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.