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[A Czech and Slovak interventional study of spirapril (the CASSIS study). A randomized, double-blind, multicenter,
Insights
Spirapril, an ACE-inhibitor, demonstrated reduced mortality and hospital admissions in chronic heart failure patients. While load tolerance showed no significant group differences, spirapril effectively treated cardiac symptoms and reduced heart size.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic symptomatic heart failure (NYHA II-IV) requires effective treatment.
- Existing therapies like digoxin and diuretics may not suffice for all patients.
- ACE-inhibitors are crucial in managing heart failure.
Purpose of the Study:
- To evaluate the efficacy and safety of spirapril, a novel ACE-inhibitor, in patients with chronic symptomatic heart failure.
- To assess spirapril's impact on exercise tolerance, cardiac symptoms, and overall survival.
Main Methods:
- A randomized, double-blind, multicentric study involving 248 patients with chronic heart failure.
- Patients received placebo or varying doses of spirapril (1.5-10 mg) for 12 weeks after an initial placebo phase.
- Primary endpoint was exercise load tolerance; secondary endpoints included cardiac symptoms, left ventricular ejection fraction, and mortality.
Main Results:
- Spirapril treatment led to a significant reduction in mortality and hospital admissions compared to placebo.
- Observed regression of pulmonary congestion and diminution of cardiac shadow in actively treated patients.
- No significant differences in exercise load tolerance were found between spirapril groups and placebo.
Conclusions:
- Spirapril, when combined with diuretics and digoxin, is a suitable treatment for chronic heart failure.
- Short-acting calcium channel blockers are not recommended for symptomatic chronic heart failure, especially with IHD.
- The clinical significance of loading tests for ACE-inhibitor efficacy requires further investigation.
Abstract:
Spirapril, an ACE-inhibitor without the SH group was tested in a randomized double-blind multicentric study in patients with chronic symptomatic heart failure (NYHA II-IV). After a 1-4-week initial stage with placebo the patients were randomized into five groups: the first was given placebo, the second one spirapril 1.5 mg, the third one spirapril 3 mg, the fourth one spirapril 6 mg and the fifth one 5 and later 10 mg for a period of 12 weeks. The number of patients in different groups was in the following order: 48, 48, 53, 51 and 48. The condition for admission into the study was chronic heart failure not responding adequately to treatment with digoxin and diuretics, IHD or dilatation cardiomyopathy with the left ventricular ejection fraction (% tolerating a basic ergometric load for two minutes. The primary criterium was an increment during the period of the load, secondary criteria comprised objective and subjective cardiac symptoms, changes in the left ventricular ejection fraction, cardiothoracic index/heart size and quality of life. The load tolerance increased in all groups, however, no significant differences between groups were found. The authors also found regression of signs of pulmonary congestion during active spirapril treatment and diminution of the cardiac shadow. Moreover the authors proved a significant reduction of the mortality in the actively treated patients as compared with those receiving placebo, a lower frequency of hospital admissions and reduction of serious undesirable cardiovascular symptoms during active treatment. In patients with medium severe and severe cardiac failure with IHD, combination with short acting calcium channel blockers had an unfavourable effect on the load tolerance and clinical parameters. Sprirapril, combined with diuretics and digoxin is a suitable drug also in chronic cardiac failure. Questionable remains the importance of loading tests when verifying the effectiveness of ACE-inhibitors. Treatment with short-time acting calcium antagonists cannot be recommended in symptomatic chronic cardiac failure.