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Czech and Slovak spirapril intervention study (CASSIS)

A randomized, placebo and active-controlled, double-blind multicentre trial in patients with congestive heart failure

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Abstract

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.

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References

  1. Acute Infarction Ramipril Efficacy (AIRE) Study Investigators (1993) Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 342:821–828

    Google Scholar 

  2. Captopril-Digitalis Research Group (1988) Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. JAMA 259:539–544

    Google Scholar 

  3. Captopril Multicentre Research Group (1983) A placebo-controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol 63:755–763

    Google Scholar 

  4. Chalmers JP, West MJ, Cyran J, De La Torre D, Englert M et al. (1987) Placebo-controlled study of lisinopril in congestive heart failure: a multicenter study. J Cardiovasc Pharmacol 9 [Suppl 3]:S89-S97

    Google Scholar 

  5. Cleland JGF, Henderson E, McLenachan J, Findlay IN, Dargie HJ (1991) Effect of captopril in patients with angina pectoris and heart failure. J Am Coll Cardiol 17:733–739

    Google Scholar 

  6. Cohn J, Johnson G, Ziesche S et al. (1991) A comparison of enalapril with hydralazine/isosorbide dinitrate in the treatment of chronic congestive heart failure (V-HeFT II). N Engl J Med 325:303–310

    Google Scholar 

  7. CONSENSUS Trial Study Group (1987) Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 316:1429–1435

    Google Scholar 

  8. DiBianco R (1990) ACE inhibitors in the treatment of heart failure. Clin Cardiol 13:VII-32–38

    Google Scholar 

  9. Elkayam U, Anim J, Mehra A, Vasquez J, Weber L et al. (1990) A prospective, randomized double-blind, crossover study to compare efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation 82:1954–1961

    Google Scholar 

  10. Enalapril Congestive Heart Failure Investigators (1987) Long-term effects of enalapril in patients with congestive heart failure: a multicentre, placebo-controlled trial. Heart Failure Jun/Jul 102–107

  11. Francis GS (1991) Calcium channel blockers and congestive heart failure. Circulation 83:336–338

    Google Scholar 

  12. Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S (1991) Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation 83:52–60

    Google Scholar 

  13. Grass P, Gerbeau C, Kutz K (1994) Spirapril pharmacokinetic properties and drug interactions. Blood Pressure 3 [Suppl 2]:7–13

    Google Scholar 

  14. Jerie P, Kremer HJ (1992) Renpress®, Sandopril® (Spirapril/TI 211–950) — Summary of chemical, pharmacological and clinical properties. Cor Vasa 34:82–87

    Google Scholar 

  15. Just J, Drexler H, Taylor SH, Siegrist J, Schulgen G, Schumacher M, for the CADS Study Group (1993) Captopril versus digoxin in patients with coronary artery disease and mild heart failure. Herz 18 [Suppl 1]:443–446

    Google Scholar 

  16. Meredith PA, Grass P, Guitard C, Elliott HL (1994) Pharmacokinetics of spirapril in renal impairment. Blood Pressure 1 [Suppl 1]:14–20

    Google Scholar 

  17. Newman TJ, Maskin CS, Dennick LG, Meyer JH, Hallows BG, Cooper WH (1988) Effects of captopril on survival in patients with heart failure. Am J. Med 84 [Suppl 3a]:140–144

    Google Scholar 

  18. Packer M (1989) Therapeutic options in the management of chronic heart failure: is there a drug of first choice? (editorial). Circulation 79:198–199

    Google Scholar 

  19. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E (1988) Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 319:80–86

    Google Scholar 

  20. Pfeffer MA, Braunwald E, Moyé LA et al. (1992) Effects of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial (SAVE). N Engl J Med 327:669–677

    Google Scholar 

  21. Pflugfelder PW, Baird MG, Tonkon MJ, DiBianco R, Pitt B for the Quinapril Heart Failure Trial Investigators (1993) Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. J Am Coll Cardiol 22: 1557–1563

    Google Scholar 

  22. Rector TS, Kubo SH, Cohn JN (1987) Patients' self-assessment of their congestive heart failure: part 2. Content, reliability and validity of a new measure, the Minnesota Living with Heart Failure Questionnaire. Heart Failure 3:198–209

    Google Scholar 

  23. Rucinska EJ (1991) Enalapril in the treatment of congestive heart failure: effects on signs, symptoms and mortality. Acta Cardiol 46:237–246

    Google Scholar 

  24. Sharpe DN, Murphy J, Coxon R, Hannan SF (1984) Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study. Circulation 70:271–278

    Google Scholar 

  25. SOLVD investigators (1991) Effects of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 325:293–302

    Google Scholar 

  26. SOLVD investigators (1992) Effects of enalapril on mortality and development of heart failure in asymptomatic patients with reduced left ventricular ejection fraction. N Engl J Med 327:685–691

    Google Scholar 

  27. Špinar J, Vítovec J, Blaha M, Štejfa M, Toman J, Špinarová L, Pličzka Z (1992) Radiological changes in chronic congestive heart failure. Cor Vasa 18:88–99

    Google Scholar 

  28. Swedberg K, Amtorp O, Gundersen T, Remes J, Nilsson B (1991) Is maximal exercise testing a useful method to evaluate treatment of moderate heart failure? (abstr.) Circulation 84 [Suppl II]:II-57

  29. Swedberg K, Held P, Kjekshus J, Rasmussen K, Rydén L, Wedel H (1992) Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 327:678–684

    Google Scholar 

  30. Sybertz EJ, Watkins RW, Ahn HS, Baum T, La Rocca P, Patrick J, Leitz F (1987) Pharmacologic, metabolic and toxicologic profile of spirapril (SCH 33844), a new angiotensin converting enzyme inhibitor. J Cardiovasc Pharmacol 10 [Suppl 7]: S105

  31. van den Broek S, van Bruggen A, de Graeff P, Hillege H, van Gilst W, Wesseling H, Lie KI (1991) The acute haemodynamic, hormonal and pharmacokinetic properties of oral spirapril in patients with moderate to severe heart failure. J Cardiovasc Pharmacol 18:614–621

    Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, IPVZ, 800 Videňská, CZ-14622, Prague, Czech Republic

    J. Widimský & O. Uhlíř

  2. Sandoz Pharma AG, Basel, Switzerland

    H. J. Kremer & P. Jerie

Authors
  1. J. Widimský
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  2. O. Uhlíř
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  3. H. J. Kremer
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  4. P. Jerie
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Widimský, J., Uhlíř, O., Kremer, H.J. et al. Czech and Slovak spirapril intervention study (CASSIS). Eur J Clin Pharmacol 49, 95–102 (1995). https://doi.org/10.1007/BF00192366

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  • DOI: https://doi.org/10.1007/BF00192366

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