Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn-Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random-effects meta-analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in-hospital mortality, 30-day mortality, and thrombotic events. Low-moderate risk of bias studies were meta-analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty-eight percent of the studies (n = 5) had low-moderate risk and 72% (n = 13) had a high risk of bias. Studies with low-moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15-6.44); one study], lower in-hospital mortality [OR 0.48 (95% CI: 0.38-0.61); three studies], and reduced 30-day mortality [OR 0.49 (95% CI: 0.30-0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01-1.84); 12 studies] and reductions in 30-day mortality [OR 0.53 (95% CI: 0.37-0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low-moderate, high, or combined risk of bias groups. The evidence from low-moderate quality real-world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in-hospital and 30-day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30-day mortality risk remain significantly better with AA versus PCC.

Comparative outcomes associated with rivaroxaban versus warfarin use in elderly patients with atrial fibrillation or acute venous thromboembolism managed in the United States: a systematic review of observational studies.

BACKGROUND: Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US). METHODS: We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin. RESULTS: Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs. CONCLUSIONS: This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea.

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82-1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78-0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62-0.94) and extracranial (HR = 0.89, 95%CI = 0.81-0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA 2 DS 2 VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses. Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.