Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders.
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.


CONCLUSIONS
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.
Culy
Christine R
CR
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Jarvis
Blair
B
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D000077583:Quinapril; D016032:Randomized Controlled Trials as Topic; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D011355:Prodrugs; D044005:Tetrahydroisoquinolines; D000077583:Quinapril