Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis

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Background: In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT).

Methods: A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method.

Results: Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]).

Conclusions: In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

Keywords: Anticoagulation; Antiplatelet; Atrial fibrillation; Coronary artery disease; Stable ischemic heart disease.