Secondary Prevention of Coronary Disease with ACE Inhibition-does Blood Pressure Reduction with Perindopril Explain the Benefits in EUROPA?

We determined whether blood pressure (BP) lowering by perindopril was related to its benefit in the EUROPA study. Twelve thousand two hundred eighteen patients with documented coronary artery disease received perindopril 8 mg once daily or matching placebo after a 4-week run-in period in which all patients received perindopril. Patients were excluded if systolic (S) BP was > 180 or < 100 mmHg. Mean age was 60 years (range 26-89). 27% had a history of hypertension. After 4.2 years of follow-up, the primary endpoint (cardiovascular death, nonfatal myocardial infarction, or resuscitated cardiac arrest) was observed in 603 (9.9%) placebo versus 488 (8.0%) perindopril patients [20% relative risk reduction (RRR), CI 9-29%, P = 0.003]. There was no interaction between baseline SBP levels (using JNC-7 cutoff values) and treatment effect. If anything, the greatest RRR of the primary endpoint (32%) occurred in patients with the lowest SBP (< 120 mmHg) in whom perindopril did not reduce SBP. Also, RRR during blinded treatment was comparable, irrespective of whether BP decreased or not or of the extent of BP reduction during perindopril treatment. The treatment benefit in EUROPA cannot be fully explained by baseline BP or BP reduction with perindopril. Other mechanisms including direct anti-atherosclerotic effects of ACE inhibition may play a role.