The new drug is much more effective than ACE inhibitors in chronic heart failure

Česká verzia

Authors: Jiří Widimský Sr
Authors place of work: Klinika kardiologie IKEM Praha, přednosta prof. MUDr. Josef Kautzner, CSc.
Published in the journal: Vnitř Lék 2015; 61(2): 129-133
Category: Review

Summary

PARADIGM-HF study observed clinical outcomes after treatment by new drug LCZ696 or enalapril in patients with systolic chronic heart failure. It was randomized double-blind trial with LCZ696 (200 mg twice a day) and enalapril (10 mg twice a day). 8442 patients were enrolled with NYHA class II or III and left ventricular ejection fiction of 40% or less. Study drugs were added to other recommended medication. The trial was prematurely terminated after median follow-up of 27 months. The primary endpoint of the study was a combination of cardiovascular mortality and the first hospitalization for heart failure. LCZ696 drug, an inhibitor of angiotensin receptor and neprilysin (Arnie), has led to a reduction in the primary composite target by 20% (p <0.001). The treatment has decreased cardiovascular mortality by 20%, p <0.001 and hospitalization for worsening heart failure by 21%, p <0.001. LCZ696 has also decreased total mortality by 16%, p <0.001. The use of LCZ696 has been accompanied by frequent symptomatic hypotension and hypotension with a decrease in systolic blood pressure below 90 mm Hg, however, LCZ696 was less often associated with an increase in serum creatinine and serum potassium than enalapril. In addition, cough has occurred less frequently after LCZ696 than after enalapril. Discontinuation of therapy occurred in 746 patients (17.8%) treated with LCZ696 and in 833 patients (19.8%) treated with enalapril (19.8%) (p = 0.02). PARADIGM-HF study has also shown superiority of LCZ696 compared to ACE inhibitors in stable outpatients with chronic systolic heart failure NYHA stages II and III. Therefore, LCZ696 is more effective than ACE inhibitors (and angiotensin receptor blockers). Moreover, it is well tolerated. LCZ696 seems to replace the ACE inhibitors in mentioned patients. The authors also discuss the results of the first randomized study PARAMOUNT investigating LCZ696 efficacy in patients with chronic heart failure and good left ventricular ejection fraction.

Key words:
ARNi study – LCZ696 – PARADIGM – HF

Zdroje

1. McMurray JJV, Packer M, Desai AS et al. PARADIGM-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med 2014; 371(11): 993–1004.

2. Cohn JN, Archibald DG, Ziesche S et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986; 314(24): 1547–1552.

3. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).N Engl J Med 1987; 316(23): 1429–1435.

4. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 1991; 325(5): 293–302.

5. Cohn JN, Johnson G, Ziesche S et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991; 325(5): 303–310.

6. The SOLVD Investigators. Effect on enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992; 327(10): 685–691. Erratum in N Engl J Med 1992; 327(24):1768.

7. Cohn JN, and Tognoni G. Valsartan Heart Failure Trial Val-HeFT. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345(23): 1667–1675.

8. CIBIS Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353(9146): 9–13.

9. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure. Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353(9169): 2001–2007.

10. Packer M, Coats AJS, Fowler MB et al. Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001; 344(22): 1651–1658.

11. Pitt B, Zannad F, Remme WJ et al. Randomized Aldactone Evaluation Study Investigators. Effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341(10): 709–717.

12. Pitt B, Remme W, Zannad F et al. for the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348(14): 1309–1321.

13. Zannad F, McMurray JJ, Krum H et al. EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364(1): 11–21.

14. Digitalis Investigation Group. Effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336(8): 525–533.

15. Packer M, Califf RM, Konstam MA et al. Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation 2002; 106(8): 920–926.

16. Kostis JB, Packer M, Black HR et al. Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. Am J Hypertens 2004; 17(2): 103–111.

17. Ruilope LM, Dukat A, Böhm M et al. Blood pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo controlled, active comparator study. Lancet 2010; 375(9722): 1255–1266.

18. Jessup M. Neprilysin inhibition--a novel therapy for heart failure. N Engl J Med 2014; 371(11): 1062–1064.

19. Salomon SD, Zile M, Pieske B et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet 2012; 380(9851): 1387–1395.

20. Jhund PS, Claggett B, Packer M et al. Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial. Eur J Heart Fail 2014; 16(6): 671–677.

21. 21. Packer M, McMurray JJV, Desai AS et al (on behalf of the PARADIGM-HF Investigators and Coordinators). Angiotensin-neprilysin inhibition and clinical progression in surviving patients with heart failure. Circulation 2015; 131(1): 54–61.