ACE inhibitors supported for diabetic CAD

13 July 2005

The PERSUADE substudy of the EUROPA trial has provided further evidence that ACE inhibitors reduce the risk of cardiac events in patients with coronary artery disease (CAD), whether or not they have diabetes.

Although the 19% reduction in risk among patients with diabetes was not statistically significant compared with placebo, the researchers note that it is similar to the significant 20% relative risk reduction seen in the EUROPA trial.

In an editorial accompanying the study in the European Heart Journal, Canadian commentators led by Subodh Verma (University of Toronto, Ontario) say that clinicians must now recognize the important role of ACE inhibitors for vascular protection in high-risk diabetic patients.

"As echoed in the 2003 Canadian Diabetes Association guidelines, we believe the time has come to move away from a 'glucocentric' view of diabetes and PERSUADE physicians to protect the diabetic vasculature," they write.

The Perindopril Substudy of CAD in Diabetes (PERSUADE) was the diabetic substudy of the 12,218-patient European Trial on Reduction of Cardiac Events with Perindopril in Stable CAD (EUROPA) study.

Primary results from EUROPA, revealed at the 2003 European Society of Cardiology annual congress in Vienna, Austria, showed that patients treated with 8 mg perindopril daily on top of standard therapy were less likely to reach the primary endpoint of combined cardiovascular death, myocardial infarction, or cardiac arrest than those given placebo after 4.7 years, at 8% versus 9.9% (p=0.00033).

The PERSUADE analysis, first presented at the American College of Cardiology scientific sessions 2004 in New Orleans, Louisiana, revealed that the there was a nonsignificant reduction in the primary endpoint among the 1502 diabetic participants receiving perindopril instead of placebo, at 12.6% versus 15.5%, respectively (p=0.13).

Lead investigator Caroline Daly (Royal Brompton Hospital, London, UK) and colleagues conclude: "The results of PERSUADE are consistent with previous reports of beneficial cardiovascular effects of ACE inhibitors in the diabetic population.

"A statistically significant result was not obtained but the study did not have sufficient power to detect significant differences between the perindopril- and placebo-treated groups.

"Because the cardiovascular event rate in diabetics is higher than the general population with coronary disease, any relative reduction in events will translate into a greater absolute reduction, but direct evidence of additional benefit for diabetic patients compared with the overall population with coronary disease in relative terms has not been proven."

Eur Heart J 2005: 26: 1369-1378