Efficacy and safety of statin therapy in kidney transplant recipients: a systematic review and meta-analysis

BACKGROUND: Dyslipidemia represents an important risk factor for cardiovascular diseases, although its optimal management after kidney transplantation remains unclear. The present meta-analysis aimed to shed light on the efficacy and safety of statins among kidney transplant recipients, evaluating their potential effects on the risk of cardiovascular events, mortality and graft survival. METHODS: Medline, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from their inception through April 20, 2024. Both randomized controlled trials and observational studies evaluating the effects of statin administration after kidney transplantation were held eligible. Random-effects models were fitted using the maximum likelihood method, while the certainty of evidence was appraised following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. RESULTS: Overall, 27 studies (10 randomized controlled trials and 17 observational studies) were included. Statin use compared to no use was associated with a lower risk of major adverse cardiovascular events Relative risk (RR): 0.87, 95% confidence interval (CI): 0.67-0.96, moderate certainty and overall mortality (RR: 0.84, 95% CI: 0.74-0.94, low certainty). The risk of graft loss did not differ between the compared groups (RR: 0.72, 95% CI: 0.48-1.08, very low certainty). Regarding safety endpoints, statin use was associated with a lower risk of hepatotoxicity (RR: 0.81, 95% CI: 0.70-0.93, moderate certainty), but with a greater risk of rhabdomyolysis (RR: 1.37, 95% CI: 1.10-1.70, low certainty) and cataract (RR: 1.22, 95% CI: 1.14-1.31, moderate certainty). No statistically significant differences between the compared groups with and without statin use were observed concerning the risk of creatine kinase elevation, post-transplant diabetes mellitus, hip fracture, venous thromboembolism, or cancer. CONCLUSIONS: Among kidney transplant recipients, statin use is associated with a lower risk of cardiovascular events and better patient survival, presenting an acceptable safety profile. Further large-scale studies are needed to determine the optimal statin dosing strategy and lipid-lowering goals, depending on comorbidities and immunosuppression regimens. REGISTRATION: https://doi.org/10.17504/protocols.io.5qpvok3yzl4o/v1 .