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ACE inhibitor attenuates risk of beta blocker associated diabetes

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Cotreatment with an angiotensin-converting enzyme (ACE) inhibitor reduces the risk of diabetes associated with beta blocker treatment, according to a report in the April 18th online American Journal of Cardiology.

“Clinicians should evaluate the totality of metabolic risk portended by anti-hypertensive agents and consider using combination therapies that minimize potential adverse outcomes,” Dr. Orly Vardeny from University of Wisconsin School of Pharmacy, Madison, Wisconsin told Reuters Health by email. “We rarely use single drug blood pressure lowering regimens; therefore, the effects, both negative and positive, of combination therapies should be weighed ahead of time and individually optimized based on the patient’s risk factors.”

Dr. Vardeny and colleagues in the Prevention of Events with an ACE Inhibitor (PEACE) trial investigated the influence of beta blockers on the risk for new-onset diabetes and whether this risk is modified by ACE inhibition with trandolapril in a randomized study of 6910 patients, 4147 of which were taking beta blockers.

“This was a post-hoc analysis of a clinical trial,” Dr. Vardeny said, “and it is important to note that beta blocker use was not blinded.”

Over the 4.8 years of the trial, there were 733 cases of new-onset diabetes.

Beta blocker use was associated with a 36% increased risk for new-onset diabetes after adjustment for other factors, whereas randomization to trandolapril was associated with a 17% decreased risk for new-onset diabetes.

There was a significant interaction between beta blocker and trandolapril treatment: 2090 patients taking beta blockers and placebo faced a 63% increased risk for new-onset diabetes, whereas 2057 patients taking beta blockers and trandolapril had a nonsignificant 11% increased risk for new-onset diabetes.

In fact, the researchers note, the benefit of the ACE inhibitor with respect to new-onset diabetes seen in PEACE was essentially limited to patients taking beta blockers.

Results were similar in propensity-adjusted analyses.

“I would be cautious in using a beta blocker by itself in individuals with metabolic syndrome as a single agent for hypertension, and may choose an ACE inhibitor or angiotensin receptor blocker (ARB) instead,” Dr. Vardeny said.

“Beta blockers are, however, life-saving therapies for certain indications, such as to prevent post-MI remodeling and for patients with systolic dysfunction heart failure,” Dr. Vardeny explained. “In those cases, avoiding a beta blocker should not be an option. The good news is that for those conditions, an ACE inhibitor is also indicated concomitantly, and as such the negative metabolic effect of the beta blocker could be attenuated by the ACE inhibitor.”

“We’d like to further explore the interrelationships between the renin-angiotensin-aldosterone (RAAS) and the sympathetic nervous system (SNS) in patients with diabetes,” Dr. Vardeny added. “We are currently examining metabolic effects of aldosterone antagonists and direct renin inhibitors when used in combination regimens in patients with hypertension and heart failure. Additionally, we are investigating pharmacogenetic associations between beta adrenergic receptor genetic variants and polymorphisms of the RAAS and metabolic outcomes in patients taking beta blockers, ACE inhibitors, ARBs, and direct renin inhibitors.”

Am J Cardiol 18 April 2011.