Meta-analysis of clinical trials comparing triple versus dual antithrombotic therapy on risk reduction of stent thrombosis after percutaneous coronary intervention in atrial fibrillation patients

Abstract

Abstract Background Coronary artery disease (CAD) is a leading cause of mortality worldwide. Atrial fibrillation (AF) and CAD frequently coexist. Patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT) - i.e., aspirin and P2Y12 inhibitor- to prevent stent thrombosis (ST) and recurrent myocardial infarction (MI). Patients with AF and CAD are at risk of stroke. Stroke risk is reduced with oral anticoagulant therapy (warfarin) or one of the direct oral anticoagulant agents (DOACs). Patients treated with triple antithrombotic therapy (TAT)- i.e., DAPT plus oral anticoagulant therapy- suffer higher risk of major or clinically significant bleeding compared with DAT (P2Y12 and DOAC). This appeared to be statistically significant in most but not all of the randomised controlled trials (RCTs). However, it is unclear whether the risk of stent thrombosis/MI might be higher in patients treated with DAT. Previous meta-analyses have yielded conflicting conclusions. Purpose To determine the optimum antithrombotic therapy for patients with AF and CAD requiring PCI and/or ACS regarding the incidence of myocardial infarction or stent thrombosis. Methods A comprehensive literature search was done identifying all RCTs on the efficacy of antithrombotic therapy in patients with AF and ACS or PCI. A meta-analysis was performed to test the hypothesis that TAT significantly reduces the risk of stent thrombosis (ST) and MI. Results A total of 11,542 patients were included in the 5 RCTs, comparing TAT vs DAT – i.e., WOEST Trial 2013 [1], PIONEER AF-PCI 2016 [2], RE-DUAL PCI 2017 [3], ENTRUST-AF PCI 2019 [4], AUGUSTUS 2019 [5]. Triple therapy did not lead to significant reduction in risk of Myocardial Infarction (MI) [risk ratio (RR) 0.85, 95% CI 0.69–1.04, P=0.12], or Stent Thrombosis (RR 0.76, 95% CI 0.51–1.12, P=0.16). [Figure 1] On the other hand, the risk of major bleeding or clinically significant bleeding is significantly lower with DAT [Figure 2]. Conclusion DAT comprising of warfarin or DOAC and P2Y12 inhibitor reduced risk of major or clinically significant bleeding without increasing the risk of ST or recurrent MI as compared to TAT. The results encourage the use of DAT rather than TAT in patients with ACS and/or patients requiring PCI with AF who require combined antiplatelet and anticoagulant therapy. Funding Acknowledgement Type of funding sources: None. Major bleeding risk