Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials

Abstract

Aims Recently, three randomized trials reported that dual antithrombotic treatments (DATs) including non-vitamin K antagonist oral anticoagulants (NOACs) and a P2Y12 inhibitor without aspirin were associated with significantly less bleeding than vitamin K antagonist (VKA)-based triple antithrombotic therapy (TAT) in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). We conducted an analysis of pooled data from these trials. Methods and results A meta-analysis of the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials considering major bleeding [International Society on Thrombosis and Haemostasis (ISTH) and Thrombolysis in Myocardial Infarction], clinically relevant non-major bleeding, all-cause/cardiovascular death, stroke, myocardial infarction (MI), and stent thrombosis. Treatment effect is reported as odds ratio (OR) and 95% confidence interval. Among 9463 patients (53% with ACS), DAT regimens were associated with significantly less bleeding than TAT (OR 0.598, 0.491 −0.727; P < 0.001 for ISTH major bleeding), as were NOAC-based vs. VKA-based regimens (OR 0.577, 0.477 −0.698; P < 0.001). Stroke and mortality rates were similar, but there was statistically non-significant trend towards greater risk of MI (OR 1.211, 0.955 −1.535; P = 0.115) and significantly higher risk for stent thrombosis (OR 1.672, 1.022 −2.733, P = 0.041) with DAT vs. TAT (but not NOAC- vs. VKA-based regimens). This was mainly driven by Dabigatran 110 mg; the trends were lower with full-dose NOAC or Rivaroxaban 15 mg-based DATs. Conclusion Our findings support the use of full-dose NOAC (Apixaban 5 mg, Dabigatran 150 mg) or Rivaroxaban 15 mg-based treatments in most AF patients with ACS or undergoing PCI. Notwithstanding the better safety of DAT, an initial course of NOAC-based TAT may be desirable in most AF patients.

Novel Dual Therapy: A Paradigm Shift in Anticoagulation in Patients of Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

“…Lastly, another meta-analysis of latest trials of NOAC's (PIONEER-AF, RE-DUAL PCI, and AUGUSTUS trial) which included 9,463 patients also emphasized that NOAC-based regimens (DT or TT) were associated with significant reduction in bleeding events as compared with VKA-based therapeutic regimens. 31 With regard to ischemic events including stroke and death, the results were no different between DT and TT. However, there was a nonsignificant increase in rates of MI with DT, while a significant increase in stent thrombosis was observed with DT.…”

Triple therapy in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention/stenting

“…In another meta-analysis, 26 data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials were evaluated. The use of DOACs was associated with significantly lower rates of bleeding and similar rates of ischemic events (stroke, MI, and stent thrombosis) and allcause death/cardiovascular mortality than VKA-based treatments ( Table 3).…”

Three types of antithrombotic therapy in atrial fibrillation patients undergoing percutaneous coronary intervention: a meta-analysis and systematic review

“…The previous meta-analysis [8,9,10] identified that triple antithrombotic therapy (TAT) increases bleeding events relative to dual antithrombotic therapy (DAT), while NOAC decreases the risk of bleeding events as compared with VKA. However, the results of comparisons between DAT and TAT or NOAC and VKA may be more ambiguous than this.…”