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Which long-term antiplatelet regimen for patients with acute coronary syndromes?
Andrea Picchi1, Marco Ferlini2, Ugo Limbruno1
1Interventional Cardiology Unit, Grosseto, Italy.
Insights
Prolonging dual antiplatelet therapy (DAPT) beyond 12 months after acute coronary syndromes may offer benefits but requires careful consideration of bleeding risks. Further analysis is needed to determine optimal antithrombotic strategies for long-term patient outcomes.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Dual antiplatelet therapy (DAPT) is standard for acute coronary syndromes (ACS) up to 12 months.
- Patients with ACS face persistent cardiovascular event risk, even long-term.
- Existing trials on prolonged DAPT have complex results and lack clear clinical guidance.
Purpose of the Study:
- To critically evaluate three major randomized trials (PEGASUS, DAPT-MI, TRA2P-TIMI 50) on extended DAPT.
- To assess the clinical utility of prolonging DAPT beyond 12 months for ACS patients.
- To identify the optimal antithrombotic regimen balancing thrombotic and bleeding risks.
Main Methods:
- Review and comparative analysis of three large-volume randomized clinical trials.
- Examination of study populations, antiplatelet regimens, and composite endpoints.
- Discussion of the merits of using total mortality versus cardiovascular death as a primary endpoint.
Main Results:
- Significant heterogeneity exists across trials regarding patient profiles and interventions.
- Interpretation of complex composite endpoints complicates definitive conclusions.
- The optimal antithrombotic strategy for prolonged DAPT remains unclear, with trade-offs between efficacy and safety.
Conclusions:
- Prolonging DAPT beyond 12 months for ACS requires careful risk-benefit assessment.
- Total mortality may be a more informative endpoint for long-term outcomes, including bleeding consequences.
- Further research is needed to guide personalized DAPT duration and regimen selection in ACS.
Abstract:
Dual antiplatelet therapy (DAPT ) is recommended up to 12 months in patients with acute coronary syndromes, but the risk of cardiovascular events in this group of subjects remains high, also in the long-term follow-up. The potential benefit of a prolonged period of DAPT has recently been assessed in three large-volume randomized clinical trials (PEGASUS, DAPT-MI, TRA2P-TIMI 50) but final results are quite difficult to interpret and clear indications for the clinical practice are so far lacking. A direct comparison of the three studies is challenging since relevant differences exist as to clinical features and risk profile of the study populations. Different anti-platelet drugs have been tested in addition to aspirin making it difficult to understand which antithrombotic regimen guarantees the best balance between thrombotic and haemorragic events. Finally, specific designs of these trials, evaluating complex composite end-points, may generate further difficulties in the interpretation of data. We believe that the use of total mortality rather than cardiovascular death as end-point, would better describe the long-term outcome incorporating the catastrophic consequences of bleeding. This review seeks to highlight strengths and weaknesses of these three large-volume trials and tries to establish whether or not prolonging DAPT beyond 12 months in patients with acute coronary syndromes is useful and which anti-thrombotic regimen would offer the best balance between thrombotic and bleeding risk.
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