QUINAPRIL - A REAPPRAISAL OF ITS PHARMACOLOGY AND THERAPEUTIC EFFICACY IN CARDIOVASCULAR DISORDERS

Following systemic absorption, quinapril is converted by de-esterifica tion to quinaprilat (the active diacid metabolite), an inhibitor of an giotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of quinapril. T issue ACE inhibition may be an important component of the mechanism of action of quinapril (and other ACE inhibitors) in achieving favourabl e effects in cardiovascular disorders. Quinaprilat has a short elimina tion half-life (approximate to 2 hours), but binds potently to and dis sociates slowly from ACE, thus allowing once or twice daily administra tion of quinapril in the treatment of patients with hypertension or co ngestive heart failure. Quinapril 10 to 40 mg/day has achieved adequat e control of blood pressure in most patients with essential hypertensi on in clinical trials. Some patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic therapy. Titrating quinapril dos ages from 10 to 40 mg/day increased response rates without increasing the incidence ol severity of adverse events. Addition of hydrochloroth iazide to quniapril therapy improved response rates by approximately 1 0 to 20% in patients with hypertension. In general, blood pressure con trol with quinapril monotherapy was similar to that achieved with enal april or other standard antihypertensive agents in comparative trials. Quinapril less than or equal to 40 mg/day improved exercise tolerance , reduced the severity and frequency of symptoms, and improved functio nal (New York Heart Association) class in most clinical studies of pat ients with congestive heart failure. In addition, beneficial haemodyna mic and echocardiographic changes achieved with quinapril were maintai ned for up to 1 year with continued administration to such patients, b ut its effect on survival in patients with congestive heart failure ha s not been reported. The tolerability profile of quinapril is broadly similar to that of other ACE inhibitors: pooled data from clinical tri als indicated that 12% of patients with hypertension or congestive hea rt failure receiving quinapril experienced a treatment-related adverse effect compared with 15% of enalapril recipients and 16% of captopril recipients. Thus, quinapril has clearly established a role as an effe ctive and well tolerated alternative to other ACE inhibitors for the t reatment of hypertension and congestive heart failure. While effects o f quinapril on survival of patients with congestive heart failure have not been determined, large intervention studies have demonstrated imp roved mortality rates with other ACE inhibitors. Further studies, incl uding a large ongoing trial of normotensive patients with coronary art ery disease but normal left ventricular function, may also establish a role for quinapril in treating patients with ischaemic heart disease.