Antithrombotic therapy with vitamin K antagonist (VKA) and aspirin plus a P2Y12 inhibitor has been the cornerstone of medication regimen among stented patients with atrial fibrillation (AF) for decades. However, this traditional “triple therapy” (TAT) has been associated with a three to four-fold increased risk of bleeding. The ISAR Triple and WOEST Trial demonstrated that VKA in addition to one antiplatelet therapy was associated with a reduced risk of bleeding compared to the triple therapy. More recently, safety of non-Vitamin K oral anti-coagulant (NOAC)-based strategies, using a NOAC plus a P2Y12 inhibitor, has been compared to vitamin K antagonist (VKA)-based triple therapy, in the PIONEER AF-PCI and REDUAL PCI randomized trials; both of which have demonstrated that NOAC-based strategies are safer and provide an attractive alternative to VKA-based triple therapy among AF patients who undergo percutaneous intervention (PCI). However, none of these randomized controlled trials was powered to assess the efficacy of dual anti-thrombotic (DAT) strategies. The higher safety associated with DAT has brought this fresh treatment modality into the limelight.
Given this background, Dr. Harsh Golwala, MBBS (Brigham and Women’s Hospital, Boston, MA) and his colleagues performed a systematic review and meta-analysis of 4 randomized trials comparing DAT versus VKA based TAT. Data from 5,317 subject enrolled in the WOEST, ISAR-TRIPLE, PIONEER AF-PCI, and RE-DUAL PCI trials were included in this analysis. The authors concluded that the use of dual instead of triple antithrombotic therapy (DAT vs. TAT) was associated with a 47% relative reduction in the risk of TIMI major or minor bleeding (4.3% vs 9.0%; HR 0.53 (0.36-0.85); 95% CI 0.36-0.85), with a non-significant difference for intracranial hemorrhage (HR 0.58; 95% CI 0.23-1.49). The lower risk of bleeding was not accompanied by greater risks of trial-defined MACE (10.4% vs 10.0%; HR 0.85; 95% CI 0.48-1.29) or other clinical outcomes, including all-cause mortality, cardiac death, myocardial infarction (MI), stent thrombosis, and stroke. Based on the results, the evidence points towards the fact that DAT decreases the risk of TIMI major and minor by almost half compared to TAT, while preserving the efficacy associated with the use of TAT.
Based on the results, DAT is better than TAT for bleeding outcomes and comparable to TAT for efficacy outcomes. The main issue that needs to be addressed is the most appropriate combination for DAT (aspirin, clopidogrel, prasugrel, or ticagrelor with VKAs or any specific NOAC) which would strike the right balance between minimizing thrombo-embolic vs. bleeding risks in patients. With several such combinations possible, future trials are required to answer these critical questions.