The mean age of patients was 60 years; 85% were male, 92% were taking platelet inhibitors, 63% were taking β blockers, and 56% were taking lipid-lowering therapy. The EUROPA study showed that perindopril significantly reduced the relative risk for the primary endpoint events (Table 1). This beneficial effect is largely attributable to a reduction in the risk of nonfatal myocardial infarction. This beneficial effect of perindopril on the primary outcome was evident after about one year of treatment (Figure 1).

Table 1. Primary Endpoint and Relative Risk Reduction

The outcome was similar across all predefined subgroups by age, underlying disease or concomitant medication (Figure 2).

Figure 1. Time to First Occurrence of Primary Endpoint

Figure 2. Beneficial Effect of Perindopril Treatment on Primary Endpoint in Predefined Subgroups

Size of squares proportional to the number of patients in that group. Dashed line indicates overall relative risk.

Hypertension

In placebo-controlled studies of perindopril monotherapy (2 to 16 mg q.d.) in patients with a mean blood pressure of about 150/100 mm Hg, 2 mg had little effect, but doses of 4 to 16 mg lowered blood pressure. The 8 and 16 mg doses were indistinguishable, and both had a greater effect than the 4 mg dose. The magnitude of the blood pressure effect was similar in the standing and supine positions, generally about 1 mm Hg greater on standing. In these studies, doses of 8 and 16 mg per day gave supine, trough blood pressure reductions of 9 to 15/5 to 6 mm Hg. When once-daily and twice-daily dosing were compared, the B.I.D. regimen was generally slightly superior, but by not more than about 0.5 to 1 mm Hg. After 2 to 16 mg doses of perindopril, the trough mean systolic and diastolic blood pressure effects were approximately equal to the peak effects (measured 3 to 7 hours after dosing.). Trough effects were about 75 to 100% of peak effects. When perindopril was given to patients receiving 25 mg HCTZ, it had an added effect similar in magnitude to its effect as monotherapy, but 2 to 8 mg doses were approximately equal in effectiveness. In general, the effect of perindopril occurred promptly, with effects increasing slightly over several weeks.

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