Opposing Effects of β-Blockers and Angiotensin-Converting Enzyme Inhibitors on Development of New-Onset Diabetes Mellitus in Patients With Stable Coronary Artery Disease

Study Questions:

What is the risk of new-onset diabetes mellitus (NOD) with beta-blockers, and would angiotensin-converting enzyme (ACE) inhibition modify this risk?

Methods:

The PEACE trial randomized 8,290 patients with stable coronary artery disease (CAD) to trandolapril or placebo. Presence of NOD was assessed at each study visit over a median follow-up of 4.8 years. The authors examined the risk of NOD associated with beta-blocker use with Cox regression models adjusting for 25 baseline covariates, and tested whether this risk was modified by randomization to the ACE inhibitor.

Results:

Of 6,910 patients without diabetes mellitus at enrollment (1,179 women and 5,731 men, mean age 64 ± 8 years), 4,147 (60%) were taking beta-blockers and 733 (8.8%) developed NOD. There was a significant interaction between beta-blocker use and randomization to ACE inhibitor with respect to NOD (p = 0.028). Participants taking beta-blockers assigned to the placebo group (n = 2,090) were at increased risk for NOD adjusting for baseline covariates (hazard ratio, 1.63; 95% confidence interval, 1.29-2.05; p < 0.001), and this risk was attenuated in those assigned to trandolapril (n = 2,057; hazard ratio, 1.11; 95% confidence interval, 0.87-1.42; p = 0.39). Beta-blocker use was associated with increased risk for NOD in patients with stable CAD, and this risk was decreased in patients treated concurrently with an ACE inhibitor.

Conclusions:

The authors concluded that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking beta-blockers.

Perspective:

This study suggests that in patients with stable CAD, use of beta-blockers was associated with an increased risk for development of NOD in traditional, propensity-adjusted, and time-dependent analyses. Furthermore, there was a significant interaction between ACE inhibitor treatment assignment and beta-blocker use with respect to NOD risk such that the risk for NOD associated with beta-blockers was attenuated in participants randomized to an ACE inhibitor. These data have clinical relevance in a high-risk population of patients taking multiple medications who are potentially at risk for development of diabetes.

Clinical Topics: Statins

Keywords: Coronary Artery Disease, Follow-Up Studies, Indoles, Diabetes Mellitus


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