Risk of Stroke vs. Intracerebral Hemorrhage in Patients with Non-Valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing Dual vs. Triple Antithrombotic Therapy

Abstract

Background: About 15% of patients with non-valvular atrial fibrillation might require percutaneous coronary interventions (PCIs) with stent placement to treat obstructive coronary artery disease. Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (aspirin) and P2Y12 antagonist is recommended after PCI. Patients requiring DAPT also require treatment with oral anticoagulation for atrial fibrillation. We conducted a meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in non-valvular atrial fibrillation after PCI.

Methods: We searched PubMed, Embase, Scopus and Cochrane databases to identify randomized trials that investigated the use of dual antiplatelet therapy and vitamin K antagonist and/or Non-vitamin K antagonist oral anticoagulants (NOAC) (triple antithrombotic therapy (TAT)) against single antiplatelet agent and NOAC (dual antithrombotic therapy (DAT)) in the setting of coronary artery disease (CAD) requiring PCI and non-valvular atrial fibrillation. Random-effect models were used to pool data. We used the I² statistic to measure heterogeneity between trials.

Results: We found 4 randomized clinical trials (ENTRUST, AUGUSTUS, PIONEER, REDUAL) using different NOACs. Overall, 9241 patients (median age 70 years, 41.4% female, mean CHADS2VASC Score 3.5) were included. We excluded patients in the very low dose rivaroxaban group from the PIONEER AF-PCI trial and low dose dabigatran group from the REDUAL PCI trial as these are not available in the United States. Our metanalysis showed that dual therapy was associated with less risk of intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.99; p = 0.045; I² = 42%) and major bleeding (RR 0.66; 95% CI 0.55-0.79; p < 0.0001; I² = 27%) as compared to triple therapy. Further risk of ischemic stroke (RR 0.94, 95% CI 0.63-1.39; p = 0.75; I²=0%), myocardial infarction (RR 1.18, 95% CI 0.94-1.47; p = 0.16; I² = 0), or stent thrombosis (RR 0.50, 95% CI 0.93-2.41; p = 0.10; I² = 0%) were unchanged. Similar findings were also noted on analysis of NOAC specific DAT vs VKA based TAT.

Conclusions: The combination of an antiplatelet and NOACs (dual therapy) is associated with less risk of major bleeding and intracranial hemorrhage, with no significant difference in ischemic events (stroke myocardial infarction or stent thrombosis).

Keywords: Anticoagulation; Atrial fibrillation; Coronary artery disease; Non vitamin K oral anticoagulants; Percutaneous coronary intervention.