Risk of adverse effects of the concomitant use of statins with calcium channel blockers: a systematic review and meta-analysis

Calcium channel blockers (CCBs) and statins are commonly combined to prevent cardiovascular diseases (CVDs). However, their concomitant use may lead to drug-drug interactions (DDIs) and increased adverse effects (AEs). This systematic review and meta-analysis aimed to evaluate the evidence of adverse effects (AEs) associated with the calcium channel blockers (CCBs) and statins concomitant use. We searched MEDLINE, Embase, Web of Science, and CENTRAL from database inception to 4 April 2025. Eligible studies included randomized controlled trials (RCTs) and observational studies reporting AEs of CCB-statin combinations compared with CCB or statin treatment in adults. Outcomes assessed included CCBs- and statins-associated AEs, treatment discontinuation, hospitalization, and all-cause mortality. Meta-analyses of similar outcomes were performed to estimate pooled Odds Ratios (OR) with 95% confidence intervals (CI). Of 9,737 articles screened, 20 studies (n = 1,053,198) were included. Peripheral edema, myalgia, and discontinuation were most reported in 11, 7, and 9 studies, respectively. Meta-analyses demonstrated no significant differences in the risk of peripheral edema (OR 1.03, 95% CI 0.14–1.48), myalgia (OR 1.33, 95% CI 0.63–2.79), or discontinuation (OR 0.78, 95% CI 0.50–1.23 for CCB-statin vs. CCB; OR 0.97, 95% CI 0.68–1.38 for CCB-statin vs. statin). However, evidence of other AEs was inconsistent and limited. CCB-statin combination appears generally safe in a short-term use (3 to 6 months). Further research is warranted to clarify the long-term risk of AEs.