Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation

Abstract

Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional benefit seen of anticoagulation and antiplatelet therapy for stroke prevention when compared with anticoagulation alone. There was, however, an increased risk of bleeding. Careful assessment of the indications for antiplatelet drugs in patients with atrial fibrillation who are also receiving oral anticoagulants is warranted, and future randomized comparisons are needed.

Drug–Drug Interactions with Direct Oral Anticoagulants

“…Results from DDI trials in healthy volunteers have indicated that concomitant intake of a DOAC and an antiplatelet agent (acetylsalicylic acid or clopidogrel) or a non-steroidal anti-inflammatory drug (naproxen) will increase the risk of bleeding because the bleeding time (a surrogate marker for bleeding events) substantially increased in these trials [80][81][82][83][84][85]. Data from pivotal DOAC trials and post-marketing studies verified that these combinations can relevantly increase bleeding events in anticoagulated patients, irrespective of the anticoagulant taken [86][87][88][89][90]. Subgroup analyses of and meta-analyses with data from pivotal DOAC trials in patients with non-valvular atrial fibrillation estimated that an additional intake of a single antiplatelet agent such as acetylsalicylic acid increases the risk of major bleeding 1.3-fold [86,87].…”

Antithrombotic Therapy for Atrial Fibrillation

“…Ancillary analyses show no added benefit of adding aspirin on stroke or mortality rates; however, absolute bleeding rates were higher with combination therapy, but the relative efficacy and safety with NOAC vs warfarin use were maintained irrespective of aspirin use. 294 Only the RE-LY trial showed data for combination of dabigatran with aspirin and/or clopidogrel, and as expected, major bleeding risks were increased with a single APT and further increased where 2 APTs were used. 295 Less data are evident for OAC use in AF patients with stable isolated PAD or carotid disease, in relation to OAC use.…”

Effect of concomitant antiplatelet therapy in patients with nonvalvular atrial fibrillation initiating non‐vitamin K antagonists

“…Concomitant aspirin was associated with higher rates of bleeding with no benefits in terms of ischaemic protection. In a meta‐analysis of randomized controlled trials, Kumar et al found, similarly, higher rates of haemorrhagic complications in patients with antiplatelets, with a lack of benefits for thromboembolic events (stroke/systemic embolism). Recently, the OAC‐ALONE study compared OAC alone (warfarin in 75.2% and NOAC in 24.8% of patients) to combined OAC and single antiplatelet therapy among patients with AF and stable coronary artery disease and could not establish noninferiority of OAC alone to combined OAC and APT, but the study was underpowered and inconclusive to establish the optimal antithrombotic regimen in this population because patient enrolment was prematurely terminated.…”