Intracranial haemorrhages vs. stent thromboses with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous coronary intervention/acute coronary syndrome patients

AIMS : To assess the efficacy-safety profile of dual antithrombotic therapy (DAT) including direct oral anticoagulant (DOAC) vs. triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Randomized trials of AF patients with ACS/PCI, comparing DAT using DOACs against TAT, were selected. Overall, 11 161 studies were screened, 458 trials assessed, and four included, comprising 10 234 patients followed for a mean of 11 months. DAT compared to TAT resulted in significant reductions of trial-defined primary safety outcome [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.50-0.79, number needed to treat (NNT) 17] and of thrombolysis in myocardial infarction (TIMI) major bleeding (OR 0.54, 95% CI 0.41-0.70, NNT 76) and in a numerical reduction of intracranial haemorrhage (OR 0.50, 95% CI 0.21-1.19, NNT 314), which became significant after exclusion of DOACs from TAT and vitamin K antagonist from DAT arms (OR 0.31, 95% CI 0.15-0.64). There were no significant differences in the risks of cardiovascular or any deaths or stroke, but with DAT, there was a numerical increase in myocardial infarctions (MIs) (OR 1.23, 95% CI 0.99-1.54, estimated NNT for an additional harmful outcome (NNTH) 151), which became significant in the ACS/PCI subgroup (OR 1.43, 95% CI 1.02-2.00), and a 60% significant increase in stent thrombosis risk (OR 1.60, 95% CI 1.02-2.52; NNTH 274). CONCLUSION : Dual antithrombotic therapy, compared to TAT, conferred a significantly reduced risk of overall bleeding but with a significant increase of stent thrombosis risk in the overall population and a significant 43% increase of MI in the ACS/PCI subgroup.