Tolerance and safety of perindopril

Angiotensin converting enzyme inhibitors (ACEIs) constitute a safe and effective therapeutic class for the treatment of hypertension. However, they have been incriminated in the development of certain adverse effects, the most frequently reported being alteration in renal function, development of hypotension and cough. This justified the evaluation of renal function after short-term and long-term treatment with perindopril in hypertensive subjects. In patients with normal renal function, during short-term treatment (1 and 5 days), perindopril induced an increase in renal plasma flow without any modification of the glomerular filtration rate. During long-term administration (up to 18 months of treatment), no significant variation in plasma creatinine was observed. In elderly hypertensive patients or patients with chronic renal failure, the glomerular filtration rate was also preserved, apart from a few rare cases of decreased creatinine clearance, particularly after the addition of hydrochlorothiazide. A slight increase in plasma potassium, with no clinical significance, was observed when perindopril was used as single-agent therapy. Symptomatic hypotension was rarely reported with perindopril (0.2% of cases), even under conditions of salt and water depletion. Amongst the other adverse effects of ACEIs, cough, more recently identified, was investigated in detail. Its frequency was determined in a double-blind study comparing perindopril (1.2%) and captopril (2.4%). It was also evaluated in a long-term study in 632 hypertensive patients (391 treated for 1 year); its incidence was 2.9% and it was responsible for discontinuation of treatment in 8 cases. In this study, 36 patients stopped treatment prematurely because of an adverse effect (5.7%). No harmful drug interactions were reported. The combination of a thiazide diuretic potentiates the antihypertensive effect of perindopril and is perfectly tolerated. The favorable safety profile of perindopril should be related to the correct determination of effective doses.