The role of diabetes risk factors in predicting the development of diabetes with atorvastatin therapy

Cardiovascular Event Reduction Versus New-Onset Diabetes During Atorvastatin Therapy

Effect of Baseline Risk Factors for Diabetes

J Am Coll Cardiol. 2012;():. doi:10.1016/j.jacc.2012.09.042

Abstract

Objectives:  The purpose of this study was to compare the incidence of new-onset diabetes (NOD) with cardiovascular (CV) event reduction at different levels of NOD risk.

Background:  Statins reduce the number of CV events but increase the incidence of NOD. We previously reported that 4 factors independently predicted NOD: fasting blood glucose >100 mg/dl, fasting triglycerides >150 mg/dl, body mass index >30 kg/m2, and history of hypertension.

Methods:  We compared NOD incidence with CV event reduction among 15,056 patients with coronary disease but without diabetes at baseline in the TNT (Treating to New Targets) (n = 7,595) and IDEAL (Incremental Decrease in Endpoints Through Aggressive Lipid Lowering) (n = 7,461) trials. CV events included coronary heart disease death, myocardial infarction, stroke, and resuscitated cardiac arrest.

Results:  Among 8,825 patients with 0 to 1 of the aforementioned NOD risk factors at baseline, NOD developed in 142 of 4,407 patients in the atorvastatin 80 mg group and in 148 of 4,418 in the atorvastatin 10 mg and simvastatin 20 to 40 mg groups (3.22% vs. 3.35%; hazard ratio [HR]: 0.97; 95% confidence intervals [CI]: 0.77 to 1.22). Among the remaining 6,231 patients with 2 to 4 NOD risk factors, NOD developed in 448 of 3,128 in the atorvastatin 80 mg group and in 368 of 3,103 in the lower-dose groups (14.3% vs. 11.9%; HR: 1.24; 95% CI: 1.08 to 1.42; p = 0.0027). The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups.

Conclusions:  Compared with lower-dose statin therapy, atorvastatin 80 mg/day did not increase the incidence of NOD in patients with 0 to 1 NOD risk factors but did, by 24%, among patients with 2 to 4 NOD risk factors. The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups.

COMMENT: This is a sub-analysis of the Jupiter study specifically looking at the effect of increasing doses of atorvastatin on new onset diabetes as a function of diabetes risk factors.  In the absence of diabetes risk factors or in the presence of only one such risk factor, there was no relationship between the dose of the statin and the development of new-onset diabetes.  In the presence of two or more risk factors there was a dose effect with the higher doses having an increase of 24% more than with those with 0 or 1 risk factor.  In all instances the atorvastatin groups had a significantly reduced number of cardiovascular events.  This study should help us put in perspective the risk of the development of diabetes with statin therapy in individual patients.