134 CHAPTER 8 ABSTRACT Introduction: Postmarketing observational studies report that a substantial percentage of patients with atrial fibrillation (AF) receive a reduced non-vitamin K antagonist oral anticoagulant (NOAC) dose without a clear indication. Recently, increasing evidence has become available to explore the clinical consequences of such off-label reduced dosing (OLRD). This study aims to systematically review and metaanalyse observational studies that report clinical outcomes associated with OLRD of NOACs compared with on-label non-reduced dosing (OLNRD) of NOACs in patients with AF. Methods: We performed a systematic literature review and meta-analysis of observational studies reporting clinical outcomes in AF patients with OLRD of a NOAC compared with AF patients with OLNRD of a NOAC. Using random effects metaanalyses, we estimated the risk of stroke/thromboembolism, bleeding and all-cause mortality. Results: We included 19 studies with a total of 170,394 NOAC users. In these studies, the percentage of OLRD of NOACs among patients with an indication for OLNRD ranged between 9% and 53%. 7 of these 19 studies met the predefined criteria for meta-analysis (n=80,725 patients). The pooled hazard ratio associated with OLRD of NOACs was 1.04 (95% confidence interval (CI) 0.83-1.29; 95% prediction interval (PI) 0.60-1.79) for stroke/ thromboembolism, 1.10 (95% CI 0.95-1.29; 95% PI 0.81-1.50) for bleeding, and 1.22 (95% CI 0.81-1.84; 95% PI 0.55-2.70) for all-cause mortality. Conclusion: This meta-analysis shows no statistically significant increased risk of stroke/thromboembolism, nor a decreased bleeding risk, nor a difference in risk of all-cause mortality in patients with OLRD of NOACs. Future research may focus on differences between NOACs.
RkJQdWJsaXNoZXIy MTk4NDMw