Quinapril is rapidly de-esterified after absorption to
quinaprilat (the active diacid metabolite), a potent
angiotensin converting enzyme (
ACE) inhibitor.
Quinapril produces favourable haemodynamic changes, and improves ventricular and endothelial function in patients with various cardiovascular disorders; these effects are mediated through the binding of
quinaprilat to both tissue and plasma ACE.
Quinapril 10 to 40 mg/day provided effective blood pressure control in most patients with
essential hypertension in clinical trials, but some patients required dosages of 80 mg/day and/or concomitant
diuretic therapy. In general,
quinapril provided similar blood pressure control to other standard
antihypertensive therapies including other
ACE inhibitors,
calcium antagonists and
beta-adrenoceptor antagonists in comparative clinical trials. Combined
therapy with
quinapril and
hydrochlorothiazide had a significantly greater
antihypertensive effect than either
drug as monotherapy in two well designed studies.
Quinapril has also been shown to reduce microalbuminuria in patients with
hypertension and/or
diabetes mellitus. In patients with
congestive heart failure,
quinapril <or=40 mg/day produced beneficial haemodynamic and echocardiographic changes and improved exercise tolerance, symptoms and functional class. Effects of
quinapril on survival have not been investigated, but
quinapril 10 to 20 mg/day showed comparable efficacy to
captopril 25 to 50mg twice daily in two well designed trials. In patients with
coronary artery disease,
quinapril 40 mg/day significantly reduced the incidence of ischaemic events after
coronary artery bypass grafting (CABG) in a well controlled study (n = 148). However, a lower dosage of
quinapril (20 mg/day) showed no effect on ischaemic events or atherosclerotic progression with 3 years of treatment in a similarly designed study involving 1750 patients undergoing coronary angioplasty. The tolerability of
quinapril is similar to that of other
ACE inhibitors. In placebo-controlled trials,
cough occurred in 2 and 4.3% and
hypotension occurred in <1 and 2.9% of
quinapril recipients with
hypertension or
congestive heart failure, respectively. No increase in adverse events was observed when the dosage was increased from 10 to 40 mg/day.
CONCLUSION:
Quinapril is now firmly established as an effective and well tolerated
ACE inhibitor for the treatment of patients with
hypertension and
congestive heart failure.
Quinapril 40 mg/day also significantly reduced the incidence of ischaemic events in patients undergoing CABG in one study; however, a lower dosage of
quinapril (20 mg/day) had no effect on ischaemic events in patients undergoing coronary angioplasty in another trial. Additional trials in patients with
coronary artery disease receiving optimal dosages of
quinapril (40 mg/day) would be useful.