Systematic review and network meta-analysis of stroke prevention treatments in patients with atrial fibrillation

Abstract

Background: In the last 4 years, four novel oral anticoagulants have been developed as alternatives to warfarin and antiplatelet agents for stroke prevention in atrial fibrillation (AF) patients. The objective of this review was to estimate the comparative effectiveness of all antithrombotic treatments for AF patients.

Materials and methods: Data sources were Medline Ovid (1946 to October 2015), Embase Ovid (1980 to October 2015), and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 9, 2015). Randomized controlled trials of AF patients were selected if they compared at least two of the following: placebo, aspirin, aspirin and clopidogrel combination therapy, adjusted-dose warfarin (target international normalized ratio 2.0-3.0), dabigatran, rivaroxaban, apixaban, and edoxaban. Bayesian network meta-analyses were conducted for outcomes of interest (all stroke, ischemic stroke, myocardial infarction, overall mortality, major bleeding, and intracranial hemorrhage).

Results: Based on 16 randomized controlled trials of 96,826 patients, all oral anticoagulants were more effective than antiplatelet agents at reducing the risk of ischemic stroke and all strokes. Compared to warfarin, dabigatran 150 mg (rate ratio 0.65, 95% credible interval 0.52-0.82) and apixaban (rate ratio 0.82, 95% credible interval 0.69-0.97) reduced the risk of all strokes. Dabigatran 150 mg was also more effective than warfarin at reducing ischemic stroke risk (rate ratio 0.76, 95% credible interval 0.59-0.99). Aspirin, apixaban, dabigatran 110 mg, and edoxaban were associated with less major bleeding than warfarin.

Conclusion: All oral anticoagulants reduce the risk of stroke in AF patients. Some novel oral anticoagulants are associated with a lower stroke and/or major bleeding risk than warfarin. In addition to the safety and effectiveness of drug therapy, as reported in this study, individual treatment recommendations should also consider the patient's underlying stroke and bleeding risk profile.

Keywords: atrial fibrillation/prevention and control; cerebrovascular disorders/drug therapy; meta-analysis; platelet-aggregation inhibitors; stroke prevention.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the study-selection process. Abbreviations: RCTs, randomized controlled trials; MTC, multiple-treatment comparison.

Figure 2

Network of evidence. Notes: (A) Base-case multiple-treatment comparison analysis; (B) sensitivity analysis. The nodes represent the choice of stroke prophylactic treatment and the lines connecting the nodes represent direct comparisons from randomized controlled trials. The diameter of the nodes represents the number of patients receiving the intervention; the width of the lines and the numbers next to them indicate the number of direct comparisons. Abbreviations: ASA, acetylsalicylic acid (aspirin); APX, apixaban; C, clopidogrel; DAB 110, dabigatran 110 mg; DAB 150, dabigatran 150 mg; EDX HD, high-dose edoxaban; EDX LD, low-dose EDX; RVX, rivaroxaban; WAR, warfarin.

Figure 3

Ranking distributions of each treatment for ischemic stroke (efficacy) and major bleeding (safety). Notes: Distributions based on 100,000 Markov chain Monte Carlo simulations. Ranking indicates the probability that a treatment is ranked first (best) to tenth (worst) with respect to both outcomes. Abbreviations: LD, low dose; HD, high dose.