Effectiveness and Safety of Apixaban in over 3.9 Million People with Atrial Fibrillation: A Systematic Review and Meta-Analysis

Abstract

Background: There is a plethora of real-world data on the safety and effectiveness of direct-acting oral anticoagulants (DOACs); however, study heterogeneity has contributed to inconsistent findings. We compared the effectiveness and safety of apixaban with those of other direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKA e.g., warfarin). Methods: A systematic review and meta-analysis was conducted retrieving data from PubMed, SCOPUS and Web of Science from January 2009 to December 2021. Studies that evaluated apixaban (intervention) prescribed for adults (aged 18 years or older) with AF for stroke prevention compared to other DOACs or VKAs were identified. Primary outcomes included stroke/systemic embolism (SE), all-cause mortality, and major bleeding. Secondary outcomes were intracranial haemorrhage (ICH) and ischaemic stroke. Randomised controlled trials and non-randomised trials were considered for inclusion. Results: In total, 67 studies were included, and 38 studies were meta-analysed. Participants taking apixaban had significantly lower stroke/SE compared to patients taking VKAs (relative risk (RR) 0.77, 95% confidence interval (CI) 0.64–0.93, I2 = 94%) and dabigatran (RR 0.84, 95% CI 0.74–0.95, I2 = 66%), but not to patients administered rivaroxaban. There was no statistical difference in mortality between apixaban and VKAs or apixaban and dabigatran. Compared to patients administered rivaroxaban, participants taking apixaban had lower mortality rates (RR 0.83, 95% CI 0.71–0.96, I2 = 96%). Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52–0.65, I2 = 90%), dabigatran (RR 0.79, 95% CI 0.70–0.88, I2 = 78%) and rivaroxaban (RR 0.61, 95% CI 0.53–0.70, I2 = 87%). Conclusions: Apixaban was associated with a better overall safety and effectiveness profile compared to VKAs and other DOACs.

Anticoagulant drugs for patients with atrial fibrillation on dialysis: a systematic analysis and network meta-analysis

“…Neither network nor traditional meta-analysis indicated that DOACs were ineffective in reducing intracranial hemorrhage. Consistent with the present study (Buckley et al, 2022), the use of DOACs did not yield beneficial outcomes in terms of reducing bleeding rates among ESRD patients with AF undergoing dialysis. Among patients receiving dialysis and diagnosed with AF, treatment with DOACs was associated with a 28% increased risk of bleeding events.…”

Back to the Future: Observational Studies and Anticoagulant Selection for Nonvalvular Atrial Fibrillation

“…Results concur with several studies showing lower gastrointestinal and nonintracranial bleeding rates for apixaban compared with other DOACs. 2,10,11 Findings were consistent across a suite of thoughtfully selected sensitivity and subgroup analyses and were robust when using an intention-to-treat rather than an on-treatment exposure definition. Characterizing major bleeding as hospitalization for any bleeding is a sensitive definition that reduces misclassification Stroke.…”

Use of apixaban in children awaiting heart transplantation

“…While our center can receive same day results for apixaban levels, we do realize that is not an option at all institutions. The described prophylactic and therapeutic apixaban levels have been demonstrated to have appropriate efficacy, safety, and low events rates in an analysis 219 pediatric patients, along with five HM3 VAD patients, from our institution, 17,18 along with a large meta‐analysis in adults 19 . It has been demonstrated that chromogenic anti‐factor Xa assay calibrated with heparin standards shows a correlation between apixaban levels and LMWH levels 20 .…”

“…The described prophylactic and therapeutic apixaban levels have been demonstrated to have appropriate efficacy, safety, and low events rates in an analysis 219 pediatric patients, along with five HM3 VAD patients, from our institution, 17,18 along with a large meta-analysis in adults. 19 It has been demonstrated that chromogenic anti-factor Xa assay calibrated with heparin standards shows a correlation between apixaban levels and LMWH levels. 20 These previously described findings correlate with our experience as well, with a goal LMWH of greater than 1.5 units/mL suggesting appropriate apixaban anticoagulation.…”