ABSTRACT
Background: Low-dose prescription of rivaroxaban was common among patients with atrial fibrillation (AF) in Asia. However, the benefits and harms of rivaroxaban at a low dosage in Asian patients with AF remains unclear. Accordingly, we aimed to collect and summarize all available evidence to fill this important knowledge gap. Methods: In this systematic review and meta-analysis, we systematically searched databases of MEDLINE, EMBASE, and Cochrane Library for relevant studies from inception until February 23, 2021. Eligible retrospective nationwide or health insurance database studies or prospective registration studies that reported efficacy (stroke/systemic embolism), safety (major bleeding, intracranial hemorrhage, gastrointestinal bleeding), or other outcomes (myocardial infarction, death) of low-dose rivaroxaban in comparison with warfarin in AF patients were enrolled. Data extraction and study quality assessment were conducted by two authors independently. Low dosing of rivaroxaban (15/10 mg) was defined as the received dose lower than the recommended dose (20 mg) approved in most districts. Hazard ratio (HR) with 95% confidence intervals (95% CIs) was pooled using a random-effect model. Subgroup analyses were conducted according to different dose regimens. Sensitivity analyses were conducted by sequential elimination of each study from the pool. Since potential effect modifiers (patient demographics, differences of each study, and others) may lead to bias in primacy outcomes, we performed a meta-regression analysis to explore the influence of these factors on the primary efficacy and safety outcomes. Results: Totally, 12 studies involving 292,815 Asian patients with AF were included. All studies were detected as low to moderate risk bias. Low-dose rivaroxaban treatment in Asian AF patients was associated with a reduced risk of stroke/systemic embolism (HR: 0.76, 95% CI: 0.70-0.84, I 2 : 57.8%), major bleeding (HR: 0.72, 95% CI: 0.62-0.84, I 2 : 81.5%), and all-cause death (HR: 0.65, 95% CI: 0.58-0.73, I 2 : 81.7%) when compared with warfarin. Furthermore, consistent results were observed among different dose regimens (10/15/20 mg) in all the clinical outcomes (P interaction > 0.05 for each outcome). Meta-regression analysis failed to detect any potential confounding to impact the primacy outcomes. Conclusion: Insights from the present meta-analysis, we found that low-dose rivaroxaban, even at a dosage of 10 mg daily, was associated with a reduced risk of stroke/SE and bleeding than warfarin in Asian AF patients. However, owing to considerable heterogeneity among included studies, further prospective studies are required to confirm these findings.
ABSTRACT
BACKGROUND: There are emerging observational studies (OSs) to assess real-world comparative effectiveness and safety of direct oral anticoagulants (DOACs) in cancer associated thrombosis (CAT). We conducted a pooled and interaction analysis to compare the treatment effect estimates of DOACs between OSs and randomized controlled trials (RCTs). METHODS: We systematically searched PUBMED, EMBASE and Cochrane Library for OSs and RCTs that reported recurrent venous thromboembolism (VTE) and/or major bleeding events in CAT patients receiving DOACs and conventional anticoagulants [warfarin or low molecular-weight heparins (LMWHs)]. Relative risks (RRs) for OSs and RCTs were calculated using random-effects models separately, and interaction analyses were afterward applied to assess the comparability between OSs and RCTs. RESULTS: Baseline characteristic was comparable between identified 10 OSs (35,142 patients) and 8 RCTs (2,602 patients). Overall, no significant difference of treatment effect estimates between OSs and RCTs was detected (Pinteraction: 0.42 for recurrent VTE; Pinteraction: 0.38 for major bleeding). DOACs significantly decreased the risk of recurrent VTE compared with conventional anticoagulants in CAT patients (RR: 0.74, 95% CI: 0.63-0.86, I2: 0% for OSs; RR: 0.65, 95% CI: 0.49-0.86; I2: 0% for RCTs), without increasing major bleeding risk (RR: 0.90, 95% CI: 0.76-1.07, I2: 24.0% for OSs; RR: 1.17, 95% CI: 0.72-1.88, I2: 26.2% for RCTs). Whereas, increased risk of gastrointestinal bleeding (GIB) was found with DOACs versus conventional anticoagulants in CAT patients (RR: 2.77, 95% CI: 1.35-5.68, I2: 0% for RCTs). Analyses of subgroups, based on comparators and follow-up duration, did not significantly affect results. CONCLUSIONS: In this study, effectiveness and safety of DOACs versus conventional anticoagulants in CAT from OSs are in agreement with those from RCTs, confirming a low risk of recurrent VTE and similar risk of major bleeding in CAT patients receiving DOACs.
