TRIPLE VERSUS DUAL ANTITHROMBOTIC THERAPY FOR PATIENTS WHO REQUIRE ORAL ANTICOAGULATION AND UNDERGO PERCUTANEOUS CORONARY INTERVENTION: AN UPDATED META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Patients who require chronic oral anticoagulation (OAC) due to conditions such as atrial fibrillation (AF) require additional antiplatelet therapy when they undergo percutaneous coronary intervention (PCI). Current treatment options include triple antithrombotic therapy (dual antiplatelet agent [DAPT] + OAC) or dual antithrombotic therapy (single antiplatelet agent [SAPT] + OAC). There is a need to identify an optimal antithrombotic regimen in this patient population since the choice of therapy can impact both bleeding and ischemic events. We performed an updated meta-analysis of randomized controlled trials (RCTs) comparing triple antithrombotic therapy (OAC+DAPT) vs. dual antithrombotic therapy (OAC + SAPT) after PCI, including the recently completed and largest trial to date (AUGUSTUS). Searching MEDLINE and Pubmed, we performed a meta-analysis of RCTs which enrolled patients undergoing elective or urgent (due to acute coronary syndrome) PCI who were randomized to receive triple or dual antithrombotic therapy. The triple antithrombotic therapy group was treated using a strategy of OAC with either warfarin or non-vitamin K oral anticoagulant (NOAC), and DAPT (acetylsalicylic acid + P2Y12 inhibitor). The dual antithrombotic therapy group was treated with OAC, either warfarin or NOAC, in combination with SAPT consisting of either acetylsalicylic acid or a P2Y12 inhibitor. Using random effects models, we determined pooled risk ratios (RR) of clinically significant bleeding, stent thrombosis, myocardial infarction (MI), and stroke with 95% confidence intervals (CI) comparing patients randomized to triple vs. dual antithrombotic therapy. Four RCTs examining 10,026 total patients were pooled. There was a 40% reduction in clinically relevant bleeding (RR 0.60 [95% CI; 0.49-0.73]) observed among patients treated with dual vs. triple antithrombotic therapy. Patients treated with dual antithrombotic therapy demonstrated a 17% increased risk of MI (RR 1.17 [95% CI; 0.94-1.46]) and a 20% increased risk of stent thrombosis (RR 1.20 [95% CI; 0.66-2.16]) which were statistically non-significant. The risk of stroke was similar between the two therapy arms (RR 0.93 [95% CI; 0.63-1.36]) (Figure). Among patients undergoing PCI treated chronically with OACs, dual antithrombotic therapy (OAC+SAPT) significantly reduced bleeding and had similar stroke risk compared to triple antithrombotic therapy (OAC+DAPT). While patients treated with dual antithrombotic therapy had a numeric increase in their risk of MI and stent thrombosis, this did not reach statistical significance. Thus, the lower bleeding risk observed with dual antithrombotic therapy may be associated with a trade-off for a higher risk of myocardial ischemic events.