Perindopril: an updated review of its use in hypertension.
Perindopril erbumine (perindopril) is a prodrug ester of perindoprilat, an angiotensin converting enzyme (ACE) inhibitor. Perindopril 4 to 8 mg once daily significantly reduces supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline values in hypertensive patients. These reductions are maintained for at least 24 hours, as evidenced by trough/peak ratios of >50%. Vascular abnormalities associated with hypertension were improved or normalised during perindopril treatment. Perindopril 4 to 8 mg once daily significantly decreased carotid-femoral aortic pulse wave velocity (PWV), improved arterial compliance, reduced left ventricular mass index and, in patients with recent cerebral ischaemia and/or stroke, preserved cerebral blood flow despite significantly reducing SBP and DBP. Further research is needed to establish the significance of promising results showing that reductions in aortic PWV were associated with reduced mortality in patients with end-stage renal failure, a third of whom received perindopril. Response rates (numbers of patients with supine DBP < or = 90 mm Hg) were significantly higher with perindopril 4 to 8 mg once daily (67 to 80%) than with captopril 25 to 50 mg twice daily (44 to 57%) in 3 randomised double-blind trials. In other clinical trials, the antihypertensive effects of perindopril were similar to those of other ACE inhibitors (including enalapril) and calcium-channel antagonists. Combination treatment with perindopril and an antihypertensive agent from another treatment class provided additional benefits, either as first-line treatment or in patients failing to respond to monotherapy. Perindopril monotherapy was also effective in the elderly and in patients with hypertension and concomitant disease. Perindopril has a similar adverse event profile to that of other ACE inhibitors; cough is the most common event reported during treatment, and is also the most common adverse event responsible for treatment withdrawal.


CONCLUSIONS
Perindopril is a well tolerated ACE inhibitor that is significantly better than captopril (in terms of response rates) in the treatment of hypertension, and as effective as other ACE inhibitors. Perindopril appears to reverse some of the vascular abnormalities associated with hypertension, including arterial stiffness and left ventricular hypertrophy, although further research is needed to confirm promising results regarding its ability to decrease associated cardiovascular morbidity and mortality. Results from ongoing studies will help confirm the place of perindopril in the treatment of hypertension; currently, it is an effective and well tolerated treatment for patients with mild to moderate essential hypertension.
Hurst
M
M
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Jarvis
B
B
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D005342:Fibrinolysis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D020913:Perindopril / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D020913:Perindopril