Abstract

The study aimed to assess the risk of myocardial infarction (MI) and major adverse cardiac events during non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin therapy in patients with atrial fibrillation (AF), both treated and not treated with percutaneous coronary interventions (PCI). In a systematic search, we selected eight randomized clinical trials with a total of 81,943 patients. Dabigatran, compared to warfarin, significantly increased the risk of MI (relative risk [RR] 1.38, 95% CI 1.14–1.67), while the FXa inhibitors’ effect did not differ significantly from warfarin (RR 0.96, 95% CI 0.86–1.09). The RR comparison between analyzed subgroups (dabigatran vs. FXa inhibitors) showed a significant difference (Chi2 = 9.51, df = 1, p = 0.002). In a network meta-analysis, dabigatran 110 mg b.i.d. increased the risk of MI compared to warfarin, apixaban, edoxaban, and rivaroxaban. Also, dabigatran 150 mg b.i.d. increased the risk of MI compared to warfarin, apixaban, and rivaroxaban. Moreover, we tried to estimate the treatment ranking of the best therapy for MI prevention in patients with AF treated with PCI. Rivaroxaban had a 90% probability of being ranked the best therapy for MI prevention, whereas dabigatran 110 mg had an 8.2% probability. Dabigatran 150 mg was the most effective in stroke prevention (94% probability). Each NOAC is associated with a different risk of MI. Furthermore, we should consider FXa inhibitors as the first line NOACs in AF and coronary artery disease patients. PROSPERO ID CRD42020179808.

Highlights

  • A total of 677 studies were examined for eligibility, of which nine papers were selected for eight studies, with a total of 81,943 patients who met the inclusion criteria (Figure 1). 1653 (2.1%) patients had myocardial infarction (MI)

  • Dabigatran compared to warfarin significantly increased the risk of MI (RR 1.38, 95% confidence interval (CI) 1.14–1.67)

  • Dabigatran at the dose of 110 mg b.i.d. as well as at the dose of 150 mg b.i.d. increased the risk of MI compared to warfarin, apixaban, and rivaroxaban (Figure 5)

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Summary

Introduction

The standard triple antithrombotic therapy (TAT) containing vitamin K antagonist (VKA), P2Y12 inhibitor (mainly clopidogrel), and aspirin was recommended in patients with atrial fibrillation (AF) treated with percutaneous coronary interventions (PCI). Two randomized controlled trials (RCTs) showed a significant reduction of hemorrhagic complications in patients treated with dual antithrombotic therapy (DAT). Several RCTs compared DAT containing NOAC and P2Y12 inhibitor with standard TAT [3,4,5,6]. Two most recent meta-analyses (constructed on the same RCTs) have shown that on DAT, a significant reduction in the risk of hemorrhagic complications (about 40–50%) is accompanied by an increase in the risk of myocardial infarction (MI) and stent thrombosis (ST) [12,13]

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