New Oral Anticoagulants Are Not Superior to Warfarin in Secondary Prevention of Stroke or Transient Ischemic Attacks, but Lower the Risk of Intracranial Bleeding: Insights from a Meta-Analysis and Indirect Treatment Comparisons

Abstract

PurposePatients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).MethodsThree randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively.ResultsIn patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban.ConclusionNOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.

The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis

“…Although there were several previous systematic reviews investigating the efficacy and safety of TSOACs compared with conventional treatment, most of these reviews focused on a particular AF 20,[30][31][32][33][34][35][36][37] or VTE 18,19,38,39 population. To our knowledge, this is the first comprehensive analysis of bleeding outcomes from 12 phase-3 RCTs across 2 major indications for anticoagulation that incorporated .100 000 patients.…”

Practical Considerations for the Nonvitamin K Antagonist Oral Anticoagulants

“…Formal subgroup analyses indicated that the use of dabigatran, rivaroxaban, and apixaban in patients with and without previous stroke or TIA resulted in similar efficacy and safety [40,41,42]. In a meta-analysis of dabigatran, rivaroxaban, and apixaban, NOACs were as effective as warfarin in preventing stroke or SEE in patients with prior stroke/TIA with a decreased rate of intracranial bleeding; indirect comparison of any 2 of the NOACs showed similar efficacy [43]. Although no subanalysis has been performed for edoxaban, prespecified analyses showed consistent efficacy and safety regardless of patients' stroke/TIA history [7].…”

Anticoagulation and population risk of stroke and death in incident atrial fibrillation: a population-based cohort study

“…Moreover, the risks may be further attenuated by the use of direct oral anticoagulants (e.g., dabigatran, apixaban, rivaroxaban and edoxaban), which are potentially safer and easier to use than warfarin. 35 …”