Statin Therapy and Flow-Mediated Dilation: A Systematic Review and Dose-Response Meta-Analysis Using the GRADE of Data from Randomized Controlled Trials

Abstract

Introduction: A previous meta-analysis reported the positive effects of statin therapy on endothelial function. However, the obtained result had several limitations that necessitated updating the information in this field. Therefore, a systematic and meta-analysis review was conducted to determine whether statin therapy could improve endothelial function, as assessed by flow-- mediated dilation (FMD). Methods: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science were searched to identify randomized placebo-controlled trials assessing the impact of statin therapy on FMD. A random-effects model was used for meta-analysis to calculate the mean difference in weight. Meta- regression and subgroup analyses were used to identify sources of heterogeneity. In addition, nonlinear dose-response, quality of evidence, influence analysis, and publication bias evaluation were assessed using standard methods. Result: Thirty-five trials (41 arms) involving 2178 participants were included in the meta-analysis study. Statin treatment significantly improved FMD [weighted mean difference (WMD): 1.7%, 95% CI: 1.3-2.2, p < 0.001). However, significant heterogeneity was observed (I2=97.9%, p < 0.001). The results of the subgroup analysis showed that health status can contribute to heterogeneity. Non-linear dose-response analysis revealed the most significant improvement in FMD with atorvastatin at a dose of 20 mg/day and simvastatin at 80 mg/day. Conclusion: Statin therapy significantly improved endothelial function, as assessed by FMD. These changes are clinically significant, but their use should be approached with caution.