Efficacy of Ranolazine for Treatment of Coronary Microvascular Dysfunction-A Systematic Review and Meta-analysis of Randomized Trials.

Kofler, Thomas; Hess, Stefanie; Moccetti, Federico; Pepine, Carl J; Attinger, Adrian; Wolfrum, Mathias; Toggweiler, Stefan; Kobza, Richard; Cuculi, Florim; Bossard, Matthias

Background Coronary microvascular dysfunction (CMD) is a common cause of angina and exercise intolerance in patients without obstructive coronary artery disease. The efficacy of ranolazine, a late sodium channel blocker, in patients with symptomatic obstructive coronary artery disease is well established. To evaluate the efficacy of ranolazine in CMD, we performed a systematic review and meta-analysis of randomized studies. Methods MEDLINE, EMBASE, Cochrane CENTRAL, and conference abstracts were searched from January 1975 to March 2020. Randomized trials evaluating ranolazine in patients with CMD were screened. Two reviewers independently extracted data and assessed study quality. End points of interest included a change in angina measured by the Seattle Angina Questionnaire (SAQ), coronary flow reserve (CFR), and clinical outcomes. Data were combined using random-effects models. Results Of 836 citations, 6 randomized studies (318 patients) were included. Median follow-up was 4 weeks. When pooling the 6 trials analyzing ranolazine, we found that patients treated with ranolazine had a higher SAQ value regarding physical functioning (mean difference, 6.42; 95% confidence interval [CI], 2.41; 10.42) quality of life (10.07; 95% CI, 3.4; 16.74), and angina stability (20.14; 95% CI, 10.12; 30.17), as well as improved CFR (0.27; 95% CI, 0.09; 0.45) compared with placebo/control therapy. A high heterogeneity was observed (range I 2, 30%-84%). Conclusions In CMD, ranolazine may be associated with improvements in CFR and some of the SAQ domains, including angina stability, physical functioning, and quality of life. However, it does not seem to beneficially impact angina frequency and treatment satisfaction. It is also unknown if it improves prognosis of afflicted patients.