Recent Cardiovascular Studies
The EUROPA (EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease) trial studied the effects of perindopril, a long-acting ACE inhibitor, on cardiovascular events in 12,218 male and female patients with documented history of coronary artery disease but no clinical evidence of heart failure.[10] Over a mean follow-up of 3.7 years there was a 20% relative risk reduction in the composite primary end point of cardiovascular death, non-fatal MI and successfully resuscitated cardiac arrest ( table 1 ), (p=0.0003).
The PERSUADE (PERindopril SUbstudy in coronary Artery DiseasE and diabetes) study is due to be published in the near future and reports the results of the 1,502 subjects who had diabetes at time of entry into EUROPA.[11] The relative risk reduction with perindopril on primary and secondary end points was similar to that in the main EUROPA population but as there was a higher event rate in diabetic patients, the absolute risk reduction was greater.
The 'number needed to treat' (NNT) was more favourable for diabetic patients. To prevent one cardiovascular death or non-fatal MI, 27 diabetic patients would need to be treated for four years, as opposed to 40 patients in the main study cohort. In addition, as in non-diabetic subjects, the protective effects of perindopril were independent of blood pressure at baseline, and independent of the blood pressure reduction achieved by the drug, suggesting that perindopril may exert its protective effect via other mechanisms e.g. accumulation of bradykinin, or improvements in endothelial function.
The PEACE (Prevention of Events with Angiotensin Converting Enzyme Inhibition) trial compared the effects of placebo versus trandolapril on the prevention of cardiovascular events in a cohort of 8,290 patients (17% of whom had diabetes) with established cardiovascular disease and normal or only slightly reduced left ventricular function.[12] Surprisingly, there were no significant reductions in cardiovascular end points, which contrasts to the HOPE and EUROPA studies. There are several possible explanations for this. The PEACE patients were at lower risk of cardiovascular events than patients in previous studies; there were fewer events during the trial from which to draw conclusions. Secondly, two years before PEACE finished the steering committee advised the investigators to substitute open-label ACE inhibitors for the masked study treatment in patients with diabetes and either overt proteinuria or hypertension and microalbuminuria. This dilutes the treatment effect within the trial. Thirdly, patient compliance and dose achievement was not as good in PEACE as in EUROPA and HOPE. One positive finding in PEACE was a reduction in the onset of new diabetes in the trandolapril group, as has been seen in several other trials with ACE inhibitors and ARBs.[13]
The LIFE (Losartan Intervention For Endpoint reduction in hypertension) study compared the effects of losartan versus atenolol-based treatment on cardiovascular morbidity and mortality. Losartan exerts potential beneficial effects not only via its antihypertensive properties but also as a result of its blockade of angiotensin II. For example, this should have a greater benefit on regression of left ventricular hypertrophy.[14] The LIFE study demonstrated a 13% relative risk reduction in the composite primary end point of cardiovascular death, MI and stroke. There were no significant reductions in MI, but a highly significant relative risk reduction of 24.9% in the incidence of stroke in the losartan-treated group over the mean follow-up of 4.8 years. The results from the LIFE diabetes subgroup of 1,195 individuals were published separately[15] and were even more dramatic. In subjects with diabetes, treatment with losartan caused a 5% reduction in the composite end point compared to atenolol, whereas a 2% reduction was observed in the overall study. Significant reductions were seen in cardiovascular and total mortality compared to atenolol, but reductions in stroke and myocardial infarction were not significant.
Br J Cardiol. 2005;12(2):130-134. © 2005 Sherborne Gibbs Ltd.
Cite this: Should All Diabetic Patients Receive an ACE Inhibitor? Results From Recent Trials - Medscape - Mar 01, 2005.
