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Objectives This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention. Background Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear. Methods In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (n = 709); 2) rivaroxaban 2.5 mg twice a day plus dual antiplatelet therapy (DAPT) (n = 709); and 3) dose-adjusted warfarin plus DAPT (n = 706). Kaplan-Meier rates of clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by subgroups of procedure type and lesion characteristics. Results Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups). Conclusions Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543)

Dual antiplatelet therapy (DAPT) has been the cornerstone of antithrombotic management for patients undergoing percutaneous coronary intervention (PCI). However, approximately 10% of these patients have concomitant atrial fibrillation (AF) and require chronic oral anticoagulant (OAC) in addition to DAPT. This traditional "triple therapy" has been associated with a three to four-fold increased risk of bleeding. The safety of non-vitamin K OAC (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 PCI. This article reviews the rationale, evidence, and recent evaluation of triple antithrombotic therapy among AF patients undergoing PCI.

The concurrence of atrial fibrillation and acute coronary syndrome poses a conundrum in the antithrombotic management as intensification of anticoagulation or antiplatelet therapy inevitably comes at the price of an increased bleeding risk. Various antithrombotic combinations have been attempted to prevent the recurrent cardiovascular events, however, there has been limited success in effective risk reduction for this high risk population. Given the overarching effect of interleukin 1β-driven inflammation on the arrhythmogenesis, thrombogenesis, and hypercoagulability, we hypothesize that the triple-pathway strategy (i.e., incorporating antiinflammatory therapy into anticoagulant and antiplatelet therapy) would grant incremental cardiovascular benefits for atrial fibrillation patients with coexisting acute coronary syndrome and stent placement.

Andexanet alfa is a recombinant factor Xa decoy molecule that inhibits direct and indirect factor Xa inhibitors to allow the normal coagulation process to resume. Its development arises in a space where novel oral anticoagulants are receiving expanded indications yet their use is limited by the lack of an effective reversal agent. Areas covered: This article reviews the biochemical properties, mechanism of action and the preclinical and clinical trials on andexanet alfa. It additionally aims to provide expert commentary and future perspectives on the efficacy, safety and challenges facing andexanet alfa as a universal antidote for direct and indirect factor Xa inhibitors. Expert commentary: Andexanet alfa shows promise to become a highly effective, novel antidote for factor Xa anticoagulation. Its biochemical profile and mechanism of action are immediately more attractive than other drugs on the market and under development due to its inert nature within the normal coagulation cascade, with minimal intrinsic procoagulant or anticoagulant properties. The anticoagulant antidote space will continue to develop as more specific and universal options become available for reversal of the effect of DOACs. Preliminary results of a pivotal phase 3b/4 trial demonstrate a favorable efficacy and safety profile in patients with acute hemorrhage.