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Dual antiplatelet therapy: duration, de-escalation, and bleeding risk

Dual antiplatelet therapy after acute coronary syndromes and coronary stenting: default duration, extension, shortening, P2Y12 inhibitor monotherapy, de-escalation, bleeding definitions and risk scores, surgery, and gastrointestinal protection.

Terms used for shortening, extending, and de-escalating DAPT

The terms below differ in meaning and are not interchangeable. The definitions follow the 2025 ACC/AHA ACS guideline, the 2023 AHA/ACC chronic coronary disease guideline, and the trial literature.

Terms for antiplatelet strategies.

The PARIS registry (5,018 patients after PCI in the United States and Europe) quantified the risk of three modes of stopping DAPT: physician-guided discontinuation, brief interruption (usually for surgery), and disruption (nonadherence or bleeding). Over 2 years, 57.3% of patients stopped DAPT at some point. Compared with continued DAPT, physician-guided discontinuation was associated with lower risk of major adverse cardiac events (hazard ratio 0.63), brief interruption was not significantly associated with risk (hazard ratio 1.41), and disruption was associated with higher risk (hazard ratio 1.50), concentrated in the first 7 days after disruption (hazard ratio 7.04). Most events (74%) occurred while patients were taking DAPT. In the registry, the ischemic consequence depended on the mode of stopping and not on stopping itself.

Duration of DAPT by presentation and bleeding risk: US recommendations

The table assembles the recommendations of the 2025 ACC/AHA ACS guideline, the 2023 AHA/ACC chronic coronary disease guideline, and the 2016 ACC/AHA DAPT focused update for patients without an indication for oral anticoagulation. The 2025 and 2023 documents supersede the 2016 update where they overlap. The 2016 recommendations remain the most specific US statements for several scenarios (bare-metal stents, coronary artery bypass grafting [CABG] in stable disease, and noncardiac surgery timing) and are marked as such.

US recommendations for DAPT duration, with Class of Recommendation and Level of Evidence. Unlabeled classes in ACS rows are from the 2025 ACC/AHA ACS guideline (Section 11.1 and Section 4.3.2); “2023” denotes the AHA/ACC chronic coronary disease guideline (Section 4.3.1); “2016 update” denotes the ACC/AHA DAPT focused update. A proton pump inhibitor is recommended with DAPT in patients at high risk of gastrointestinal bleeding (2025, Class 1, A).

The table is applied at three points in time: at PCI or discharge, when bleeding risk and the anatomic result are known and a planned duration is set; at 1 to 3 months, when aspirin withdrawal or de-escalation becomes possible; and at the end of the default course, when the choice is between single antiplatelet therapy and extension. Each reassessment records bleeding events, new indications for anticoagulation, planned surgery, adherence, and side effects.

Why two antiplatelet drugs: platelet pathways, stent thrombosis, and recurrent ACS

Arterial thrombosis after plaque rupture or erosion and on a freshly implanted stent is platelet-rich. Platelets adhere to exposed collagen and von Willebrand factor, become activated, and amplify their own activation through thromboxane A2 and adenosine diphosphate (ADP) released from dense granules. Aspirin irreversibly acetylates cyclooxygenase-1 (COX-1) and suppresses thromboxane A2 for the life of the platelet. P2Y12 inhibitors block the ADP receptor that sustains activation of the glycoprotein IIb/IIIa receptor and stabilizes the aggregate. Because the two pathways are parallel and mutually reinforcing, combined blockade inhibits aggregation more than either drug alone, and it increases bleeding for the same reason.

DAPT has two distinct targets. The first is the stent: until the struts are covered by neointima, the metal and polymer surface is thrombogenic, and stent thrombosis presents as abrupt vessel closure, most often as ST-elevation myocardial infarction (STEMI), with high mortality. The second is the patient: ACS reflects a systemic prothrombotic and inflammatory state, and a large share of recurrent events after ACS arise from nonculprit plaques, not from the treated segment. This distinction explains why DAPT benefits medically managed ACS (CURE, PLATO) and why extended DAPT after MI reduces spontaneous MI more than stent thrombosis.

The randomized basis for DAPT after ACS is three trials, all of which treated for up to 12 to 15 months:

• CURE (12,562 patients with non-ST-elevation ACS [NSTE-ACS], most managed medically): clopidogrel added to aspirin reduced cardiovascular death, MI, or stroke (9.3% versus 11.4%; relative risk 0.80), with more major bleeding (3.7% versus 2.7%). The benefit appeared within the first day and continued through 12 months.
• TRITON-TIMI 38 (13,608 patients with ACS undergoing PCI): prasugrel reduced cardiovascular death, MI, or stroke compared with clopidogrel (9.9% versus 12.1%; hazard ratio 0.81) and stent thrombosis (1.1% versus 2.4%), with more major bleeding (2.4% versus 1.8%) and fatal bleeding (0.4% versus 0.1%).
• PLATO (18,624 patients with ACS, invasive or medical management): ticagrelor reduced vascular death, MI, or stroke (9.8% versus 11.7%; hazard ratio 0.84) and all-cause death (4.5% versus 5.9%). Total major bleeding did not differ (11.6% versus 11.2%), but major bleeding unrelated to CABG was more frequent (4.5% versus 3.8%).

Stent design changed the balance between these two targets. First-generation drug-eluting stents (sirolimus and paclitaxel, with durable polymers and thick struts) delayed healing and carried a measurable risk of very late stent thrombosis, which drove the original recommendation for at least 12 months of DAPT after any drug-eluting stent. Thin-strut, newer-generation stents with biocompatible, biodegradable, or no polymer heal faster and have lower rates of stent thrombosis. That change allowed trials of 1 to 6 months of DAPT and ended the practice of choosing a bare-metal stent to permit short DAPT: in LEADERS FREE, a polymer-free drug-coated stent with 1 month of DAPT was superior to a bare-metal stent in high-bleeding-risk patients. Stent thrombosis definitions, timing, and mechanisms are covered in Stent thrombosis and in-stent restenosis; stent platforms and technique, in Percutaneous coronary intervention: equipment, stents and technique.

Choice of P2Y12 inhibitor and how it bears on duration

The individual agents, their pharmacology, loading regimens, and interactions are covered in Antiplatelet therapy: aspirin, P2Y12 inhibitors and glycoprotein IIb/IIIa inhibitors.

Oral P2Y12 inhibitors and aspirin as they bear on DAPT duration. Doses from the 2025 ACC/AHA ACS guideline (Table 7).

Prasugrel limits. In TRITON-TIMI 38, patients with prior stroke or transient ischemic attack had net harm with prasugrel, including more intracranial hemorrhage, and patients 75 years or older or weighing less than 60 kg had no net benefit at the 10-mg dose. The US label therefore contraindicates prasugrel after stroke or transient ischemic attack, generally avoids it at 75 years or older except in high-risk situations such as diabetes or prior MI, and advises considering a 5-mg maintenance dose below 60 kg. These limits matter for duration because older and lighter patients are also those in whom bleeding drives the decision to shorten or de-escalate.

Aspirin dose with ticagrelor. In PLATO, the effect of ticagrelor was attenuated in North America, where many patients took 300 mg or more of aspirin daily; analyses attributed much of the regional interaction to aspirin dose. The 2025 ACC/AHA guideline states that aspirin doses of 100 mg daily or less are always used with ticagrelor.

CYP2C19 and clopidogrel. Loss-of-function alleles (principally 2 and 3) reduce formation of the active metabolite of clopidogrel. They are carried by about 30% of people of European and African ancestry and by a higher proportion of East Asian people. Carriers have less platelet inhibition and more ischemic events after PCI. Response variability is the reason clopidogrel monotherapy started 1 to 2 months after ACS raised concern for excess events (STOPDAPT-2 ACS) and the rationale for genotype-guided de-escalation (described below).

Choice in STEMI and NSTE-ACS. In STEMI treated with primary PCI, prasugrel or ticagrelor is given (Class 1, B-R), and clopidogrel is used when they are unavailable, not tolerated, or contraindicated (Class 1, C-LD). In NSTE-ACS undergoing PCI, prasugrel or ticagrelor is recommended (Class 1, B-R); in medically managed NSTE-ACS, ticagrelor is recommended (Class 1, B-R). After fibrinolysis, clopidogrel is the P2Y12 inhibitor (Class 1, A), given as 300 mg at age 75 years or younger and as 75 mg without a loading dose above 75 years. The comparison of ticagrelor and prasugrel in ISAR-REACT 5 and the details of pretreatment are covered in Non-ST-elevation acute coronary syndrome and ST-elevation myocardial infarction.

The time course of ischemic and bleeding risk after PCI and ACS

Ischemic risk after ACS or PCI is highest in the first 30 days, when acute and subacute stent thrombosis and early recurrent infarction occur. It then declines over the following months to a lower, persistent rate driven mainly by spontaneous events at nonculprit sites. Bleeding risk on DAPT is also front-loaded, with access-site and gastrointestinal bleeding concentrated in the first weeks. It then accumulates at a roughly constant rate for as long as two antiplatelet drugs are given. Most of the ischemic benefit of the second drug therefore accrues early, and most of its cumulative bleeding cost accrues late. Each strategy below exploits this asymmetry: shortening and aspirin withdrawal remove the late bleeding cost; extension buys additional reduction of spontaneous MI at that cost; de-escalation lowers intensity once the early hazard has passed.

Major bleeding after PCI is associated with subsequent mortality of a magnitude similar to that of recurrent MI, and the ARC-HBR consensus based its threshold on this association, because type 3 or 5 bleeding on the Bleeding Academic Research Consortium (BARC) scale is prognostically important. The mechanisms linking bleeding to death include the bleed itself, anemia and transfusion, and premature cessation of all antiplatelet therapy with subsequent thrombosis. The association is not proof that every bleed causes death, because the patients who bleed are older and sicker, but it is the reason bleeding reduction became a primary end point of DAPT trials.

Bleeding definitions: BARC, TIMI, GUSTO, and ISTH

Trials of DAPT duration report bleeding by different scales, and a trial's apparent bleeding reduction depends on which scale is used. The BARC definition, published in 2011, unified earlier scales into a hierarchical classification and is the standard in contemporary PCI trials and in the ARC-HBR definition.

Bleeding Academic Research Consortium classification (Mehran et al., Circulation 2011). Trials commonly report “clinically relevant bleeding” as BARC 2, 3, or 5 and “major bleeding” as BARC 3 or 5. A hemoglobin drop is corrected for transfusion (1 unit of packed red cells or whole blood is assumed to raise hemoglobin by 1 g/dL).

Bleeding scales used in DAPT trials. Laboratory-based scales (TIMI) count fewer events than clinical scales that include actionable bleeding (BARC 2, ISTH clinically relevant nonmajor), so absolute bleeding rates are not compared across trials that used different definitions.

Defining high bleeding risk: ARC-HBR criteria

The Academic Research Consortium for High Bleeding Risk, a group that included representatives of the US Food and Drug Administration and the Japanese regulatory agency, published a consensus definition in 2019. A patient is at high bleeding risk when at least 1 major or 2 minor criteria are present at the time of PCI. A major criterion is a factor that by itself carries a 1-year risk of BARC 3 or 5 bleeding of 4% or more or of intracranial hemorrhage of 1% or more; a minor criterion raises risk without reaching that threshold. The 2025 ACC/AHA ACS guideline reproduces the criteria (Table 22) as its definition of high bleeding risk.

Academic Research Consortium high bleeding risk criteria after PCI (Urban et al., Circulation 2019), as reproduced in the 2025 ACC/AHA ACS guideline (Table 22). Active malignancy means diagnosis within 12 months or ongoing treatment, including surgery, chemotherapy, or radiotherapy.

High bleeding risk is present with at least 1 major or 2 minor criteria. The checklist identifies high bleeding risk as a category; the PRECISE-DAPT score below estimates it on a continuous scale.

The ARC-HBR definition has been validated in registries, in which patients meeting it had BARC 3 or 5 bleeding rates at or above the 4% threshold, and in which risk rose with the number of criteria. The definition is binary at the threshold, so a patient with 1 major criterion and a patient with 5 are both “high bleeding risk.” Several criteria are also ischemic risk factors (age, kidney disease, anemia, prior stroke), so most patients at high bleeding risk are also at elevated ischemic risk, and in MASTER DAPT and XIENCE short-DAPT studies their rates of death or MI were high on any regimen. Anticipated long-term oral anticoagulation is a major criterion; for those patients the antiplatelet plan follows the anticoagulation evidence. Finally, bleeding risk is partly modifiable: radial access, proton pump inhibitor use, avoidance of NSAIDs, blood pressure control, correct dosing of anticoagulants, and treatment of anemia lower the risk that the criteria estimate.

Risk scores for bleeding and ischemia on DAPT

PRECISE-DAPT: bleeding risk at the time of PCI. The PRECISE-DAPT score was derived from 14,963 patients treated with DAPT after coronary stenting in eight randomized trials, most of whom received aspirin and clopidogrel and none of whom took an oral anticoagulant. It predicts out-of-hospital TIMI major or minor bleeding from five variables: age, creatinine clearance, hemoglobin, white-cell count, and prior spontaneous bleeding. Its c-statistic was 0.73 in the derivation cohort, 0.70 in the PLATO validation cohort (8,595 patients treated with PCI), and 0.66 in the BernPCI registry (6,172 patients). Scores of 10 or less, 11 to 17, 18 to 24, and 25 or more classify bleeding risk as very low, low, moderate, and high.

The score was evaluated in an analysis of the 10,081 patients randomized to long (12 to 24 months) or short (3 to 6 months) DAPT. In patients with a score of 25 or more, long DAPT increased bleeding (number needed to harm 38) without reducing ischemic events. In patients with a score below 25, long DAPT did not significantly increase bleeding and reduced the composite of MI, definite stent thrombosis, stroke, and target-vessel revascularization (number needed to treat 65). The interaction for bleeding was significant (P = 0.007). The score answers one question: at the time of PCI, whether a short course is preferable to a standard one.

The PRECISE-DAPT nomogram expressed as an equation. Each input is truncated to the nomogram range: age 50 to 90 years (0 to 19 points), creatinine clearance 100 to 0 mL/min (0 to 25 points), hemoglobin 12 to 10 g/dL (0 to 15 points), and white-cell count 5 to 20 × 10⁹/L (0 to 15 points); prior spontaneous bleeding adds 26 points. When weight, serum creatinine, and sex are entered, the Cockcroft-Gault clearance replaces the entered clearance: (140 − age) × weight ÷ (72 × creatinine), × 0.85 in women.

Two input errors misclassify risk. Creatinine clearance in the score is the Cockcroft-Gault estimate, and substituting an eGFR from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation overestimates kidney function in older patients of low body weight. Prior spontaneous bleeding means bleeding that required medical attention and was not related to trauma or a procedure (gastrointestinal bleeding, hematuria, hemoptysis); access-site and postprocedural bleeding do not qualify, and counting them inflates the score by 26 points.

DAPT score: whether to extend beyond 12 months. The DAPT score was derived from 11,648 patients in the DAPT Study and validated in 8,136 patients of the PROTECT trial. It assigns 1 point each for MI at presentation, prior MI or PCI, diabetes, stent diameter below 3 mm, cigarette smoking, and paclitaxel-eluting stent. It assigns 2 points each for heart failure or left ventricular ejection fraction (LVEF) below 30% and for vein graft PCI. Age subtracts points: −1 for age 65 to 74 years and −2 for age 75 years or older. The range is −2 to 10. It is applied only at 12 months, to patients who completed 12 months of DAPT without a major ischemic or bleeding event, the population of the DAPT Study.

In the high-score group (2 or more; 5,917 patients), continued thienopyridine (clopidogrel or prasugrel) reduced MI or stent thrombosis from 5.7% to 2.7% (risk difference −3.0%) with a nonsignificant increase in moderate or severe bleeding (1.8% versus 1.4%). In the low-score group (below 2; 5,731 patients), the ischemic reduction was small and nonsignificant (1.7% versus 2.3%) and bleeding increased significantly (3.0% versus 1.4%). The c-statistics were 0.70 for ischemia and 0.68 for bleeding in derivation and 0.64 for both in PROTECT. The score's components reflect its derivation era: paclitaxel-eluting stents are no longer implanted, and the age terms combine an ischemic and a bleeding effect into one negative weight.

Event rates are continued thienopyridine versus placebo between 12 and 30 months in the DAPT Study. MI at presentation and prior MI or PCI are separate items, and a patient with non-ST-elevation myocardial infarction (NSTEMI) and a prior MI receives both points. Heart failure counts only as a clinical diagnosis or a documented LVEF below 30%.

Using the two scores together. The scores address sequential, nonoverlapping decisions and were derived in different populations with different end points. PRECISE-DAPT is applied at PCI and asks whether to shorten; the DAPT score is applied at 12 months and asks whether to extend. A low PRECISE-DAPT score and a DAPT score below 2 support the default duration without extension. A low PRECISE-DAPT score and a DAPT score of 2 or more define the patient in whom extension is best supported, with ticagrelor 60 mg twice daily after MI or with continued clopidogrel. A high PRECISE-DAPT score at PCI places the patient outside the population in which the DAPT score was derived, since that population was selected for having completed 12 months without bleeding.

Neither score captures the P2Y12 inhibitor used, the anatomic complexity of the stented segment, or anticoagulation. The US and European documents weigh the following features of high thrombotic risk separately from either score:

Ischemic risk features not captured by the DAPT and PRECISE-DAPT scores. The procedural features constitute the complex-PCI definition used in pooled analyses of DAPT duration trials.

PRECISE-HBR and other bleeding scores. The PRECISE-HBR score extends the PRECISE-DAPT approach to the ARC-HBR era, incorporating oral anticoagulation and other ARC-HBR elements, and grades bleeding risk continuously within the high-risk group. In 3,364 high-bleeding-risk patients from the XIENCE short-DAPT program, scores of 22 or less, 23 to 26, and 27 or more were associated with BARC 3 to 5 bleeding rates of 0.3%, 2.5%, and 5.6%, and with death or MI rates of 2.9%, 4.6%, and 9.8%. One month of DAPT reduced BARC 3 to 5 bleeding compared with 3 months only in patients with a score of 27 or more (hazard ratio 0.59), with similar ischemic risk at all levels. The score has not been adopted by US guidelines. Other instruments include the PARIS bleeding and thrombotic scores (registry-derived) and the CRUSADE score for in-hospital bleeding in NSTEMI (described in Non-ST-elevation acute coronary syndrome). In patients taking anticoagulants, HAS-BLED is used (described in Atrial fibrillation). All have modest discrimination, with c-statistics generally between 0.6 and 0.75, which is why US guidelines use them to inform and not to dictate duration.

Default duration after ACS: 12 months and its evidence

In patients with ACS who are not at high bleeding risk, DAPT with aspirin and an oral P2Y12 inhibitor is administered for at least 12 months to reduce major adverse cardiovascular events (2025 ACC/AHA, Class 1, A). The recommendation applies whether the patient is treated with PCI, CABG, or medical therapy. Its basis is the 12- to 15-month treatment period of CURE, TRITON-TIMI 38, and PLATO, and the sustained prothrombotic state that follows ACS. The guideline notes that patients at elevated bleeding risk were typically excluded from these trials, so the 12-month default applies to patients without high bleeding risk, and that the choice of P2Y12 inhibitor varies with treatment approach.

Trials that randomized ACS patients to 6 months of DAPT followed by aspirin alone have not supported shortening by stopping the P2Y12 inhibitor. In SMART-DATE (2,712 patients with ACS, 38% STEMI, mostly treated with clopidogrel), 6 months of DAPT was noninferior to 12 months or longer for the composite of death, MI, or stroke (4.7% versus 4.2%) by a 2.0% margin. However, MI was more frequent with 6 months (1.8% versus 0.8%; hazard ratio 2.41), and BARC 2 to 5 bleeding was not significantly reduced (2.7% versus 3.9%). The 2025 ACC/AHA guideline cites this trial as evidence of excess thrombotic risk when the P2Y12 inhibitor is discontinued and aspirin continued after ACS. The ACS subgroup of ISAR-SAFE (6 versus 12 months of clopidogrel) found no difference, but the trial was stopped early for low event rates and slow recruitment.

The current evidence therefore separates two kinds of shortening after ACS. Stopping the P2Y12 inhibitor and continuing aspirin early after ACS removes the more potent drug at the time it is most effective and has produced ischemic signals. Stopping aspirin and continuing a potent P2Y12 inhibitor (ticagrelor) has reduced bleeding without an ischemic signal and holds a Class 1 recommendation. In both cases the total duration of antiplatelet therapy is lifelong; what changes is whether one drug or two are given.

STEMI patients are part of the ACS evidence and receive the same 12-month default. In TICO, 36% of patients had STEMI, and an analysis by presentation showed consistent effects of ticagrelor monotherapy after 3 months across STEMI, NSTEMI, and unstable angina, without evidence of more ischemic events in STEMI. Patients with STEMI were 40% of T-PASS. The European and US guidelines nevertheless list STEMI among features that argue for caution with very early aspirin withdrawal, and the trial that withdrew aspirin immediately after PCI (NEO-MINDSET) enrolled mainly patients with ACS and showed more stent thrombosis.

Default duration after PCI for chronic coronary disease: 6 months

In patients with chronic coronary disease treated with PCI, DAPT consisting of aspirin and clopidogrel for 6 months after PCI, followed by single antiplatelet therapy, is indicated to reduce major adverse cardiovascular events and bleeding (2023 AHA/ACC, Class 1). The 2016 focused update set the same minimum (clopidogrel for at least 6 months after a drug-eluting stent, Class 1, B-R; at least 1 month after a bare-metal stent, Class 1, A) and allowed discontinuation after 3 months in patients at high bleeding risk or with overt bleeding (Class 2b, C-LD). Clopidogrel is the P2Y12 inhibitor after elective PCI because prasugrel and ticagrelor have not improved outcomes in this setting and increase bleeding.

The 6-month default rests on randomized trials that compared 3 or 6 months with 12 months or longer after newer-generation drug-eluting stents in mixed populations, most with stable disease. These trials (EXCELLENT, RESET, OPTIMIZE, SECURITY, ISAR-SAFE, ITALIC, and others) found shorter DAPT noninferior for ischemic composites, with less bleeding in some. PRODIGY (2,013 all-comers randomized at 30 days to 6 or 24 months of clopidogrel) found no difference in death, MI, or stroke at 2 years (10.0% versus 10.1%; hazard ratio 0.98) and more bleeding with 24 months by every definition.

In selected patients with a drug-eluting stent who have completed 1 to 3 months of DAPT, P2Y12 inhibitor monotherapy for at least 12 months is reasonable to reduce bleeding risk (2023 AHA/ACC, Class 2a). The trials underpinning this option (TWILIGHT, SMART-CHOICE, STOPDAPT-2, GLOBAL LEADERS) enrolled both stable and ACS patients and are described below. The 2024 ESC chronic coronary syndrome guideline retains 6 months of aspirin and clopidogrel as the default and recommends stopping DAPT after 1 to 3 months in patients at high bleeding risk who are not at high ischemic risk (Class I).

Extended DAPT beyond 12 months

Extension targets the persistent risk of spontaneous MI after ACS and in diffuse coronary disease. It requires that the patient tolerated DAPT without bleeding, and the absolute benefit is modest.

Randomized evidence on extended DAPT. HR, hazard ratio; MACCE, major adverse cardiovascular and cerebrovascular events. The DAPT Study observed a rise in stent thrombosis and MI in both groups in the 3 months after thienopyridine was stopped.

The DAPT Study reduced both stent-related and spontaneous MI, and more than half of the MI reduction was unrelated to stent thrombosis, consistent with protection of the whole coronary tree. The increase in all-cause mortality was borderline significant and was driven by noncardiovascular deaths, including cancer deaths in patients whose cancer was diagnosed before enrollment. Meta-analyses differ on mortality: the network meta-analysis above found higher all-cause mortality with longer DAPT, driven by noncardiac death, whereas other pooled analyses found no significant difference. Together, these results frame extension as a trade between fewer MIs and more bleeding with uncertain effect on survival.

PEGASUS-TIMI 54 enrolled patients 1 to 3 years after MI who were 50 years or older and had at least 1 of the following: age 65 years or older, diabetes requiring medication, a second prior MI, multivessel coronary disease, or chronic kidney disease. Both doses reduced the primary end point, and the 60-mg dose had fewer adverse effects (bleeding and dyspnea) and is the approved dose for extension. The benefit was greater when ticagrelor was started within 2 years of the MI or within 1 year of stopping a previous P2Y12 inhibitor than after a longer gap.

In THEMIS (19,220 patients with diabetes and stable coronary disease without prior MI or stroke), ticagrelor added to aspirin reduced ischemic events but increased TIMI major bleeding and intracranial hemorrhage, with no net benefit in the overall trial. The subgroup with prior PCI (THEMIS-PCI) had a net clinical benefit. Since 2020, the US label has included ticagrelor 60 mg twice daily to reduce the risk of a first MI or stroke in patients with coronary artery disease at high risk for such events. Efficacy was established in the THEMIS population with type 2 diabetes. The increase in major and intracranial bleeding confines its use to patients at low bleeding risk.

US recommendations. The 2016 focused update states that in patients with ACS treated with DAPT who have tolerated it without bleeding complications and are not at high bleeding risk, continuation beyond 12 months may be reasonable (Class 2b, A); the same applies after PCI for stable disease beyond 6 months. The 2023 AHA/ACC guideline states that in patients with chronic coronary disease who have had a previous MI and are at low bleeding risk, extended DAPT beyond 12 months for up to 3 years may be reasonable to reduce major adverse cardiovascular events (Class 2b, A). The 2025 ACC/AHA ACS guideline notes that in select patients who have tolerated DAPT it may be reasonable to extend treatment beyond 12 months after considering the risks of long-term bleeding and thrombosis.

Dual-pathway inhibition. In COMPASS (27,395 patients with stable coronary or peripheral artery disease), rivaroxaban 2.5 mg twice daily plus aspirin reduced cardiovascular death, stroke, or MI compared with aspirin alone (4.1% versus 5.4%; hazard ratio 0.76) and reduced all-cause death (3.4% versus 4.1%), with more major bleeding (3.1% versus 1.9%) but no significant increase in intracranial or fatal bleeding. The 2023 AHA/ACC guideline rates the combination as reasonable in patients with chronic coronary disease at high ischemic and low or moderate bleeding risk who have no indication for anticoagulation or DAPT (Class 2a). It is an alternative long-term strategy to extended DAPT, not an extension of it, and the two are not combined. Details are in Chronic coronary disease and Peripheral artery disease.

Vorapaxar and cilostazol. Vorapaxar, a protease-activated receptor-1 antagonist, reduced ischemic events when added to standard antiplatelet therapy in patients with prior MI or peripheral artery disease but increased intracranial hemorrhage; it is contraindicated after stroke, transient ischemic attack, or intracranial hemorrhage (2023 AHA/ACC, Class 3: Harm) and is rarely used. Cilostazol, a phosphodiesterase-3 inhibitor, has been added to DAPT (“triple antiplatelet therapy”) in East Asian trials but is not part of US recommendations for coronary stenting; its labeled indication is claudication, and it is contraindicated in heart failure.

Short DAPT followed by P2Y12 inhibitor monotherapy

Aspirin withdrawal tests whether the P2Y12 inhibitor alone carries most of the antithrombotic benefit after the first weeks. Pharmacodynamic studies show that with a potent P2Y12 inhibitor, adding aspirin contributes little further inhibition of ADP-mediated aggregation, while aspirin remains responsible for much of the mucosal and gastrointestinal bleeding.

Randomized trials of P2Y12 inhibitor monotherapy after short or no DAPT. Most enrolled patients at low to intermediate ischemic risk and excluded those with recent stent thrombosis, and the Korean and Japanese trials were open label. HR, hazard ratio; MACCE, major adverse cardiac and cerebrovascular events.

Ticagrelor monotherapy begun 1 to 3 months after PCI, after a period of ticagrelor-based DAPT, reduced bleeding by roughly half without an increase in ischemic events. In the blinded trials (TWILIGHT and ULTIMATE-DAPT), the bleeding reduction is not attributable to open-label ascertainment. A patient-level meta-analysis of TICO and T-PASS (5,906 ACS patients) found ischemic events of 1.9% versus 2.5% (hazard ratio 0.79, not significant) and bleeding of 2.4% versus 4.5% (hazard ratio 0.54). GLOBAL LEADERS did not show superiority of the ticagrelor-monotherapy strategy for its hard primary end point, and adherence to ticagrelor fell over the second year.

Clopidogrel monotherapy produced a different result in ACS. In STOPDAPT-2 ACS, clopidogrel alone from 1 to 2 months failed noninferiority and was associated with numerically more cardiovascular events, mainly MI. A patient-level meta-analysis of six trials (25,960 patients) found ticagrelor monotherapy noninferior to DAPT for death, MI, or stroke (hazard ratio 0.89), whereas clopidogrel monotherapy did not meet noninferiority (hazard ratio 1.37, driven by noncardiovascular death). Major bleeding was lower with both (hazard ratios 0.47 and 0.49), and net adverse clinical events were lower with ticagrelor (hazard ratio 0.74) but not with clopidogrel. All clopidogrel-monotherapy trials were conducted in East Asia, where CYP2C19 loss-of-function alleles are common and where ischemic event rates and bleeding responses differ from Western populations.

Removal of aspirin at or immediately after PCI has not been shown to be safe. In STOPDAPT-3, aspirin-free low-dose prasugrel did not reduce major bleeding in the first month and was associated with more subacute stent thrombosis and unplanned revascularization. In NEO-MINDSET, immediate potent P2Y12 inhibitor monotherapy failed noninferiority for ischemic events while reducing bleeding. The evidence supports aspirin for at least the first weeks after PCI, with the strongest data for withdrawal at 1 to 3 months.

US recommendations. In patients with ACS who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy 1 month or more after PCI is useful to reduce bleeding risk (2025 ACC/AHA, Class 1, A). The guideline notes concern that clopidogrel monotherapy started 1 to 2 months after PCI may increase major adverse cardiovascular events in ACS compared with longer DAPT, possibly because of inadequate platelet inhibition in the 30% to 40% of patients with high on-treatment reactivity after PCI. It also notes that prasugrel monotherapy has not been established after ACS (low-dose prasugrel monotherapy very early after PCI in Japanese patients may increase 30-day events). In chronic coronary disease, P2Y12 inhibitor monotherapy for at least 12 months after 1 to 3 months of DAPT with a drug-eluting stent is reasonable (2023 AHA/ACC, Class 2a).

Very short DAPT in patients at high bleeding risk

Patients at high bleeding risk were excluded from the trials that defined standard durations and were studied in a separate series of trials, most of which paired 1 month of DAPT with a specific stent.

Randomized and registry evidence for 1-month DAPT in high bleeding risk. In MASTER DAPT, clinicians chose which antiplatelet drug to continue, and clopidogrel was continued in 53.9% of the abbreviated group. HR, hazard ratio; MACCE, major adverse cardiac or cerebral events.

MASTER DAPT is the trial behind the US recommendation. It was not designed to determine whether aspirin or the P2Y12 inhibitor should be continued, and among ACS patients a potent P2Y12 inhibitor was chosen in about one quarter. Results in the ACS cohort were consistent with the overall trial. The 2025 ACC/AHA ACS guideline therefore states that in patients with ACS undergoing PCI who are at high bleeding risk, transition to single antiplatelet therapy (aspirin or a P2Y12 inhibitor) after 1 month may be reasonable to reduce bleeding risk (Class 2b, B-R). The 2016 focused update allowed discontinuation of the P2Y12 inhibitor after 6 months in ACS and after 3 months in stable disease in patients at high bleeding risk or with significant overt bleeding (Class 2b, C-LD); the 2025 and 2023 documents shorten those intervals.

In high-bleeding-risk patients who tolerated ticagrelor-based DAPT, ticagrelor monotherapy from 1 month carries the Class 1 recommendation as well. Many high-bleeding-risk patients, however, are older patients for whom clopidogrel is the P2Y12 inhibitor of choice, and for them the choice after 1 month is between clopidogrel alone and aspirin alone.

De-escalation from prasugrel or ticagrelor to clopidogrel

De-escalation keeps DAPT but lowers its intensity after the early high-risk period. In practice, many patients are switched from ticagrelor to clopidogrel because of bleeding, dyspnea, or cost.

Randomized trials of de-escalation and guided P2Y12 inhibitor selection. TAILOR-PCI tested escalation in carriers; the others tested de-escalation from a potent agent. HR, hazard ratio.

Unguided switching at 1 month reduced bleeding in TOPIC and TALOS-AMI. Guided de-escalation by platelet function testing (TROPICAL-ACS) or genotype (POPular Genetics) was noninferior to continued potent therapy for net clinical outcomes, with less minor bleeding in POPular Genetics. Pooled analyses of guided and unguided de-escalation show ischemic efficacy comparable with standard DAPT and less bleeding. Against these results stand TRITON-TIMI 38 and PLATO, in which the advantage of the potent agent over clopidogrel continued to accrue beyond the first month.

US recommendations. In patients with ACS undergoing PCI, de-escalation of DAPT (switching from ticagrelor or prasugrel to clopidogrel) after 1 month may be reasonable to reduce bleeding risk (2025 ACC/AHA, Class 2b, B-R). The guideline describes both guided and unguided approaches without preferring one. The 2023 ESC guideline also lists de-escalation as an alternative strategy (Class IIb) and recommends against de-escalation in the first 30 days after ACS. Routine platelet function testing has not improved outcomes in unselected PCI populations, and universal genotyping is not recommended by US guidelines; testing is used when its result changes P2Y12 inhibitor selection.

Switching between P2Y12 inhibitors: loading doses and timing

Switching is frequent, and the pharmacology of each pair determines whether a loading dose is needed and when it is given. Transitions from a reversible agent (ticagrelor) to an irreversible thienopyridine create a window in which the active metabolite of the thienopyridine cannot bind receptors still occupied by ticagrelor. A loading dose given 24 hours after the last ticagrelor dose avoids a gap in inhibition. The International Expert Consensus on switching (2017) proposed the following regimens.

Switching regimens from the International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies (Angiolillo et al., Circulation 2017). When de-escalation is prompted by bleeding, the switch from ticagrelor to clopidogrel can be made without a loading dose (75 mg daily, 24 hours after the last ticagrelor dose). Transitions between cangrelor and oral agents are given in the 2025 ACC/AHA guideline (Table 9).

Aspirin dose and the long-term single antiplatelet drug

Aspirin dose. The 2016 focused update recommends 81 mg (range 75 to 100 mg) daily in patients treated with DAPT (Class 1, B-NR). The comparison of 81 mg and 325 mg in patients with atherosclerotic disease (ADAPTABLE) is described in Chronic coronary disease.

Aspirin or clopidogrel after DAPT ends. Aspirin has been the default long-term single antiplatelet drug since the antiplatelet trialists' meta-analyses, but randomized evidence now supports clopidogrel as an alternative. In HOST-EXAM (5,438 Korean patients who completed DAPT without events 6 to 18 months after PCI), clopidogrel 75 mg reduced the composite of death, MI, stroke, readmission for ACS, or BARC 3 or greater bleeding compared with aspirin 100 mg over 24 months (5.7% versus 7.7%; hazard ratio 0.73). The thrombotic and bleeding components were both lower. The extended follow-up to a median of 10.5 years maintained the difference in the composite without a difference in all-cause mortality. SMART-CHOICE 3 (5,506 Korean patients at high ischemic risk, randomized a median of 17.5 months after PCI) found fewer events with clopidogrel (3-year incidence 4.4% versus 6.6%; hazard ratio 0.71), with fewer MIs and identical bleeding (3.0% in both groups). A 2025 patient-level meta-analysis of seven trials (28,982 patients) found fewer major adverse cardiovascular and cerebrovascular events with clopidogrel than with aspirin, without differences in major bleeding or mortality.

US guidelines continue to recommend aspirin 75 to 100 mg daily as long-term therapy in chronic coronary disease, with clopidogrel 75 mg as the alternative in patients who cannot take aspirin. The 2024 ESC guideline gives clopidogrel 75 mg daily a Class I recommendation as a safe and effective alternative to aspirin monotherapy in patients with prior PCI or MI. The long-term trials were conducted mainly in East Asia.

Aspirin monotherapy after short DAPT. Stopping the P2Y12 inhibitor after short DAPT and continuing aspirin was tested in One-Month DAPT (noninferior after noncomplex PCI with a polymer-free stent) and in SMART-DATE after ACS (more MI with 6 months of DAPT). The 2025 ACC/AHA guideline describes aspirin monotherapy after 3 or 6 months of DAPT in ACS as associated with excess thrombotic risk and does not recommend it outside high bleeding risk.

DAPT after CABG and P2Y12 interruption before surgery

ACS patients who undergo CABG retain the indication for 12 months of DAPT, because the systemic prothrombotic state of ACS and the native coronary disease remain after surgery. In CURE and PLATO, the benefit of the P2Y12 inhibitor was consistent in patients who underwent CABG, although CABG was a postrandomization event and many patients did not resume study drug. In patients with ACS treated with DAPT who undergo CABG, the P2Y12 inhibitor is resumed after surgery to complete 12 months of DAPT (2016 update, Class 1, C-LD), typically 24 to 72 hours after surgery when bleeding risk is not excessive (2025 ACC/AHA, Table 8). In patients with stable coronary disease, DAPT after CABG may be reasonable to improve vein graft patency (2016 update, Class 2b, B-NR); aspirin alone is the standard.

Management of oral P2Y12 inhibitors before CABG, from the 2025 ACC/AHA ACS guideline (Table 8). For all patients, the oral P2Y12 inhibitor is resumed after surgery when bleeding risk is not excessive (typically 24 to 72 hours). Platelet transfusion does not reverse ticagrelor effectively while the drug or its active metabolite is circulating.

Bridging with cangrelor. When a recently stented patient at high thrombotic risk needs surgery that requires stopping the oral P2Y12 inhibitor, intravenous cangrelor can maintain P2Y12 inhibition until shortly before the operation. In BRIDGE (patients with ACS or a stent awaiting CABG after stopping a thienopyridine), cangrelor 0.75 μg/kg per minute kept platelet reactivity low in 98.8% of patients versus 19.0% with placebo, without a significant increase in CABG-related bleeding (11.8% versus 10.4%). The infusion is stopped 1 to 6 hours before surgery, and platelet function recovers within about 1 hour. Small-molecule glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) have been used for bridging in observational series; their kidney-dependent clearance prolongs offset in kidney disease, and the evidence is limited. Bridging is reserved for patients in whom the interval since stenting is short or the stent-thrombosis risk is otherwise very high; most patients undergo surgery after a simple interruption.

Noncardiac surgery in patients taking DAPT

The timing of elective noncardiac surgery after stenting, the risk stratification of procedural bleeding, and the perioperative management of antiplatelet drugs are covered in Perioperative cardiovascular evaluation and management for noncardiac surgery. The 2016 focused update recommends that elective noncardiac surgery be delayed 30 days after bare-metal stent implantation and optimally 6 months after drug-eluting stent implantation (Class 1, B-NR). Elective surgery after drug-eluting stent implantation, with the P2Y12 inhibitor stopped, may be considered after 3 months if the risk of further delay is greater than the expected risks of ischemia and stent thrombosis (Class 2b, C-EO). Elective surgery requiring P2Y12 inhibitor discontinuation should not be performed within 30 days of bare-metal stent implantation or within 3 months of drug-eluting stent implantation (Class 3: Harm, B-NR). Aspirin is continued when possible, and the P2Y12 inhibitor is restarted as soon as possible after surgery (Class 1). The 2024 AHA/ACC perioperative guideline lengthens the interval after drug-eluting stent implantation. Elective noncardiac surgery is delayed for at least 12 months after ACS, and a delay of at least 6 months is reasonable after PCI for chronic coronary disease. Time-sensitive surgery may be considered no sooner than 3 months after PCI, and elective surgery that requires interruption of 1 or more antiplatelet agents within 30 days of stent implantation is harmful. Nondeferrable major surgery on DAPT is an ARC-HBR major criterion, so a patient known to need such surgery is planned for the shortest DAPT course that the stent and presentation allow.

Patients who also require oral anticoagulation

Atrial fibrillation, venous thromboembolism, mechanical valves, and left ventricular thrombus create an indication for anticoagulation in a substantial minority of patients after PCI. In patients with ACS who require oral anticoagulant therapy, aspirin is discontinued after 1 to 4 weeks of triple antithrombotic therapy, with continued use of a P2Y12 inhibitor (preferably clopidogrel) and an oral anticoagulant (2025 ACC/AHA, Class 1, B-R); a direct oral anticoagulant is preferred over a vitamin K antagonist in most patients. Aspirin may be continued for up to 30 days after PCI in patients at high risk of stent thrombosis. The P2Y12 inhibitor, usually clopidogrel, is continued with the anticoagulant through 12 months after ACS and through 6 months after elective PCI (2023 AHA/ACC chronic coronary disease guideline, Class 1, B-R). The anticoagulant is then continued alone in most patients (2023 ACC/AHA/ACCP/HRS atrial fibrillation guideline, Class 1, B-R). Prasugrel and ticagrelor are not routinely used in combination with an anticoagulant. The trials (WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI), the decision beyond 12 months, and drug-specific dosing are covered in Antithrombotic therapy in atrial fibrillation with PCI and Atrial fibrillation. The DAPT and PRECISE-DAPT scores were derived in patients without anticoagulation and are not used in this setting.

Gastrointestinal protection with proton pump inhibitors

The upper gastrointestinal tract is the most common site of spontaneous bleeding on DAPT. Aspirin causes mucosal injury and impairs platelet-dependent hemostasis of existing lesions; P2Y12 inhibitors impair healing of ulcers and erosions. Risk factors for gastrointestinal bleeding on antithrombotic therapy include prior gastrointestinal bleeding or ulcer, age 65 years or older, concomitant anticoagulant, corticosteroid, or NSAID use, and Helicobacter pylori infection.

In COGENT (3,873 patients on aspirin and clopidogrel), omeprazole reduced gastrointestinal events from 2.9% to 1.1% at 180 days (hazard ratio 0.34) and overt upper gastrointestinal bleeding (hazard ratio 0.13), with no difference in cardiovascular events (4.9% versus 5.7%; hazard ratio 0.99). The trial ended early for loss of funding, so its cardiovascular confidence interval is wide. Omeprazole and esomeprazole inhibit CYP2C19 and attenuate the pharmacodynamic effect of clopidogrel ex vivo; post hoc analyses of randomized trials have not shown an increase in ischemic events with clinically indicated proton pump inhibitors, and the effects of ticagrelor and prasugrel are not modified. Pantoprazole has the least effect on CYP2C19 in pharmacodynamic studies. Histamine-2 receptor antagonists are less effective for bleeding prevention.

US recommendations. In patients at high risk of gastrointestinal bleeding, a proton pump inhibitor is recommended in combination with DAPT, oral anticoagulants, or both to reduce the risk of bleeding (2025 ACC/AHA, Class 1, A). The 2023 AHA/ACC chronic coronary disease guideline rates a proton pump inhibitor as reasonable in patients taking DAPT (Class 2a). The 2023 ESC ACS guideline recommends a proton pump inhibitor in patients on antithrombotic therapy at high risk of gastrointestinal bleeding (Class I).

Adverse effects, adherence, and premature discontinuation

Bleeding as the cause of stopping. Nuisance bleeding (bruising, epistaxis, gum bleeding), corresponding to BARC type 1, is common on DAPT and leads to self-discontinuation. A bleeding event on DAPT prompts a change in strategy (aspirin withdrawal, de-escalation, or shortening). Stopping all antiplatelet therapy is reserved for life-threatening bleeding, with resumption once hemostasis is secured.

Ticagrelor dyspnea and bradyarrhythmia. Dyspnea occurs in about 10% to 15% of patients after ACS, is usually mild and transient, appears in the first weeks, and is related to adenosine-mediated effects. It is not associated with changes in pulmonary or cardiac function, but it leads many patients to stop ticagrelor; heart failure, anemia, and bronchospasm are excluded before the symptom is attributed to the drug. Persistent intolerable dyspnea is managed by switching to prasugrel or clopidogrel using the regimens in the switching table. Ticagrelor causes ventricular pauses, mostly asymptomatic and in the first week, and is used with caution in patients with sick sinus syndrome or high-grade atrioventricular block without a pacemaker. Ticagrelor also raises serum uric acid and creatinine modestly.

Rebound after stopping. In the DAPT Study, stent thrombosis and MI rose in both groups in the 3 months after the thienopyridine was stopped, at 12 and at 30 months. Whether the increase reflects a true rebound of platelet reactivity or loss of protection in high-risk patients is unresolved, but it argues for planned, not abrupt, transitions and for reassessment at each step.

Adherence and cost. Adherence to DAPT falls over the first year and with each additional daily dose. Clopidogrel and prasugrel are available as generics in the United States, and cost differences among the P2Y12 inhibitors influence long-term adherence. Patients receive written instructions not to stop the P2Y12 inhibitor without consulting the cardiology team, and dentists, endoscopists, and surgeons are told the stent date and the planned DAPT end date.

DAPT in diabetes, kidney disease, older age, complex PCI, and other special populations

Diabetes. Patients with diabetes have higher rates of stent thrombosis and recurrent MI and greater benefit from potent P2Y12 inhibition; in TRITON-TIMI 38 the benefit of prasugrel was greater in diabetes. Diabetes is a DAPT-score item and a PEGASUS enrollment feature. Shortening and aspirin-withdrawal strategies were consistent in diabetic subgroups of TWILIGHT and TICO.

Chronic kidney disease. Kidney disease raises both bleeding and ischemic risk, is an ARC-HBR criterion at eGFR below 60 mL/min, and is a PRECISE-DAPT variable as creatinine clearance. Patients on dialysis were underrepresented in the duration trials. No dose adjustment of clopidogrel, prasugrel, or ticagrelor is required for kidney function, but the absolute bleeding risk on DAPT is high, and in end-stage kidney disease the evidence for ticagrelor and prasugrel is limited.

Older adults. Age 75 years or older is an ARC-HBR minor criterion. In PRECISE-DAPT, age contributes up to 19 points, less than prior spontaneous bleeding (26 points) or creatinine clearance (up to 25 points); age 75 years or older subtracts 2 points from the DAPT score. Prasugrel is generally avoided at this age. In POPular AGE, clopidogrel reduced bleeding compared with ticagrelor in NSTE-ACS patients 70 years or older, with noninferior net benefit, and 47% of patients assigned to ticagrelor stopped it prematurely. Older patients were well represented in MASTER DAPT and in the high-bleeding-risk stent trials.

Women. Women have higher bleeding rates on DAPT, partly from lower body weight and kidney function and from access-site complications, and are underrepresented in the trials. Treatment effects of shortening and aspirin withdrawal were consistent by sex in the major trials.

Complex PCI and left main stenting. Complex PCI (features in the ischemic-risk table above) raises stent-related risk, and patients with recent stent thrombosis or the most complex anatomy were often excluded from monotherapy trials. In complex-PCI subgroups of TWILIGHT and pooled analyses, ticagrelor monotherapy after 3 months reduced bleeding without an ischemic penalty. Intravascular imaging guidance lowers stent-related events, and an optimized result is part of the case for shorter DAPT after complex PCI.

Drug-coated balloons. Drug-coated balloon angioplasty without a stent leaves no permanent metal, and shorter DAPT is a stated rationale for the strategy, particularly in in-stent restenosis, small vessels, and high bleeding risk. No US guideline specifies a DAPT duration after drug-coated balloon angioplasty of de novo lesions. In REC-CAGEFREE I (2,272 Chinese patients with de novo lesions), a drug-coated balloon strategy with rescue stenting did not meet noninferiority compared with intended stenting for device-oriented events at 24 months.

East Asian patients. East Asian patients have a higher prevalence of CYP2C19 loss-of-function alleles, lower thrombotic event rates for a given level of platelet inhibition, and higher bleeding rates with potent agents, a combination sometimes termed the East Asian paradox. Many short-DAPT, clopidogrel-monotherapy, and de-escalation trials were conducted in Korea and Japan, and lower prasugrel doses (3.75 mg) are approved in Japan, so extrapolation of these results to other populations is limited.

Cancer and thrombocytopenia. Active cancer within 12 months and platelets below 100 × 10⁹/L are ARC-HBR major criteria. Many oncology protocols cause thrombocytopenia, and DAPT is commonly modified (shortened, de-escalated, or interrupted) according to the platelet count and the bleeding sites of the tumor, with radial access and drug-eluting stents that permit short DAPT.

Pregnancy. Low-dose aspirin is considered safe in pregnancy; data for P2Y12 inhibitors are limited to case series, and clopidogrel has the most experience. Spontaneous coronary artery dissection (SCAD) is a common cause of ACS in pregnancy and is often managed without stenting; DAPT after SCAD without a stent is not supported by randomized evidence. These topics are covered in Acute coronary syndromes, SCAD, arrhythmias and thromboembolism in pregnancy.

DAPT outside coronary stenting: stroke, peripheral artery disease, and transcatheter aortic valve replacement

Short-term DAPT has a separate evidence base in cerebrovascular disease. In CHANCE (minor stroke or high-risk transient ischemic attack in China), clopidogrel plus aspirin started within 24 hours and continued for 21 days reduced recurrent stroke compared with aspirin alone (8.2% versus 11.7%) without more moderate or severe hemorrhage. In POINT (4,881 patients in an international trial), 90 days of clopidogrel plus aspirin reduced major ischemic events from 6.5% to 5.0% and raised major hemorrhage from 0.4% to 0.9%, with most of the benefit in the first week. Stroke guidelines therefore use a short course of DAPT, started early and continued for 21 to 90 days, after minor stroke or high-risk transient ischemic attack. Coronary DAPT and stroke DAPT overlap when a patient with recent stenting has a stroke; the coronary plan then incorporates the stroke team's bleeding assessment, and prasugrel is stopped. Neurovascular topics are covered in Cardioembolic stroke and neurocardiology.

In peripheral artery disease, DAPT with a P2Y12 inhibitor and low-dose aspirin is reasonable for at least 1 to 6 months after endovascular revascularization (2024 ACC/AHA, Class 2a, C-LD), and low-dose rivaroxaban plus aspirin is the evidence-based long-term regimen after revascularization; details are in Peripheral artery disease. After transcatheter aortic valve replacement (TAVR) in patients without an indication for anticoagulation, aspirin alone produced less bleeding than 3 months of aspirin plus clopidogrel in POPular TAVI, without more thromboembolic events, and single antiplatelet therapy is the default; details are in Transcatheter aortic valve replacement. When TAVR and PCI are combined, the coronary indication sets the duration of DAPT.

The 2023 ESC ACS guideline keeps 12 months of DAPT as the default and supports single antiplatelet therapy (preferably a P2Y12 inhibitor) after 3 to 6 months in patients who are event-free and not at high ischemic risk, and after 1 month in high bleeding risk. It also states that prasugrel should be considered in preference to ticagrelor in ACS proceeding to PCI (Class IIa), a preference not stated by the 2025 ACC/AHA guideline.

Sources of error in DAPT duration decisions

• A 12-month default applied to a patient at high bleeding risk: the trials behind the default excluded such patients, and ARC-HBR criteria are assessed at PCI, not after the first bleed.
• Shortening by stopping the P2Y12 inhibitor early after ACS and continuing aspirin: this removes the more potent drug and was associated with more MI in SMART-DATE. The strategy with Class 1 support withdraws aspirin and continues ticagrelor.
• Clopidogrel monotherapy at 1 to 2 months after ACS presented as equivalent to ticagrelor monotherapy: it failed noninferiority in STOPDAPT-2 ACS and in the patient-level meta-analysis.
• Aspirin withdrawal at or immediately after PCI: STOPDAPT-3 and NEO-MINDSET showed early stent thrombosis signals; the supporting trials withdrew aspirin at 1 to 3 months.
• Prasugrel continued as monotherapy, or prasugrel given after stroke or transient ischemic attack: monotherapy is not established after ACS, and prior cerebrovascular events are a Class 3: Harm contraindication.
• Aspirin at more than 100 mg daily with ticagrelor: higher doses attenuated the benefit of ticagrelor in PLATO.
• The DAPT score applied at the time of PCI, or PRECISE-DAPT applied at 12 months: each score was derived for one decision point.
• CKD-EPI eGFR entered as creatinine clearance in PRECISE-DAPT, or procedural bleeding counted as prior spontaneous bleeding: both misclassify bleeding risk.
• Either score applied to a patient taking an oral anticoagulant: both were derived without anticoagulation, and the anticoagulant evidence governs.
• A single minor ARC-HBR criterion recorded as high bleeding risk: the definition requires 1 major or 2 minor criteria.
• DAPT stopped abruptly for an elective procedure within 3 months of a drug-eluting stent, or stopped without informing the cardiology team: the risk of disruption is highest in the first week.
• A proton pump inhibitor withheld from a patient at high gastrointestinal bleeding risk because of the clopidogrel interaction: the bleeding benefit is established, and pantoprazole minimizes the pharmacodynamic interaction.
• Extended DAPT combined with dual-pathway rivaroxaban, or extended DAPT continued in a patient who has bled: the extension trials enrolled only patients who tolerated DAPT without bleeding.

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