Assessment of the risk of bleeding in patients with atrial fibrillation and acute coronary syndrome treated by a direct oral anticoagulant and anti-platelets therapy
: A systematic review and meta-analysis of randomized controlled trials

  • Gautam Vasudev

Student thesis: Master typesMaster in Biomedicine Professional focus


Background: Atrial fibrillation (AF) is a common cardiac arrhythmia which confers a considerable risk of mortality and morbidity from thromboembolism and stroke. Patients exhibiting AF and coronary artery disease (CAD) with an acute coronary syndrome (ACS) or those who are undergoing percutaneous coronary intervention (PCI) present an interesting challenge, especially since such patients are likely to develop cardiovascular-related mortality and morbidity. To prevent atherothrombotic events, oral anticoagulant therapy is provided with antiplatelet therapy as an auxiliary treatment in such patients. Recent studies have demonstrated that patients on triple therapy with a Vitamin K antagonist (VKA) regimen are at an increased risk of bleeding when compared to those on direct oral anticoagulant (DOAC) triple therapy.
Aim: We aim at performing a systematic review of the literature and a meta-analysis of s randomized controlled trials in patients treated with DOACs in addition to antiplatelet therapy to assess the benefit-risk profile of this strategy. The final objective is to provide a rationale for the restriction of this strategy only in those with a high risk of thrombosis.
Methods: A literature search of journal articles was conducted in 4 electronic databases. After the relevant study selections and extraction of the data, a random effects model was used and the summary statistics collected from each trial, structured around the type of treatment and the type of outcomes was calculated using the Mantel Haenszel Odds ratio (M-H OR). A one way sensitivity analysis assessed the robustness of the findings. Funnel plots were constructed to determine publication bias.
Analysis: In the setting of AF and ACS/PCI, 4 studies were selected and in the setting of DOAC plus antiplatelet therapy vs DOAC alone in AF patients, 4 post hoc studies were selected for the statistical analysis. Observational studies were part of the discussion.
Conclusion: Our meta-analysis shows that in the setting of AF patients with ACS/PCI, dual therapy of a DOAC plus an antiplatelet (P2Y12 inhibitor like clopidogrel) is preferable over a triple therapy containing aspirin. In the setting of AF with an indication for concomitant aspirin, it was shown that there was a statistically significant increase in both major bleeding and thromboembolic events. Due to the differences in the population of the recruited patients in terms of their comorbidities, the concomitant medications and the treatment regimens administered to them and the design of the clinical trials, it is advisable for a more calculated and personalised approach in treating higher risk AF patients with the added implementation of platelet function testing (PFT) as well.
Date of Award23 Jan 2020
Original languageEnglish
Awarding Institution
  • University of Namur
SupervisorJonathan Douxfils (Supervisor)


  • Atrial fibrillation
  • acute coronary syndrome
  • percutaneous coronary
  • intervention
  • direct oral anticoagulants
  • antiplatelets

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