Diminished response to statins predicts the occurrence of heart failure after acute myocardial infarction

Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels using a statin is a cornerstone of preventive therapeutic management following acute myocardial infarction (AMI). In addition to its anti-atherosclerotic effects, recent studies reported a lower occurrence of heart failure (HF) under statin therapy. However, there is a wide variability in statin response. The association between the response to statin and the occurrence of HF in AMI subjects remains unclear. The purpose of present study is to examine whether the variability in statin response affects HF risk after AMI. Methods: We analyzed 505 statin-naïve AMI subjects undergoing primary percutaneous coronary intervention (PCI) who commenced atorvastatin, rosuvastatin, or pitavastatin. Statin hyporesponse was defined as a reduction in LDL-C levels <15% from baseline to 1 month after statin therapy. HF outcomes were compared between patients with and without statin hyporesponse. Results: Statin hyporesponse was identified in 15.2% (77/505) of study subjects. During a median 4.4-year observational period, statin hyporesponse was associated with a greater likelihood of HF [hazard ratio (HR) =3.01, 95% confidence interval (CI): 1.27–6.79, P=0.01]. This increased HF risk in statin hyporesponders was consistently observed in a multivariate Cox proportional hazards model (HR =2.74, 95% CI: 1.01–6.75, P=0.04), a propensity score–matched cohort (HR =12.30, 95% CI: 1.50–100.3, P=0.01) and in an inverse probability of treatment weights analysis with average treatment effects (coefficient =7.02, 95% CI: 2.29–21.58, P=0.0006). Conclusions: Hyporesponse to statins increases HF risk after AMI. Our findings highlight statin hyporesponse as a high-risk feature associated with HF events.