Fosinopril. A Review of Its Pharmacology and Clinical Efficacy in the Management of Heart Failure

Fosinopril is the prodrug of the active diacid ACE inhibitor fosinoprilat. In patients with heart failure, fosinopril reduces pulmonary capillary wedge pressure, mean arterial blood pressure, mean right atrial pressure and heart rate, and increases stroke volume index and cardiac index. The drug has compensatory dual elimination routes via renal and hepatic systems and accumulates to a lesser extent than enalapril and lisinopril in patients with chronic renal insufficiency with or without heart failure. Comparative studies of 3 or 6 months' duration with fosinopril 10 to 40 mg/day have demonstrated clinical efficacy significantly superior to that of placebo in patients with heart failure [mostly New York Heart Association (NYHA) functional class II or III]. Fosinopril treatment consistently increased exercise duration and improved heart failure symptoms in these patients. Significantly fewer fosinopril than placebo recipients withdrew or were hospitalised because of worsening heart failure. Additionally, significantly more fosinopril than placebo recipients showed improvement, and fewer patients had deteriorated, in terms of NYHA functional class. Fosinopril and enalapril showed similar clinical efficacy over 6 and 12 months' treatment in patients with NYHA functional class II to IV heart failure. As yet, there are no data showing a mortality benefit with fosinopril. Fosinopril was well tolerated in clinical trials in patients with heart failure. Dizziness (11.9 vs 5.4% for placebo), cough (9.7 vs 5.1%) and hypotension (4.4 vs 0.8%) were the most commonly reported adverse events. In 6- or 12-month comparative studies, fosinopril therapy was associated with a lower incidence of dizziness and hypotension, but a higher incidence of vertigo, than enalapril therapy. 0.8% of patients discontinued the drug because of cough, which occurred to a similar extent with fosinopril and enalapril. Thus, based on available clinical evidence, fosinopril is an effective and well tolerated option for the management of patients with heart failure. Although clinical data are limited, fosinopril may be especially useful in patients with renal or hepatic impairment.