BACKGROUND: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
BACKGROUND:Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ≥3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ≥3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.
Authors: Stuart J Connolly; Michael D Ezekowitz; Salim Yusuf; Paul A Reilly; Lars Wallentin Journal: N Engl J Med Date: 2010-11-04 Impact factor: 91.245
Authors: Lesley Wood; Matthias Egger; Lise Lotte Gluud; Kenneth F Schulz; Peter Jüni; Douglas G Altman; Christian Gluud; Richard M Martin; Anthony J G Wood; Jonathan A C Sterne Journal: BMJ Date: 2008-03-03
Authors: Stuart J Connolly; Michael D Ezekowitz; Salim Yusuf; John Eikelboom; Jonas Oldgren; Amit Parekh; Janice Pogue; Paul A Reilly; Ellison Themeles; Jeanne Varrone; Susan Wang; Marco Alings; Denis Xavier; Jun Zhu; Rafael Diaz; Basil S Lewis; Harald Darius; Hans-Christoph Diener; Campbell D Joyner; Lars Wallentin Journal: N Engl J Med Date: 2009-08-30 Impact factor: 91.245
Authors: Julie C Lauffenburger; Joel F Farley; Anil K Gehi; Denise H Rhoney; M Alan Brookhart; Gang Fang Journal: Am J Cardiol Date: 2015-02-02 Impact factor: 2.778
Authors: Ghanshyam Palamaner Subash Shantha; Prashant D Bhave; Saket Girotra; Denice Hodgson-Zingman; Alexander Mazur; Michael Giudici; Elizabeth Chrischilles; Mary S Vaughan Sarrazin Journal: Circ Cardiovasc Qual Outcomes Date: 2017-04