Different diabetogenic effect of statins according to intensity and dose in patients with acute myocardial infarction: a nationwide cohort study

Abstract

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan-Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024-1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.

Keywords: Acute myocardial infarction; New-onset diabetes mellitus; Statin intensity.

Figure 1

Study schema. A total of 6152 AMI patients who were treated with moderate-to-high intensity atorvastatin and rosuvastatin were included in the final analysis. AMI acute myocardial infarction, KAMIR Korea Acute Myocardial Infarction Registry, PCI percutaneous coronary intervention; MACE major adverse cardiac events.

Figure 2

Cumulative incidence of NODM according to the statin intensity. The Kaplan–Meier curve showed the high-intensity statin group had a significantly higher cumulative incidence of NODM than the moderate-intensity statin group (7.8% vs. 5.8%; log-rank P = 0.002). NODM new-onset diabetes mellitus.

Figure 3

Cumulative incidence of NODM according to the statin intensity and dose. (A) Cumulative incidence of NODM according to the atorvastatin intensity. Patients treated with high-intensity atorvastatin showed a significantly higher cumulative incidence of NODM compared to the moderate-intensity atorvastatin group (7.2% vs. 5.8%, P = 0.002). (B) Cumulative incidence of NODM according to the atorvastatin dose. Patients treated with the 80 mg of atorvastatin had the highest cumulative incidence of NODM, followed by those on 40 mg, 20 mg and 10 mg of atorvastatin (7.7% vs. 7.1% vs. 5.8% vs. 5.7%, respectively, P = 0.484) (C) Cumulative incidence of NODM according to the rosuvastatin intensity. Patients treated with high-intensity rosuvastatin had a significantly higher cumulative incidence of NODM compared to the moderate-intensity rosuvastatin group (8.3% vs. 5.8%, P = 0.004). (D) Cumulative incidence of NODM according to the rosuvastatin Dose. Patients treated with the 20 mg of rosuvastatin showed the highest cumulative incidence of NODM, followed by 10 mg, 5 mg of rosuvastatin (8.3% vs. 5.5% vs. 2.8%, P = 0.008). NODM new-onset diabetes mellitus.

Figure 4

Cumulative incidence of MACE according to the statin intensity and dose. (A) Cumulative incidence of MACE according to the statin intensity. Patients treated with high-intensity statin showed a significantly lower cumulative incidence of MACE compared to the moderate-intensity statin group (11.6% vs. 14.1%, P = 0.004). (B) Cumulative incidence of MACE according to the atorvastatin dose. A higher dose was associated with a lower cumulative incidence of MACE (80 mg vs. 40 mg vs. 20 mg vs. 10 mg: 8.5% vs. 15.0% vs. 12.0% vs. 8.5%, respectively, P < 0.001). MACE major adverse cardiac events.