Statin Therapy in Non-ischemic Cardiomyopathy: evidence from a Population Based Cohort and Mendelian Randomization Analysis

Abstract Aims Statin therapy is widely used for atherosclerotic cardiovascular disease. However, evidence of benefits in patients with non-ischemic cardiomyopathy (NICM) remains controversial. Thus, this study aimed to examine the association between statin use and mortality risk in NICM patients and investigate the causal role of statin therapy on NICM. Methods and Results We included NICM patients from a heart failure (HF) surveillance cohort abstracted from ARIC study. Kaplan-Meier estimates and logistic regression analysis were used to investigate the associated risk. In mendelian randomization (MR) analysis, summary-level GWAS data for statins SNPs were obtained through UK Biobank while data for NICM were obtained from FinnGen GWAS. Five MR methods were used to investigate the potential causality between statin therapy and NICM. 372 NICM patients were included in the population-based cohort, with 44% (164/372) reported as statin users. Overall, the 28-day and 1-year mortality rate were 5.11% (19/372) and 27.96% (104/372), respectively. In logistic regression analysis, statin use was associated with lower risk of 28-day (Odds Ratio [OR] 0.14, P=0.009) and 1-year mortality (OR 0.81, P=0.37) in the non-adjusted models. In MR analysis, estimates were concordant and similar in size in all MR methods, supporting a protective effect of statin use against NICM. The Cochran’s Q test suggested no evidence of heterogeneity in the instrumental variables while MR-Egger test showed no sign of directional pleiotropy. ConclusionThis study provides evidence of a beneficial effect of statin use on NICM. This could have significant implications for current HF management in NICM patients.