Statin Lipophilicity and the Risk of Incident Heart Failure

To compare the risk of incident heart failure (HF) between initiators of hydrophilic and lipophilic statins.

Using claims data for commercial health insurance program enrollees in the USA (2005-2014), we identified new initiators of hydrophilic or lipophilic statins. Follow-up for the primary outcome of incident HF began after a lag period of 1 year after statin initiation. The outcome was defined as 1 inpatient or 2 outpatient diagnosis codes for HF and the use of loop diuretics. Propensity scores (PS) were used to account for confounding. Hazard ratios (HR) for incident HF were computed separately for low and high-intensity statin users, and then pooled to provide dose-adjusted effect estimates.

A total of 7,820,204 patients met all our inclusion criteria for statin initiation (hydrophilic and lipophilic statins). Mean age was 58 years, 40% had hypertension, and 23% had diabetes mellitus. After PS matching, there were 691,584 patients in the low-intensity statin group and 807,370 patients in the high-intensity statin group. After a median follow-up of 725 days (IQR 500-1,153),there were 8,389 cases of incident HF (incidence rate 4.5/1,000 person years, 95% confidence interval [CI] 4.4-4.6). The unadjusted HR for the risk of HF was 0.77 (95% CI 0.76-0.79) and the pooled adjusted HR for incident HF after PS matching was 0.94 (95% CI 0.90-0.98) for hydrophilic versus lipophilic statins. The HR for incident HF was 1.06 (95% CI 1.00-1.12) for hydrophilic versus lipophilic statins for the low-intensity statin group and 0.82 (95% CI 0.78-0.87) for the high-intensity statin group. In subgroup analyses, a similar trend persisted for those younger and older than 65 years and when comparing rosuvastatin with atorvastatin.

In this observational cohort study, hydrophilic statins were associated with a modest risk reduction in incident HF as compared to lipophilic statins. Future research replicating these findings in different populations is recommended.