Ticagrelor vs Clopidogrel in ACS Patients Receiving DOAC After PCI: More Bleeding Without Ischemic Benefit?

In patients with acute coronary syndrome (ACS) who require direct oral anticoagulation (DOAC) and undergo percutaneous coronary intervention (PCI), current guidelines recommend a dual antithrombotic strategy based on a DOAC plus a P2Y12 inhibitor, avoiding the routine use of aspirin. However, direct comparative evidence between ticagrelor and clopidogrel within this therapeutic approach remains limited. The aim of this study was to compare the clinical outcomes of both drugs at one year of follow-up.

This was a cohort study based on the Swedish national SWEDEHEART registry conducted between 2014 and 2022. A total of 3,708 patients with ACS undergoing PCI and treated with a DOAC were included. Patients were divided into two groups: ticagrelor, including 1,170 patients (32%), and clopidogrel, including 2,538 patients (68%).

The primary endpoint was major adverse cardiovascular events (MACE), defined as mortality, myocardial infarction (MI), and stroke. Additional endpoints included all-cause mortality, clinically relevant bleeding, and myocardial infarction.

The mean age of the population was approximately 76 years, and most patients were men. The most common clinical presentation was non-ST-segment elevation myocardial infarction (NSTEMI) in 48% of cases, followed by ST-segment elevation myocardial infarction (STEMI) in 40% and unstable angina in 12%.

At one year of follow-up, no significant differences were observed in the incidence of MACE between the two groups: the event rate was 16.7% with ticagrelor and 16.6% with clopidogrel (HR 1.02; 95% CI: 0.84-1.23). Likewise, ticagrelor did not demonstrate superiority in terms of all-cause mortality (HR 1.24) or myocardial infarction incidence (HR 0.90).

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Conversely, ticagrelor use was associated with a significantly higher risk of clinically relevant bleeding compared with clopidogrel (4.9% vs. 3.7%; HR 1.53; 95% CI: 1.06-2.22). In subgroup analysis, a significant interaction was identified among STEMI patients, in whom ticagrelor showed a non-significant trend toward lower MACE rates, whereas the opposite trend was observed in non-STEMI patients.

The adjusted 53% increase in bleeding risk associated with ticagrelor represents a clinically relevant finding that should be carefully considered when selecting an antithrombotic strategy. These results support current 2024-2025 European and North American guideline recommendations, which position clopidogrel as the preferred P2Y12 inhibitor when dual therapy with a DOAC is required.

Conclusion: Clopidogrel Remains the Best Balance Between Efficacy and Safety in ACS Patients Requiring DOAC Therapy

In ACS patients receiving DOAC therapy and undergoing PCI, ticagrelor increases bleeding risk without reducing ischemic events or mortality compared with clopidogrel. In this setting, clopidogrel appears to remain the most balanced strategy in terms of efficacy and safety for this complex patient population.

Original Title: Ticagrelor versus clopidogrel in orally anticoagulated patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Reference: Oskar Love Emilssonn et al EuroIntervention 2026;22:575-584.