Lisinopril - A review of its use in congestive heart failure

The ACE inhibitor lisinopril is a lysine derivative of enalaprilat, the act ive metabolite of enalapril. In patients with heart failure, maximum pharma codynamic effects are produced 6 to 8 hours after administration of the dru g and persist for 12 to 24 hours. High doses (32.5 to 35mg, administered once daily) of lisinopril in the Ass essment of Treatment with Lisinopril and Survival (ATLAS) study demonstrate d clinically important advantages over low doses (32.5 to 35mg, administere d once daily) of the drug in the treatment of congestive heart failure. Hig h doses of lisinopril were more effective than low doses in reducing the ri sk of major clinical events in patients with heart failure treated for 39 t o 58 months. Compared with recipients of low doses, those receiving high do ses of lisinopril had an 8% lower risk of all-cause mortality (p = 0.128), a 12% lower risk of death or hospitalisation fur any reason (p = 0.002) and 24% fewer hospitalisations for heart failure (p = 0.002). These benefits w ere associated with significant cost savings. In short term (generally 12 weeks' duration) randomised, double-blind, para llel-group, multicentre clinical trials, lisinopril was significantly more effective than placebo and was at least as effective as captopril, enalapri l, digoxin and irbesartan at improving symptomatic end-points and clinical status in patients with heart failure. Lisinopril is generally well tolerated by patients with heart failure. In c ontrolled clinical trials, the most common adverse events occurring in reci pients of the drug were dizziness, headache, hypotension and diarrhoea. Ove rall adverse event profiles for patients treated with high or low doses of lisinopril in the ATLAS study were similar. However, high doses of lisinopr il used in the ATLAS study were associated with a higher incidence of adver se events, importantly hypotension and worsening renal function; neverthele ss, these events were generally well managed by altering the dose of lisino pril or concomitant medications. Further more, despite the higher incidence of some adverse events with high doses of lisinopril, the frequency of tre atment discontinuations because of adverse events was the same in the high and low dose groups. Conclusions: Lisinopril (when added to diuretics and/or digoxin) provides s ymptomatic benefits in patients with congestive heart failure. The ATLAS st udy demonstrated that high doses of lisinopril significantly reduced the ri sk of the combined end-point of morbidity and mortality compared with low d oses of the drug. importantly, there was no clinically significant decrease in the tolerability of the drug with use of a high dose. Lisinopril is at least as effective and as well tolerated as other members of the ACE inhibi tor class for the treatment of congestive heart failure.