ACE inhibitors may be of benefit in atherosclerosis

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The Pharmaceutical Journal
Vol 277 No 7414 p213
19 August 2006

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ACE inhibitors may be of benefit in atherosclerosis

BSIP VEM/Science Photo Library

Atherosclerosis

Atherosclerosis: a slice through an artery showing a thick deposit of atheroma

Angiotensin-converting enzyme (ACE) inhibitors should be considered for all patients with atherosclerosis, including those with no history of heart failure or left ventricular systolic dysfunction (LVSD), according to the authors of a recent study (Lancet 2006;368:581). However, commentators argue that only high-risk patients will benefit.

Gilles Dagenais, Laval Hospital, Quebec, and colleagues combined the findings of three trials — known as HOPE, EUROPA and PEACE — involving just under 30,000 patients who had been randomly assigned to an ACE inhibitor or placebo and followed up for an average of 4.5 years. Overall, the data indicate that use of ACE inhibitors reduces some of the most serious circulatory problems in stable patients with no history of heart failure or LVSD (see Panel below).

Findings from the combined analysis

In the combined analysis of the HOPE (heart outcomes prevention evaluation), EUROPA (European trial on reduction of cardiac events with perindopril among patients with stable coronary artery disease) and PEACE (prevention of events with angiotensin-converting enzyme inhibition) trials, all-cause mortality was reduced (7.8 per cent versus 8.9 per cent, P=0.0004) as were cardiovascular mortality (4.3 per cent versus 5.2 per cent, P=0.0002), non-fatal myocardial infarction (5.3 per cent versus 6.4 per cent, P=0.0001), all stroke (2.2 per cent versus 2.8 per cent, P=0.0004), heart failure (2.1 per cent versus 2.7 per cent, P=0.0007) and need for coronary artery bypass surgery (6.0 per cent versus 6.9 per cent, P=0.0036).

Disagreement has been expressed over conclusions drawn from the PEACE trial — since results from this study differ from the other two. (In the PEACE trial, the ACE inhibitor used did not significantly reduce cardiovascular events and all-cause mortality.) The original study investigators attribute these differences to the lower risk their patients had for cardiovascular events and the higher proportion of their patients taking lipid-lowering agents, antiplatelets and beta blockers. By contrast, the authors of the combined analysis suggest that the PEACE trial was inadequately powered to detect moderate differences on spontaneously occurring clinical outcomes.They conclude: “Use of ACE inhibitors should be considered in all patients with vascular disease as long as they can tolerate these agents and the absolute benefits are judged to be valuable.”

The authors of an accompanying editorial disagree (ibid, p555). Giuseppe Remuzzi and Piero Ruggenenti, of the Riuniti Hospital, Bergamo, Italy, suggest the data only show that ACE inhibitors are of value for high-risk patients with diabetes and for those whose serum lipid concentrations are not controlled. “ACE inhibitors do not offer added benefit to low-risk patients already on aspirin, beta blockers and statins,” they say.