Czech and Slovak spirapril intervention study (CASSIS). A randomized, placebo and active-controlled, double-blind multicentre trial in patients with congestive heart failure.

A randomized, double-blind, placebo- and active-controlled multicentre study with spirapril, a new angiotensin-converting enzyme inhibitor (ACEI), has been conducted in patients with chronic congestive heart failure (CHF) of NYHA classes II-IV. After a placebo run-in period of 1-4 weeks, patients were randomly assigned to one of five treatment groups: placebo (n = 48), spirapril 1.5 mg (n = 48), spirapril 3 mg (n = 53), spirapril 6 mg (n = 51) or enalapril 5/10 mg (n = 48). The primary objective was to assess changes in exercise tolerance, and the secondary objective was an assessment of cardiovascular signs and symptoms, quality of life, ejection fraction and chest X-ray findings. Exercise tolerance increased in all groups; however, no statistically significant differences were found between any of the groups. There was a statistically significant reduction of mortality in the pooled spirapril groups compared with placebo, and a trend for reduction of serious cardiovascular adverse events as well as duration of hospitalization. These effects and improvements in lung congestion appeared to be dose dependent. In patients with moderate to severe heart failure, the combination with first-generation calcium channel blockers had an unfavourable effect on exercise capacity and clinical parameters. Spirapril might be an effective alternative to enalapril in the treatment of patients with CHF. The role of the exercise tolerance test in establishing efficacy of ACEIs in CHF and the widespread use of nifedipine in CHF is questioned.