Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF‐TIMI48 Trial

Abstract

BackgroundWe studied the concomitant use of single antiplatelet therapy (SAPT) on the efficacy and safety of the anti‐Xa agent edoxaban in patients with atrial fibrillation (AF).Methods and Results ENGAGE AF‐TIMI 48 was a randomized trial that compared 2 dose regimens of edoxaban with warfarin. We studied both the approved high‐dose edoxaban regimen (HDER; 60 mg daily reduced by one half in patients with anticipated increased drug exposure), as well as a lower‐dose edoxaban regimen (LDER; 30 mg daily, also reduced by one half in patients with anticipated increased drug regimen). SAPT (aspirin in 92.5%) was administered at the discretion of the treating physician. Cox proportional hazard regressions stratified by SAPT at 3 months with treatment as a covariate were performed. The 4912 patients who received SAPT were more frequently male, with histories of coronary artery disease and diabetes, and had higher CHADS 2Vasc and HAS BLED scores than did the 14 977 patients not receiving SAPT. When compared to patients not receiving SAPT, those receiving SAPT had a higher incidence of major bleeding; (adjusted hazard ratio [HR adj]=1.46; 95% CI, 1.27–1.67, P<0.001). SAPT did not alter the relative efficacy of edoxaban compared to warfarin in preventing stroke or systemic embolic events (SEEs): edoxaban versus warfarin without SAPT, hazard ratio (HR adj for HDER)=0.94; (95% CI: 0.77–1.15) with SAPT, HR adj=0.70 (95% CI: 0.50–0.98), P interaction (P int)=0.14. (HR adj for LDER versus warfarin without SAPT=1.19 (95% CI 0.99–1.43) With SAPT, 1.03 (95% CI, 0.76–1.39) P int=0.42. Major bleeding was lower with edoxaban than warfarin both without SAPT, HR adj for HDER=0.80 (95% CI, 0.68–0.95), and with SAPT, HR adj=0.82 (95% CI, 0.65–1.03; P int=0.91). For LDER without SAPT (HR adj=0.56 [95% CI 0.46–0.67]) and with SAPT (HR adj=0.51 [95% CI 0.39–0.66]).ConclusionsPatients with AF who were selected by their physicians to receive SAPT in addition to an anticoagulant had a similar risk of stroke/SEE and higher rates of bleeding than those not receiving SAPT. Edoxaban exhibited similar relative efficacy and reduced bleeding compared to warfarin, with or without concomitant SAPT.Clinical Trial Registration URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00781391.

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

“…The use of antiplatelet therapy in combination with oral anticoagulation in AF patients is not uncommon in both real‐world registries and randomized trials, ranging from 24% to 37%. However, in the present study we found that only a small percentage (6.1%) of NVAF patients who initiate NOAC continued with antiplatelet therapy.…”

VKORC1 and CYP2C9 polymorphisms related to adverse events in case-control cohort of anticoagulated patients

“…Santos et al [42] showed that simultaneous use of warfarin and amiodarone was not associated with adverse events in chronic OAC therapy. Also, a previous study [43] found that the combination of single antiplatelet therapy with an anticoagulant was associated with a significantly greater risk of bleeding. Sconce et al [44] showed that simvastatin reduced the mean warfarin dose in patients on chronic OAC therapy, whereas the statin effect on bleeding risk in patients on VKA is controversial.…”

How I use anticoagulation in atrial fibrillation

“…Her risk should be managed at the time of catheterization; bleeding may be reduced with a radial artery approach (versus femoral) and careful medical management (eg, dose and selection of glycoprotein IIb/IIIa and/or P2Y 12 inhibitors [ie, clopidogrel vs prasugrel or ticagrelor]); stent selection (bare metal vs drug eluting vs newer-generation drug eluting) could influence the intensity and duration of concomitant antiplatelet therapy; and her aspirin dose should be reduced (81 mg). 53 There is mounting evidence that aspirin may not be needed at all in this scenario, and it does increase the risk of bleeding 19,[54][55][56] ; however, any discussion around aspirin discontinuation should involve the cardiac interventionalist. In addition, a proton pump inhibitor may be reasonable to reduce her risk of GI bleeding.…”