects the stent nearly as well as triple therapy.

Bleeding risk accumulates with each added agent and persists for as long as the combination is taken. Thrombotic risk from the stent declines steeply after the first month, while stroke risk from AF is constant. The time course therefore favors a regimen that is most intense early and steps down.

Major bleeding after PCI is associated with mortality comparable to that of recurrent myocardial infarction. It leads to interruption of antithrombotic therapy, transfusion, and later ischemic events. In WOEST, the first randomized test of omitting aspirin, any bleeding within 1 year occurred in 44.4% of patients on triple therapy with a vitamin K antagonist and in 19.4% on anticoagulant plus clopidogrel.

Three estimates guide the regimen for an individual patient. Stroke risk is estimated to confirm that long-term anticoagulation is indicated. Bleeding risk is estimated to identify modifiable factors and to set the length of each phase. Coronary thrombotic risk is estimated from the clinical presentation and the complexity of the PCI to decide whether aspirin is extended beyond the first week.

Stroke risk: CHA₂DS₂-VASc and CHA₂DS₂-VA

The CHA₂DS₂-VASc score estimates thromboembolic risk in AF and establishes whether long-term anticoagulation is indicated. The 2023 ACC/AHA/ACCP/HRS AF guideline recommends anticoagulation at an estimated annual thromboembolic risk of 2% or more, corresponding to a score of 2 or more in men and 3 or more in women (Class 1). The 2024 European Society of Cardiology (ESC) AF guideline removed female sex and uses CHA₂DS₂-VA, recommending anticoagulation at a score of 2 or more (Class I). Coronary disease itself scores 1 point as vascular disease, so most patients with AF who undergo PCI already meet the threshold.

CHA₂DS₂-VASc score, as derived from the Euro Heart Survey on Atrial Fibrillation. A calculator and the score’s use in stroke prevention decisions are on the atrial fibrillation page.

When the CHA₂DS₂-VASc score is low (0 in men or 1 in women), an anticoagulant is not indicated for AF, and a patient who develops AF after PCI is treated with DAPT according to the coronary indication. When the score is intermediate (1 in men or 2 in women), the decision weighs the modest stroke risk against the added bleeding of combination therapy. Anticoagulation for AF is a lifelong decision, whereas the antiplatelet component after PCI is time-limited, so the presence of a stent does not by itself justify withholding anticoagulation in a patient who meets the threshold.

Bleeding risk: HAS-BLED, ARC-HBR, and PRECISE-DAPT

Three instruments are used in this population, and each answers a different question.

HAS-BLED estimates 1-year major bleeding risk in anticoagulated patients with AF. It assigns 1 point each for uncontrolled hypertension (systolic pressure above 160 mm Hg), abnormal kidney function, abnormal liver function, prior stroke, prior bleeding or bleeding predisposition, labile international normalized ratio (INR), age over 65 years, antiplatelet or nonsteroidal anti-inflammatory drug use, and alcohol excess. A score of 3 or more identifies high bleeding risk. Its main use is to flag modifiable factors (blood pressure, labile INR, concomitant nonsteroidal drugs, alcohol). A high score is not a reason to withhold anticoagulation, and the 2024 ESC AF guideline recommends against using bleeding scores to decide whether to start or stop an anticoagulant.

The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria define high bleeding risk after PCI as a 1-year risk of Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding of 4% or more, or of intracranial hemorrhage of 1% or more. Anticipated long-term oral anticoagulation is itself a major criterion, so every patient on this page meets the ARC-HBR definition. Within this population, the criteria other than anticoagulation identify the patients at greatest risk, and the 2025 ACC/AHA ACS guideline adopted the criteria as its definition of high bleeding risk.

ARC-HBR criteria from the Academic Research Consortium consensus document on high bleeding risk, as reproduced in Table 22 of the 2025 ACC/AHA ACS guideline. High bleeding risk is present with at least 1 major or 2 minor criteria. eGFR, estimated glomerular filtration rate.

PRECISE-DAPT combines age, creatinine clearance, hemoglobin, white cell count, and prior spontaneous bleeding to estimate out-of-hospital bleeding on DAPT. A score of 25 or more identifies high bleeding risk. It was derived in patients not taking anticoagulants and is used in this population to grade bleeding risk among patients who already meet ARC-HBR. A calculator is on the dual antiplatelet therapy page.

For decisions about combination therapy, the ARC-HBR features beyond the anticoagulant itself are the most useful markers. Examples are prior major bleeding, anemia, thrombocytopenia, advanced kidney disease, active cancer, prior intracranial hemorrhage, and age 75 years or older combined with another minor criterion. In these patients, aspirin stops at discharge, and the antiplatelet agent can stop before the default duration.

Bleeding definitions used in the trials: BARC, ISTH, and TIMI

The primary endpoints of the dual-therapy trials used different bleeding scales. Cross-trial comparison of event rates is therefore unreliable.

Bleeding definitions: International Society on Thrombosis and Haemostasis (ISTH), Thrombolysis in Myocardial Infarction (TIMI), and Bleeding Academic Research Consortium (BARC). The ISTH major bleeding definition is a 2005 recommendation for nonsurgical patients, and the BARC scale is a 2011 consensus report for cardiovascular trials.

Clinically relevant nonmajor bleeding is more frequent than major bleeding with combination therapy, and it can lead patients and clinicians to stop antithrombotic drugs early. Premature discontinuation of the anticoagulant or the P2Y12 inhibitor is itself a cause of stroke and stent thrombosis.

High thrombotic risk features that extend aspirin

The 2023 AF guideline and the 2025 ACS guideline allow aspirin to continue up to 30 days after PCI when the perceived risk of stent thrombosis is high. The US documents give examples without a formal list: complex revascularization, multivessel PCI, and previous stent thrombosis. The 2020 ACC expert consensus decision pathway (ECDP) adds bifurcation lesions, thrombus-containing lesions, and long lesions as higher-risk lesion characteristics. The 2023 ESC ACS guideline lists clinical, procedural, and anatomic features of high ischemic risk.

Features of high thrombotic risk after PCI, compiled from the 2023 ESC ACS guideline, the 2020 ACC decision pathway, and the 2023 ACC/AHA/ACCP/HRS AF guideline. No validated score combines these features for patients taking anticoagulants.

Many of these features cluster with bleeding risk factors in older patients with diabetes and kidney disease. When both risks are high, the US documents give priority to bleeding prevention and stop aspirin at discharge. In the trial-level meta-analyses, the excess stent thrombosis with dual therapy was small and the bleeding reduction was large in both ACS and stable presentations. The 30-day extension is therefore reserved for patients in whom the thrombotic concern is specific and bleeding risk is not high.

Evidence from the dual-therapy trials

Six randomized trials define the early phase after PCI. The table also lists OPTIMA-AF, which tested stopping the P2Y12 inhibitor at 1 month, and AFIRE, which tested the chronic phase. WOEST and ISAR-TRIPLE used vitamin K antagonists and tested the antiplatelet component. The four DOAC trials (PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, and ENTRUST-AF PCI) compared DOAC-based dual therapy with warfarin-based triple therapy. Only AUGUSTUS separated the effect of the anticoagulant from the effect of aspirin.

Randomized trials of antithrombotic regimens after PCI in patients taking an oral anticoagulant. Rates are listed in the order of the regimens compared. HR, hazard ratio; MI, myocardial infarction; VKA, vitamin K antagonist. Trials of the chronic phase are compared in a separate table below.

WOEST. The trial randomized 573 patients taking a vitamin K antagonist who underwent PCI in Belgium and the Netherlands to clopidogrel alone or clopidogrel plus aspirin for 1 to 12 months; about two-thirds received the assigned regimen for 12 months. Any bleeding fell from 44.4% to 19.4%, and transfusion from 9.5% to 3.9%. Thrombotic events were not increased, and all-cause mortality was lower with dual therapy. The trial was open-label, used any bleeding as its endpoint, was underpowered for stent thrombosis, and included patients with ACS in only about one-quarter. It nevertheless established the principle that the aspirin component carries much of the bleeding cost.

ISAR-TRIPLE. This trial tested the opposite approach, a shorter course of P2Y12 inhibitor with continued aspirin. Six weeks versus 6 months of clopidogrel on a background of aspirin and a vitamin K antagonist produced no difference in the net composite or in TIMI major bleeding. Shortening clopidogrel while keeping aspirin did not reduce bleeding, and every later trial omitted aspirin and retained the P2Y12 inhibitor.

PIONEER AF-PCI. The trial randomized 2,124 patients with nonvalvular AF after stenting to three strategies. Group 1 received rivaroxaban 15 mg daily (10 mg with creatinine clearance 30 to 50 mL/min) plus a P2Y12 inhibitor for 12 months. Group 2 received rivaroxaban 2.5 mg twice daily plus DAPT for 1, 6, or 12 months. Group 3 received a dose-adjusted vitamin K antagonist plus DAPT. Clinically significant bleeding was 16.8%, 18.0%, and 26.7%, respectively. Cardiovascular death, myocardial infarction, or stroke occurred in 6.5%, 5.6%, and 6.0%. Neither rivaroxaban dose is the labeled AF dose of 20 mg, and the trial was not powered for stroke prevention. The 15-mg dose with a P2Y12 inhibitor was adopted by the 2020 ACC ECDP. The 2.5-mg twice-daily dose is a vascular dose and is not used for stroke prevention.

RE-DUAL PCI. Patients were randomized to dabigatran 110 mg or 150 mg twice daily with clopidogrel or ticagrelor and no aspirin, or to warfarin triple therapy with aspirin for 1 to 3 months. Outside the United States, patients aged 80 years or older (70 or older in Japan) could receive only the 110-mg dose or triple therapy, so the 150-mg comparison excluded these older patients. Both doses reduced bleeding. Dual therapy with both doses combined was noninferior for the composite of thromboembolic events, death, or unplanned revascularization (13.7% vs. 13.4%). Myocardial infarction and stent thrombosis were numerically more frequent with the 110-mg dose and not with the 150-mg dose. About 12% of patients received ticagrelor, the largest experience with ticagrelor in combination with a DOAC.

AUGUSTUS. The largest trial randomized 4,614 patients with AF and a recent ACS or PCI who were planned to take a P2Y12 inhibitor (clopidogrel in more than 90%). Randomization was open-label to apixaban or a vitamin K antagonist and double-blind to aspirin or placebo, for 6 months. The population included 23.9% with medically managed ACS, 37.3% with ACS treated by PCI, and 38.8% with elective PCI. Apixaban reduced ISTH major or clinically relevant nonmajor bleeding (10.5% vs. 14.7%) and death or hospitalization (23.5% vs. 27.4%), with similar ischemic events. Aspirin increased bleeding (16.1% vs. 9.0%) without a significant reduction in the composite of death or ischemic events. The two factors did not interact. The safest regimen, apixaban plus a P2Y12 inhibitor without aspirin, had about half the bleeding of warfarin triple therapy.

ENTRUST-AF PCI. Edoxaban 60 mg daily (30 mg with creatinine clearance 15 to 50 mL/min, weight 60 kg or less, or specified P-glycoprotein inhibitors) plus a P2Y12 inhibitor was compared with vitamin K antagonist triple therapy. Aspirin in the control arm was given for 1 to 12 months. Major or clinically relevant nonmajor bleeding at 12 months was 17% versus 20%, which met noninferiority but not superiority. Randomization occurred a median of 45 hours after PCI. In a post hoc landmark analysis, bleeding with the warfarin regimen was lower in the first 2 weeks, when the INR was often subtherapeutic, and edoxaban was superior thereafter.

Features common to the four DOAC trials. All four DOAC trials were open-label for the anticoagulant, powered for bleeding and not for stent thrombosis or stroke, and enrolled patients at intermediate, not extreme, thrombotic risk. Aspirin was given before randomization, so the dual-therapy arms began with a short period of triple therapy. The 2020 ACC ECDP lists the aspirin exposure in the dual-therapy arms as about 4 hours in WOEST, 72 hours in PIONEER AF-PCI, 1.6 days in RE-DUAL PCI, 5 days in ENTRUST-AF PCI, and 7 days in AUGUSTUS. The trials therefore tested early, not immediate, aspirin withdrawal. Clopidogrel was the P2Y12 inhibitor in most patients in every trial.

Meta-analyses: the stent thrombosis cost of omitting aspirin

Individual trials could not exclude a modest increase in coronary events with dual therapy, and pooled analyses addressed that question.

A 2019 meta-analysis of the four DOAC trials (10,234 patients) found that dual therapy reduced ISTH major or clinically relevant nonmajor bleeding compared with triple therapy (13.4% vs. 20.8%; relative risk 0.66) and reduced intracranial hemorrhage by about two-thirds. Stent thrombosis was more frequent with dual therapy (1.0% vs. 0.6%; relative risk 1.59), and myocardial infarction showed a borderline increase (3.6% vs. 3.0%). All-cause death, major adverse cardiovascular events, and stroke did not differ. A second analysis by clinical presentation found the same pattern in ACS and in stable coronary disease, with no interaction. In both, the coronary excess was concentrated in patients assigned dabigatran 110 mg, a dose below the stroke-prevention dose used for most patients in the United States.

A Bayesian network meta-analysis of WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS (10,026 patients) found less TIMI major bleeding with a DOAC plus a P2Y12 inhibitor than with a vitamin K antagonist plus DAPT (odds ratio 0.49), without significant differences in major adverse cardiovascular events. It concluded that a vitamin K antagonist plus DAPT should generally be avoided. The meta-analysis cited by the 2023 AF guideline found an increase in stent thrombosis with dual therapy (odds ratio 1.67). The number needed to treat to prevent one ISTH major bleed was 42, against a number needed to harm of 223 for one stent thrombosis.

The timing of stent thrombosis shapes the aspirin window. In AUGUSTUS, about 80% of stent thromboses occurred within 30 days of PCI, and they were numerically less frequent with aspirin than with placebo. A post hoc analysis of AUGUSTUS divided the 6 months into two periods. From randomization to 30 days, aspirin increased severe bleeding by 0.97 percentage points and reduced severe ischemic events by 0.91 percentage points, an approximately equal trade-off. From 30 days to 6 months, aspirin increased severe bleeding by 1.25 percentage points and did not reduce ischemic events. These data underpin the US window of 1 to 4 weeks, with extension to 30 days in selected patients and no aspirin beyond that point.

US guideline recommendations and European differences

The four US documents are consistent and differ mainly in the population addressed. The 2023 AF guideline covers AF with ACS or PCI and AF with chronic coronary disease. The 2025 ACS guideline covers any anticoagulant indication after ACS. The 2023 chronic coronary disease guideline covers elective PCI. The 2020 ACC ECDP gives the most detailed practical pathway, including VTE and periprocedural management.

US recommendations on combined anticoagulant and antiplatelet therapy. LOE, level of evidence. The ECDP is an expert consensus document without classes of recommendation. Recommendation text follows the published guidelines and their posted corrections.

European guidance. The 2023 ESC ACS guideline and the 2024 ESC chronic coronary syndrome guideline set a shorter default aspirin period: triple therapy for up to 1 week, then an oral anticoagulant and clopidogrel for 12 months after ACS (Class I) or 6 months after elective PCI (Class I), then anticoagulant alone. Triple therapy for up to 1 month is reserved for high ischemic risk (Class IIa). After ACS, dual therapy can stop at 6 months when bleeding risk predominates (Class IIb). The 2023 ESC ACS guideline lists rivaroxaban 15 mg or 20 mg and dabigatran 110 mg or 150 mg as the doses used in combination with antiplatelet therapy. The 2020 ACC ECDP likewise uses rivaroxaban 15 mg daily (10 mg with creatinine clearance 30 to 50 mL/min) with a P2Y12 inhibitor. Dabigatran 110 mg twice daily has no US counterpart, because that dose is not approved for AF in the United States.

Periprocedural management: anticoagulant interruption, heparin, access, and stent

Elective and urgent PCI. When coronary angiography can be deferred briefly, the 2020 ACC ECDP recommends holding a vitamin K antagonist until the INR is 2.0 or lower (some laboratories use 1.5 or lower, and the threshold depends on access site). For DOACs, the hold interval depends on the drug, kidney function, and access route. No bridging is used for DOACs, because low-molecular-weight heparin has similar pharmacokinetics and adds bleeding.

Recommended DOAC hold intervals before elective PCI, from Table 5 of the 2020 ACC expert consensus decision pathway. Intervals are adapted to operator and institutional practice.

Emergency PCI. In ST-elevation myocardial infarction or high-risk non-ST-elevation ACS, the anticoagulant is stopped and PCI proceeds without delay. In patients taking a DOAC, the activated clotting time is not a reliable measure of anticoagulant effect. Radial access is used whenever feasible, and procedural anticoagulation is given according to ACS dosing guidance.

Antiplatelet loading. All patients receive aspirin 162 to 325 mg before or at the procedure. Because clopidogrel is the P2Y12 inhibitor used with an anticoagulant, the ECDP specifies a 600-mg clopidogrel loading dose at PCI. The 2025 ACS guideline lists clopidogrel loading doses of 300 or 600 mg. Patients already taking clopidogrel do not need routine reloading for elective PCI.

Procedural anticoagulation. Unfractionated heparin, enoxaparin, and bivalirudin are acceptable during PCI, with standard ACC/AHA dosing. In patients not previously anticoagulated, unfractionated heparin is given as a 70 to 100 U/kg bolus to an activated clotting time of 250 to 300 seconds. A glycoprotein IIb/IIIa inhibitor or cangrelor is reserved for large thrombus burden or procedural thrombotic complications, because both add bleeding in anticoagulated patients.

Access, stent, and imaging. Radial access is recommended over femoral access in ACS (2025 ACS guideline, Class 1) to reduce bleeding, vascular complications, and death. When femoral access is required, ultrasound guidance and closure devices reduce access-site bleeding. A newer-generation drug-eluting stent is preferred over a bare-metal stent in all patients, including those at high bleeding risk (2021 ACC/AHA/SCAI revascularization guideline, Class 1). In trials of patients at high bleeding risk or of advanced age given 1 to 6 months of DAPT (LEADERS FREE, ZEUS, and SENIOR), drug-eluting stents reduced ischemic events, including repeat revascularization, compared with bare-metal stents. Intravascular imaging that secures full stent expansion lowers stent thrombosis risk, which supports early aspirin withdrawal.

Resumption of the anticoagulant. In most patients, the anticoagulant is resumed within 24 hours after PCI, as early as the evening of the procedure once access-site hemostasis is secure. The ECDP recommends a DOAC after PCI regardless of the anticoagulant used before, when a DOAC is appropriate. In patients who resume a vitamin K antagonist without bridging, aspirin can continue with the P2Y12 inhibitor until the INR is therapeutic. When a DOAC replaces warfarin, apixaban and dabigatran are started when the INR falls below 2.0, rivaroxaban below 3.0, and edoxaban at 2.5 or less, according to the US prescribing information.

Periprocedural triple therapy and when aspirin stops

Aspirin is given at the time of PCI and for a short period afterward because the risk of stent thrombosis is highest in the first days and weeks. The maintenance dose during triple therapy is 81 mg daily. The ECDP specifies that aspirin combined with an anticoagulant does not exceed 100 mg daily.

The default in the ECDP is to stop aspirin before or at hospital discharge in most patients. The 2023 AF guideline and the 2025 ACS guideline define a window of 1 to 4 weeks, and the 2023 ESC ACS guideline sets up to 1 week as the default. In practice, these documents converge: aspirin stops at discharge or within the first week for most patients, and continues to 30 days for the minority whose thrombotic risk is high and bleeding risk is not.

Extension to 30 days. The 2023 AF guideline states that triple therapy up to 30 days is a consideration when the perceived risk of stent thrombosis is high, citing complex revascularization, multivessel PCI, and prior stent thrombosis. The 2023 chronic coronary disease guideline rates continuation of aspirin with clopidogrel for up to 1 month as reasonable with high thrombotic risk and low bleeding risk (Class 2a). The AUGUSTUS timing analysis provides the rationale. In the first 30 days the absolute ischemic benefit of aspirin roughly equals its bleeding cost, and after 30 days only the bleeding cost remains.

Triple therapy beyond 30 days. No contemporary document supports routine triple therapy beyond 1 month. ISAR-TRIPLE found no bleeding reduction from a 6-week course of clopidogrel compared with a 6-month course when aspirin was continued. AUGUSTUS showed that aspirin from 30 days to 6 months increased bleeding without ischemic benefit. Triple therapy commonly continues beyond the intended period because the stop date was not communicated at discharge. A stop date written in the discharge summary and the medication list addresses this cause.

Very early aspirin withdrawal. Omitting aspirin entirely from the time of PCI has not been tested in anticoagulated patients. In the DOAC trials, all patients received aspirin before randomization. For that reason, a periprocedural course of aspirin, even if only until discharge, remains the default.

Choice of P2Y12 inhibitor with an oral anticoagulant

Clopidogrel. Clopidogrel is the P2Y12 inhibitor of choice with an anticoagulant. The 2025 ACS guideline recommends a P2Y12 inhibitor, preferably clopidogrel, and the 2023 chronic coronary disease guideline specifies clopidogrel after elective PCI. The trials that established ticagrelor and prasugrel as superior to clopidogrel in ACS excluded patients requiring long-term anticoagulation, and both agents cause more bleeding than clopidogrel. In the DOAC trials, clopidogrel was used in most patients.

Ticagrelor. The ECDP states that ticagrelor may be used in place of clopidogrel in patients at particularly high risk of stent thrombosis, such as some patients with ACS, while acknowledging limited data. About 12% of RE-DUAL PCI patients, in the dabigatran and warfarin arms, received ticagrelor, and smaller proportions received it in PIONEER AF-PCI, AUGUSTUS, and ENTRUST-AF PCI. Ticagrelor is not used as part of triple therapy. When ticagrelor is chosen, it is combined with the anticoagulant alone, without aspirin beyond the periprocedural period.

Prasugrel. Prasugrel is avoided with an anticoagulant. In an observational study of triple therapy with a vitamin K antagonist, aspirin, and prasugrel after drug-eluting stent implantation, bleeding was about 4-fold higher than with clopidogrel-based triple therapy. Prasugrel is also contraindicated after stroke or transient ischemic attack, a common history in patients with AF.

Switching at the transition to dual therapy. Patients loaded with ticagrelor or prasugrel before the need for anticoagulation was recognized, or before new AF developed, are switched to clopidogrel when the anticoagulant is started. After ticagrelor, a 600-mg clopidogrel loading dose is given 24 hours after the last ticagrelor dose. Switching protocols for each agent are covered on the antiplatelet therapy page.

CYP2C19 genotype and platelet function testing. Clopidogrel is a prodrug activated mainly by CYP2C19, and carriers of loss-of-function alleles generate less active metabolite. The ECDP concluded that platelet function and genotype testing in clopidogrel-treated patients have not shown a clear thrombotic benefit for routine use, and none of the US guidelines recommends routine testing in anticoagulated patients. No randomized trial has tested genotype-guided P2Y12 selection in patients taking an oral anticoagulant. When a patient on clopidogrel and an anticoagulant has stent thrombosis, genotype or platelet function testing can inform the choice of an alternative agent.

Choice and dose of the oral anticoagulant

DOAC or warfarin. A DOAC is preferred over a vitamin K antagonist in combination with antiplatelet therapy (2023 AF guideline, Class 1, LOE A). In a meta-analysis cited by the guideline, DOAC-based regimens reduced major bleeding by 42% relative to warfarin-based regimens, without a difference in ischemic events. AUGUSTUS isolated the anticoagulant effect: apixaban reduced bleeding by 31% and death or hospitalization by 17% compared with a vitamin K antagonist, independent of aspirin. DOACs also avoid the early period of unstable INR after PCI and the need for bridging. Warfarin remains the anticoagulant for mechanical heart valves, moderate to severe rheumatic mitral stenosis, triple-positive antiphospholipid syndrome, and patients for whom DOACs are contraindicated or unavailable.

Full dose, not empiric reduction. The anticoagulant is given at the dose that prevents stroke, with dose reduction only when the drug’s own criteria are met. The DOAC trials tested apixaban 5 mg twice daily, edoxaban 60 mg daily, and dabigatran 150 mg twice daily at their stroke-prevention doses. Reducing the dose because antiplatelet therapy is being added sacrifices stroke protection without proven bleeding benefit. The two exceptions supported by trial data are the rivaroxaban 15-mg dose from PIONEER AF-PCI and, outside the United States, dabigatran 110 mg.

Oral anticoagulant doses in combination with a P2Y12 inhibitor after PCI for AF. Creatinine clearance by the Cockcroft–Gault equation with actual body weight. Dosing for VTE is higher; see the section on other anticoagulation indications.

Choice among DOACs. No trial has compared DOACs with each other in this setting, and all four are acceptable when dosed correctly. Apixaban has the largest evidence base in AF with PCI, a factorial design that separated the anticoagulant effect from aspirin, and the largest bleeding advantage over warfarin. Rivaroxaban and edoxaban are taken once daily. Dabigatran requires adequate kidney function and has a specific reversal agent. A patient already stable on a DOAC before PCI usually continues the same drug.

Drug interactions. All DOACs are substrates of P-glycoprotein, and apixaban and rivaroxaban are also metabolized by CYP3A4. Strong inducers of both pathways (rifampin, carbamazepine, phenytoin, and St John’s wort) lower DOAC levels and are avoided. Strong combined inhibitors raise DOAC levels and bleeding risk. Several antiarrhythmic drugs used in AF, including dronedarone, verapamil, and amiodarone, increase dabigatran and edoxaban exposure, and the labels specify dose adjustment for some combinations. Nonsteroidal anti-inflammatory drugs and other antiplatelet agents add bleeding without pharmacokinetic interaction. Interaction tables are on the direct oral anticoagulants page.

Warfarin intensity. When warfarin is required, the ECDP recommends the lower part of the therapeutic range, INR 2.0 to 2.5, with more frequent monitoring and attention to time in therapeutic range. The INR target for a mechanical valve is not lowered. Details of INR management are on the warfarin page.

Antithrombotic regimen planner

The planner applies the US recommendations to a single patient. It returns the anticoagulant dose for combination therapy and the sequence of regimens from PCI to beyond 12 months. Kidney function is estimated by the Cockcroft–Gault equation with actual body weight.

Creatinine clearance = (140 − age) × weight (kg) ÷ (72 × serum creatinine), × 0.85 in women. Regimens follow the 2023 ACC/AHA/ACCP/HRS AF guideline, the 2025 ACC/AHA ACS guideline, the 2023 AHA/ACC chronic coronary disease guideline, and the 2020 ACC expert consensus decision pathway. The planner does not apply to patients with active bleeding, recent intracranial hemorrhage, or a creatinine clearance below 15 mL/min on dialysis, in whom regimens are individualized.

Antithrombotic timeline from PCI to 12 months and beyond

The timeline integrates the presentation, bleeding risk, and thrombotic risk into a sequence of regimens.

Antithrombotic sequence after PCI in patients taking an oral anticoagulant, synthesized from the 2023 ACC/AHA/ACCP/HRS AF guideline, the 2025 ACC/AHA ACS guideline, the 2023 AHA/ACC chronic coronary disease guideline, and the 2020 ACC expert consensus decision pathway. A proton pump inhibitor is given throughout the combination period.

Patients with ACS compared with elective PCI

The clinical presentation sets the duration of the P2Y12 inhibitor, not the duration of aspirin. After ACS, clopidogrel continues with the anticoagulant for 12 months; after elective PCI, it continues for 6 months by default. The 2025 ACS guideline adds that the P2Y12 inhibitor can stop earlier in patients with multiple bleeding risk factors.

ACS was expected to carry greater thrombotic risk with dual therapy, but the trial data did not show a differential effect. In the meta-analysis by clinical presentation (10,193 patients, 5,675 with ACS), dual therapy reduced bleeding, including intracranial hemorrhage, to the same degree in ACS and in stable presentations. The small excess in myocardial infarction and stent thrombosis was also similar in both groups, with no interaction. In the AUGUSTUS subgroup analysis, apixaban reduced bleeding compared with a vitamin K antagonist in ACS treated with PCI (HR 0.68) and in elective PCI (HR 0.82). Aspirin increased bleeding to a similar degree in both groups (HR 2.02 and 1.91) without a difference in death or ischemic events. ACS presentation therefore does not, by itself, justify extending aspirin. It is one of the factors weighed with the procedural features listed above.

ST-elevation myocardial infarction. Patients with ST-elevation myocardial infarction were represented in all DOAC trials but in smaller numbers. The thrombus burden and the early risk of stent thrombosis are highest in this group, and extension of aspirin to 30 days is more often chosen when bleeding risk allows. Left ventricular thrombus after anterior infarction can create a second anticoagulant indication; it is discussed below.

Elective PCI and the trend to shorter therapy. The 2023 chronic coronary disease guideline sets clopidogrel for 6 months after elective PCI. Recent data suggest that some patients need less. In the anticoagulated cohort of MASTER DAPT (1,666 patients at high bleeding risk, randomized 1 month after PCI), the abbreviated strategy was a single antiplatelet agent to 6 months followed by the anticoagulant alone. The standard strategy was at least 2 more months of DAPT, then a single antiplatelet agent to 12 months. Net adverse clinical events (HR 0.83) and major adverse cardiac and cerebral events (HR 0.88) did not differ, and bleeding was numerically lower. OPTIMA-AF (1,088 patients in Japan, 94% with chronic coronary syndrome, PCI with intravascular imaging) compared 1 month of dual therapy followed by DOAC monotherapy with 12 months of dual therapy. Death or thromboembolic events were 5.4% versus 4.3% (HR 1.25), which met noninferiority. Major or clinically relevant nonmajor bleeding at 12 months was 4.5% versus 8.8% (HR 0.50). All-cause mortality was numerically higher with 1 month (4.1% vs. 2.8%), mainly from noncardiovascular deaths. Event rates were lower than expected, so the efficacy estimate is imprecise. These trials support stopping antiplatelet therapy early in stable patients at high bleeding risk, and they do not yet change the US default.

Medically managed ACS. About one-quarter of AUGUSTUS patients had ACS managed without PCI. In this group, apixaban reduced bleeding by more than half compared with a vitamin K antagonist (HR 0.44) and reduced death or hospitalization (HR 0.71). Aspirin added to apixaban and a P2Y12 inhibitor increased bleeding (HR 1.49) without reducing ischemic events. The usual regimen is the anticoagulant plus clopidogrel for up to 12 months, without aspirin after the acute phase, followed by anticoagulant monotherapy. The ECDP gives the same 12-month course.

Transition to anticoagulant monotherapy at 12 months and in chronic coronary disease

Beyond the first year, the anticoagulant alone protects against both stroke and coronary events in most patients, and adding an antiplatelet agent mainly adds bleeding. The 2023 AF guideline recommends oral anticoagulant monotherapy over an anticoagulant plus a single antiplatelet agent in patients with AF and chronic coronary disease without prior stent thrombosis (Class 1, B-R). Chronic coronary disease in this recommendation means more than 1 year after revascularization or coronary disease not requiring revascularization. The randomized evidence now includes five trials.

Randomized trials of anticoagulant monotherapy or added antiplatelet therapy in the chronic phase after PCI. CABG, coronary artery bypass grafting.

AFIRE provided the main evidence for the 2023 AF guideline recommendation. Rivaroxaban monotherapy was noninferior for cardiovascular events and death and superior for major bleeding, and all-cause mortality was lower with monotherapy. AFIRE used the Japanese rivaroxaban doses of 10 and 15 mg daily. EPIC-CAD and ADAPT AF-DES extended the finding to edoxaban and to DOACs with clopidogrel, with net benefit driven by large reductions in bleeding and no increase in ischemic events. AQUATIC added a placebo-controlled test in patients selected for high atherothrombotic risk, the group most often kept on aspirin. Aspirin increased major bleeding threefold, did not reduce ischemic events, and was associated with higher all-cause mortality.

Limitations of the chronic-phase trials. Four of the five trials enrolled only East Asian patients, and most were open-label. All excluded patients with prior stent thrombosis. The 2023 AF guideline recommendation applies to patients without prior stent thrombosis, and the ECDP regards continuing a single antiplatelet agent beyond 12 months as reasonable in selected patients with very high thrombotic risk (prior myocardial infarction with complex lesions or extensive atherosclerosis) and low bleeding risk. AQUATIC weakens the case for aspirin even in that group.

At the 12-month visit. The P2Y12 inhibitor is stopped and the anticoagulant continued alone. The rivaroxaban dose returns from the PIONEER AF-PCI dose to the labeled dose of 20 mg (15 mg with creatinine clearance 50 mL/min or less). The proton pump inhibitor is stopped unless another indication exists.

New atrial fibrillation in a patient already taking antiplatelet therapy

AF often appears after PCI or ACS in a patient already taking DAPT. The 2020 ACC ECDP organizes the response by the indication for antiplatelet therapy and the time since the event.

Management of new AF in patients taking antiplatelet therapy, from the 2020 ACC expert consensus decision pathway (Figure 4). Anticoagulation is started only when the stroke-risk threshold is met.

AF that appears only during the first days after ACS or cardiac surgery is still associated with later recurrence and stroke. The decision to anticoagulate follows the CHA₂DS₂-VASc assessment, with the same combination rules applied when the patient also has a recent stent. Device-detected subclinical AF is covered on the atrial fibrillation page.

Other anticoagulation indications: venous thromboembolism, left ventricular thrombus, mechanical valves, and transcatheter valves

Venous thromboembolism. VTE accounts for a small fraction of anticoagulated patients undergoing PCI, and the trials of dual therapy enrolled almost none. The 2020 ACC ECDP extrapolates from AF with three VTE-specific adjustments.

• Timing. If a time-limited course of anticoagulation (for example, 3 months after VTE provoked by surgery) is under way and PCI is elective, PCI is deferred until the course is complete and the anticoagulant stopped.
• Dose. VTE treatment doses are used, not the AF combination doses: rivaroxaban 20 mg daily (not 15 mg), apixaban 5 mg twice daily, dabigatran 150 mg twice daily, or edoxaban 60 mg daily. After at least 6 months of treatment in patients on indefinite therapy, reduced-dose apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily can be considered. With the reduced dose, long-term single antiplatelet therapy is retained, because the reduced dose was not designed for coronary protection.
• Duration. When the VTE course ends before the coronary antiplatelet course, the patient returns to the standard DAPT or single antiplatelet regimen for the remainder of the post-PCI period. When anticoagulation is indefinite, the AF sequence applies.

In patients with cancer-associated VTE, a DOAC or low-molecular-weight heparin is used, and patients with gastrointestinal or genitourinary cancers have more bleeding at those sites with DOACs. VTE duration decisions are covered on the venous thromboembolism treatment page and cancer-related issues on the cancer-associated thrombosis page.

Left ventricular thrombus. Left ventricular thrombus after myocardial infarction has become less common with timely primary PCI and is concentrated after anterior ST-elevation infarction with an ejection fraction below 30% or an apical aneurysm. The 2025 ACS guideline states that most patients warrant anticoagulation for about 3 months, with repeat imaging to decide whether a longer course is needed. DOACs are widely used, and observational studies and small trials suggest similar efficacy to warfarin with less bleeding (2022 AHA scientific statement). During anticoagulation, the combination rules for AF apply: aspirin for 1 to 4 weeks, then the anticoagulant plus clopidogrel. When the thrombus resolves and anticoagulation stops, the ECDP principle for time-limited anticoagulation applies: antiplatelet therapy reverts to the standard DAPT regimen for the remainder of the post-ACS course. Detection and treatment are covered on the left ventricular thrombus page.

Mechanical heart valves. DOACs are contraindicated with mechanical valves; dabigatran caused more thromboembolism and more bleeding than warfarin in RE-ALIGN. Warfarin is continued at the valve-specific INR target (2.5 for a current-generation bileaflet aortic prosthesis without risk factors; 3.0 for a mechanical mitral prosthesis or an aortic prosthesis with risk factors), and the target is not lowered for combination therapy. About one in ten WOEST patients had a mechanical valve, and the 2025 ACS guideline recommendation to stop aspirin after 1 to 4 weeks covers all anticoagulant indications, including prosthetic valves. The usual regimen is warfarin plus clopidogrel after a short course of aspirin, with antiplatelet duration determined by the coronary indication. Evidence in this group is limited, and the 2020 ACC ECDP excluded prosthetic valves from its recommendations. Management of anticoagulation for valve prostheses is covered on the prosthetic heart valves page.

Transcatheter aortic valve replacement. Patients undergoing transcatheter aortic valve replacement (TAVR) often have both AF and coronary stents. Two trials define the principle that an anticoagulated patient after TAVR does not need an added antiplatelet agent for the valve itself. In POPular TAVI cohort B (313 patients with an anticoagulant indication), bleeding at 12 months occurred in 21.7% with the anticoagulant alone and in 34.6% with added clopidogrel, without a difference in thromboembolic events. In ENVISAGE-TAVI AF (1,426 patients with AF), edoxaban was noninferior to a vitamin K antagonist for net adverse events but caused more major bleeding (9.7 vs. 7.0 per 100 person-years), mostly gastrointestinal.

When a coronary stent has been placed recently, the stent determines the antiplatelet component and its duration, following the timeline above. The valve does not add an aspirin indication. When PCI and TAVR are staged, the antiplatelet clock starts at the PCI. Full TAVR antithrombotic recommendations are on the transcatheter aortic valve replacement page.

Peripheral artery disease and left atrial appendage occlusion

Peripheral artery disease. In patients with AF and stable peripheral artery disease, the 2023 AF guideline rates anticoagulant monotherapy over dual therapy as reasonable to reduce bleeding (Class 2a, B-NR). After endovascular peripheral intervention, the ECDP gives the anticoagulant with a single antiplatelet agent, clopidogrel preferred, for the usual 1 to 3 months of post-procedure antiplatelet therapy, followed by the anticoagulant alone. Carotid stenting is managed in the same way.

Low-dose rivaroxaban. Rivaroxaban 2.5 mg twice daily with aspirin reduced cardiovascular events in COMPASS (stable coronary or peripheral disease) and in VOYAGER PAD (after lower-extremity revascularization). This vascular dose does not prevent stroke in AF, and both trials excluded patients who needed full-dose anticoagulation. It is not combined with a full-dose anticoagulant and is not a substitute for one. Peripheral regimens are covered on the peripheral artery disease page.

Left atrial appendage occlusion. In patients with AF who cannot take long-term anticoagulation, percutaneous left atrial appendage occlusion removes the need for an anticoagulant after the device has healed. The 2023 AF guideline rates it as reasonable in patients with CHA₂DS₂-VASc of 2 or more and a contraindication to long-term anticoagulation from a nonreversible cause (Class 2a, B-NR). It may be reasonable as an alternative in patients at high risk of major bleeding on anticoagulation, based on patient preference and with the understanding that the evidence for anticoagulation is more extensive (Class 2b, B-R).

Occlusion does not remove the need for antiplatelet therapy after coronary stenting, and the post-implant regimen for the device itself often includes antiplatelet agents or a short course of anticoagulation. In a patient with a recent coronary stent, the coronary antiplatelet course determines the regimen once anticoagulation for the device has been completed. Occlusion is therefore most useful in patients with recurrent bleeding on anticoagulation whose stents are more than 12 months old. Device selection and post-implant regimens are covered on the left atrial appendage occlusion page.

Proton pump inhibitor protection and the clopidogrel interaction

The gastrointestinal tract is the most frequent site of serious bleeding during combined anticoagulant and antiplatelet therapy. The 2025 ACS guideline recommends a proton pump inhibitor in patients at high risk of gastrointestinal bleeding who take DAPT, an oral anticoagulant, or both (Class 1, LOE A). The 2020 ACC ECDP recommends starting or continuing a proton pump inhibitor in every patient taking 2 or more antithrombotic agents, with an H2-receptor antagonist in selected cases. Nonsteroidal anti-inflammatory drugs are avoided. The proton pump inhibitor is stopped when the regimen returns to an anticoagulant alone, unless another indication exists.

The clopidogrel interaction. Omeprazole and esomeprazole inhibit CYP2C19 and reduce the conversion of clopidogrel to its active metabolite. The US prescribing information for clopidogrel advises against concomitant use of omeprazole or esomeprazole. In COGENT, the only randomized trial of the interaction, omeprazole reduced gastrointestinal events in patients taking clopidogrel and aspirin without a significant increase in cardiovascular events. Post hoc analyses of other trials have not shown increased ischemic risk with clinically indicated proton pump inhibitors. Pantoprazole, which has less CYP2C19 inhibition, avoids the pharmacokinetic interaction and is the usual choice with clopidogrel. Ticagrelor and prasugrel are not affected.

Gastrointestinal and other bleeding during combination therapy

Bleeding during combination therapy is graded by severity and site. Minor bleeding (bruising, epistaxis controlled by local measures) is managed without stopping any agent, and patients are counseled not to stop their drugs on their own. Clinically relevant bleeding leads to review of the regimen. Aspirin is stopped first if still present. Then the antiplatelet duration is shortened, kidney function and DOAC dose are reassessed, and the bleeding source is investigated and treated.

Major bleeding requires temporary interruption of the anticoagulant, local hemostasis (endoscopic, interventional, or surgical), transfusion when indicated, and reversal for life-threatening bleeding. In the first month after stenting, the P2Y12 inhibitor is continued whenever hemostasis can be achieved, because stopping all antiplatelet therapy early after PCI carries a high risk of stent thrombosis. After hemostasis, the anticoagulant is resumed. Permanent discontinuation of anticoagulation in a patient with AF and a high CHA₂DS₂-VASc score leaves the stroke risk untreated, and left atrial appendage occlusion is an option when the bleeding source cannot be corrected. Reversal agents, timing of resumption, and bleeding by site are covered on the anticoagulant bleeding, reversal, and periprocedural management page.

Special populations: older adults, kidney disease, East Asian patients, and cancer

Older adults and frailty. The mean age in the DOAC trials was about 70 years, and patients aged 75 years or older formed a large minority. The benefit of dual over triple therapy was consistent across age groups, and the absolute bleeding reduction is largest in the oldest patients because their baseline risk is highest. Age alone is not a reason to reduce the DOAC dose; apixaban is reduced only with 2 of its 3 criteria, and edoxaban and rivaroxaban only for kidney function or edoxaban’s weight criterion. Falls, frailty, polypharmacy, and cognitive impairment raise bleeding risk and adherence problems, and they favor the shortest aspirin course and early return to anticoagulant monotherapy.

Chronic kidney disease and dialysis. AUGUSTUS, PIONEER AF-PCI, and RE-DUAL PCI excluded patients with a creatinine clearance below 30 mL/min, so evidence is weakest where bleeding risk is highest. DOAC doses follow the labeled kidney thresholds in the dose table above. Edoxaban is not used with a creatinine clearance above 95 mL/min, and dabigatran is contraindicated below 15 mL/min. In dialysis, apixaban and warfarin are the anticoagulants most often used, without randomized data in the PCI setting. Kidney function often worsens after contrast exposure and ACS, and doses are recalculated before discharge and at follow-up.

East Asian patients. East Asian patients have higher bleeding risk with potent antiplatelet therapy. The evidence for early and chronic anticoagulant monotherapy comes largely from East Asian trials (OAC-ALONE, AFIRE, EPIC-CAD, ADAPT AF-DES, and OPTIMA-AF). AQUATIC, conducted in France, is the main Western confirmation in the chronic phase. The applicability of very short dual therapy to Western patients with ACS is not established.

Cancer. Active cancer within the past 12 months is an ARC-HBR major criterion, and thrombocytopenia from chemotherapy adds further risk. Cancer also raises the risk of VTE and stent thrombosis, and drug interactions between DOACs and cancer therapies are common. Antithrombotic regimens in cancer are individualized with oncology input and are covered on the cancer-associated thrombosis page.

Women. Women formed 20% to 29% of the trial populations and have higher bleeding risk after PCI. Sex is not a criterion for DOAC dose reduction, and the same regimen applies.

Shared decision-making, adherence, and discharge documentation

Patients and clinicians weigh the outcomes differently. In a study of patients with AF and the physicians who treat them, patients placed more value on avoiding stroke and accepted more bleeding than physicians did. Shared decision-making explains the purpose of each drug, the expected duration of each phase, and the reason aspirin stops early even though the stent is new.

Adherence to the anticoagulant is essential because DOACs have short half-lives, and missed doses leave the patient without stroke protection within a day. Patients are told which drug to continue if bleeding occurs and whom to contact before stopping any agent.

The discharge summary records each drug with its dose and planned stop date: the aspirin, P2Y12 inhibitor, and proton pump inhibitor stop dates, with the anticoagulant recorded as indefinite. It also states the indication for each drug, so that later prescribers can see which drug protects the stent and which prevents stroke. Primary care and pharmacy receive the same plan, and follow-up visits at 1 month, 6 months, and 12 months are scheduled around the planned changes.

Errors in antithrombotic therapy after PCI in atrial fibrillation

• Triple therapy continued beyond 30 days because no stop date was written at discharge, or because a later prescriber restarted aspirin after a clinic visit.
• Ticagrelor or prasugrel used as part of triple therapy; prasugrel is avoided with an anticoagulant and ticagrelor is reserved for selected patients on dual therapy.
• DOAC dose reduced empirically because antiplatelet therapy is added, which sacrifices stroke protection. Apixaban 2.5 mg twice daily with only one dose-reduction criterion is a common example.
• Rivaroxaban left at 15 mg after the P2Y12 inhibitor stops, instead of returning to the labeled 20-mg dose in patients with a creatinine clearance above 50 mL/min.
• Edoxaban prescribed to a patient with a creatinine clearance above 95 mL/min, or dabigatran to a patient with a creatinine clearance below 15 mL/min.
• The AF combination dose of rivaroxaban (15 mg) used for VTE, in which the treatment dose is 20 mg.
• A DOAC used after PCI in a patient with a mechanical heart valve.
• Anticoagulation withheld after PCI in a patient who meets the stroke-risk threshold, on the reasoning that DAPT covers AF. DAPT is inferior to anticoagulation for stroke prevention.
• Aspirin continued with the anticoagulant indefinitely after the first year in stable patients, against the 2023 AF guideline recommendation and the results of AFIRE and AQUATIC.
• All antithrombotic drugs stopped together for minor bleeding in the first month after stenting.
• Omeprazole or esomeprazole prescribed with clopidogrel when pantoprazole avoids the interaction, or the proton pump inhibitor continued indefinitely after the regimen returns to anticoagulant monotherapy.
• Elective PCI performed during the first 3 months of a time-limited VTE course, which forces combination therapy that a short delay would have avoided.

Prognosis and outcomes on contemporary regimens

Patients with AF who undergo PCI have higher mortality than patients without AF, driven by age, comorbidity, heart failure, and bleeding as well as by coronary events. In AUGUSTUS, death or hospitalization within 6 months occurred in about one in four patients. The shift to DOAC-based dual therapy has roughly halved clinically relevant bleeding compared with warfarin triple therapy. It has also reduced intracranial hemorrhage, at the cost of a small absolute increase in early stent thrombosis. In the chronic phase, anticoagulant monotherapy reduces bleeding further, and in AFIRE and AQUATIC it was associated with lower mortality than continued antiplatelet therapy. The remaining questions are the shortest safe antiplatelet course after ACS and the management of patients with prior stent thrombosis or very complex PCI, who were excluded from most trials.

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