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Dual Versus Triple Therapy for AF After PCI: Review and Meta-Analysis
Study Questions:
Among patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI), how do dual therapy (P2Y12 inhibitor + direct oral anticoagulant [DOAC]) and triple therapy (dual antiplatelet therapy [DAPT] + vitamin K antagonist [VKA]) compare in terms of bleeding outcomes and ischemic events?
Methods:
A systematic literature search was conducted to identify randomized controlled trials comparing dual therapy (P2Y12 inhibitor + DOAC) and triple therapy (DAPT + VKA) in adult patients with AF undergoing PCI. Trials assessing dual therapy with P2Y12 inhibitor + VKA or dual therapy with aspirin + any anticoagulant were excluded, as were trials in which <50% of patients underwent PCI. Outcomes data extraction was based on the intention-to-treat principle. All-cause mortality and major bleeding by Thrombolysis in Myocardial Infarction (TIMI) criteria were the main endpoints of interest. Other endpoints included TIMI major and minor bleeding, trial-defined bleeding, intracerebral hemorrhage, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, stroke, and major adverse cardiovascular events (MACE). Estimates were pooled using an inverse-variance random-effects model.
Results:
From 265 manuscripts reviewed, four trials involving 7,953 patients were selected. All studies were open-label. DOAC + antiplatelet regimens studied were as follows: PIONEER AF-PCI, rivaroxaban 15 mg daily + clopidogrel or rivaroxaban 2.5 mg bid + clopidogrel and aspirin; AUGUSTUS, apixaban 5 mg BID + clopidogrel, prasugrel, or ticagrelor ± aspirin; RE-DUAL PCI, dabigatran 110 mg twice daily or 150 mg twice daily + clopidogrel or ticagrelor; and ENTRUST-AF PCI, edoxaban 30 mg daily or 60 mg daily + clopidogrel, prasugrel, or ticagrelor. All patients underwent PCI except in AUGUSTUS, in which 23.9% of patients were treated for acute coronary syndrome with medical therapy. Mean patient age was 68.6-71.9 years, and 23.6-30.7% of enrolled patients were women. Drug-eluting stents were used in 65.4-86.2% of patients. Median follow-up duration across trials was 1 year (interquartile range, 0.87-1.04 years).
High-certainty evidence demonstrated that dual therapy was associated with lower risks for TIMI major bleeding (risk difference [RD], -0.013; 95% confidence interval, -0.025 to -0.002), TIMI major and minor bleeding (RD, -0.031; CI, -0.049 to -0.012), and trial-defined bleeding (RD, -0.072; CI -0.129 to -0.015). Based on moderate-certainty evidence, there was no significant difference between dual and triple therapy in terms of intracerebral hemorrhage (RD, -0.004; CI, -0.009 to 0.000). Low-certainty evidence showed inconclusive effects of dual therapy versus triple therapy for all-cause mortality (RD, 0.004; CI, -0.010 to 0.017), cardiovascular mortality (RD, 0.001; CI, -0.011 to 0.013), MI (RD, 0.003; CI, -0.010 to 0.017), stent thrombosis (RD, 0.003; CI, -0.005 to 0.010), and MACE (RD, 0.003; CI, -0.016 to 0.023), and stroke (RD, -0.003; CI, -0.010 to 0.005). Sensitivity analyses after pooling dual therapy with dabigatran 110 mg BID showed bleeding and ischemic outcomes similar to triple therapy.
Conclusions:
Among patients with AF undergoing PCI, DOAC-based dual therapy resulted in lower risk for bleeding events compared with VKA-based triple therapy. Although there was a slight numeric increase in all-cause mortality and ischemic events with dual therapy based on low-certainty evidence, no significant differences in these endpoints were demonstrated.
Perspective:
Triple therapy has been definitively shown to increase bleeding risk, although it is difficult to know how much of the increased risk is due to VKA use and how much is related to aspirin. One limitation of this meta-analysis is that trial-level data were used, so the authors could not perform subgroup analyses based on comorbid conditions. As clopidogrel was used in >90% of patients, it was not possible to draw conclusions regarding differences among P2Y12 inhibitors. Given the signal suggesting potentially increased risk of ischemic events with dual therapy, short-term use of triple therapy following PCI in selected patients at high risk of ischemic events may be reasonable.
Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Prevention, Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS
Keywords: Acute Coronary Syndrome, Anticoagulants, Arrhythmias, Cardiac, Aspirin, Atrial Fibrillation, Drug-Eluting Stents, Hemorrhage, Intracranial Hemorrhage, Traumatic, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Secondary Prevention, Thrombosis, Vascular Diseases
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