Extended Duration Dual Antiplatelet Therapy and Mortality: A Systematic Review and Meta-Analysis

Study Questions:

In a meta-analysis of randomized, controlled trials of patients with various cardiovascular disorders, what is the effect of extended duration dual antiplatelet therapy (DAPT) on all-cause, cardiovascular, and noncardiovascular mortality?


This was a meta-analysis of randomized controlled trials that assessed the impact of extended duration versus no or short duration DAPT. Studies were eligible if participants within the study were randomly assigned to receive either extended duration DAPT (defined as aspirin and co-administration of a P2Y12 receptor inhibitor) for at least 6 months after randomization, or no or short duration DAPT, defined as aspirin alone or treatment for <6 months after randomization. Primary outcomes were all-cause, cardiovascular, and noncardiovascular mortality.


The authors identified 14 eligible studies (n = 69,644 participants) with the following study populations: 10 trials of patients with coronary artery disease after percutaneous coronary intervention or acute coronary syndrome (n = 42,616, 1,344 deaths), one trial of patients who underwent surgical revascularization for peripheral arterial disease (n = 851, 41 deaths), and one trial of patients with recent lacunar stroke (n = 3,020, 190 deaths). All trials assessed clopidogrel as the only thienopyridine apart from ARCTIC-Interruption (9% of patients received prasugrel and the remainder clopidogrel) and the DAPT study (32% received prasugrel and the remainder clopidogrel). Continued treatment, compared with aspirin alone or short duration antiplatelet therapy (≤6 months), was not associated with a difference in all-cause mortality (hazard ratio [HR], 1.05; 95% credible interval [CrI], 0.96-1.19; p = 0.33), cardiovascular mortality (HR, 1.01; 95% CrI, 0.93-1.12; p = 0.81), and noncardiovascular mortality (HR, 1.04; 95% CrI, 0.9-1.26; p = 0.66). A post hoc analysis of patients with coronary artery disease (10 studies) was consistent with results from the full analysis.


In a meta-analysis of patients with various forms of atherosclerotic cardiovascular disease, extended duration DAPT, compared to aspirin alone or shorter duration DAPT, was not associated with a difference in all-cause, cardiovascular, or noncardiovascular mortality.


The limitations of a study-based meta-analysis aside, this is an important contribution that examines the controversial issue of optimum length of dual antiplatelet therapy in patients with stable coronary artery disease. As the authors opine, their results may offer some reassurance about extended duration DAPT in a heterogeneous population of cardiovascular patients, tempering findings from the DAPT study in which patients with cardiovascular disease were randomly assigned 12 months after percutaneous coronary intervention to aspirin alone of DAPT for an additional 18 months. In DAPT, there was an increase in all-cause mortality in the DAPT group, compared with the aspirin alone group at study completion. Ultimately, the decision about duration of DAPT should be individualized, and certainly some patients may potentially benefit from an extended duration of treatment.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Vascular Medicine

Keywords: Coronary Artery Disease, Acute Coronary Syndrome, Stroke, Lacunar, Peripheral Arterial Disease, Ticlopidine, Piperazines, Aspirin, Percutaneous Coronary Intervention

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