Abstract
Background:
Several studies have reported the superiority of extended anticoagulation with rivaroxaban, apixaban, dabigatran and aspirin as superior to placebo for the prevention of recurrent venous thromboembolism (VTE). However, it is unknown if this is a class effect applicable to all direct oral anticoagulants (DOACs) or if one agent is superior. Network meta-analysis allows for indirect comparisons of agents or interventions that have not been formally evaluated in head-to-head trials while preserving randomization of the original trials.
Methods:
We performed a systematic review and network meta-analysis of randomized controlled trials that compared extended anticoagulation with DOACs to other oral agents (e.g., another DOAC, aspirin or placebo) for the prevention of recurrent VTE. We excluded data on extended treatment with vitamin K antagonists or low-molecular-weight-heparin. Data extraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Effect size estimates were calculated and pooled using techniques of network meta-analysis. Effect size was expressed as hazard ratios and 95% confidence intervals.
Results:
Six randomized trials with a total of 9,610 participants were analyzed. All trials were of high methodological quality. Prior to randomization, all participants had completed an initial period of anticoagulation for an index VTE event; the majority were treated for 6 to 18 months for an unprovoked event prior to starting extended treatment for VTE prevention. Two trials compared low-dose aspirin (100 mg daily) to placebo (ASPIRE and WARFASA), one compared rivaroxaban 10 mg or 20 mg daily to low-dose aspirin (EINSTEIN CHOICE), and the others evaluated rivaroxaban 20 mg daily (EINSTEIN-EXT), apixaban 2.5 mg or 5 mg twice-daily (AMPLIFY-EXT) and dabigatran 150 mg twice-daily (RE-SONATE) versus placebo for the prevention of recurrent VTE. The results are summarized in Figure 1b. Compared to placebo, aspirin and all DOACs effectively reduced VTE recurrence. Apixaban, rivaroxaban, and dabigatran were superior to aspirin and demonstrated comparable efficacy in preventing VTE recurrence. There was no statistically significant difference in bleeding rates between any agents compared to placebo.
Conclusion:
Our results demonstrate that all DOACs can be used interchangeably for secondary prophylaxis of VTE, likely due to a drug class effect.
No relevant conflicts of interest to declare.
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