Effect of spironolactone in patients with heart failure and preserved left ventricular function – TOPCAT study

Czech version

Authors: Jiří Widimský Sr
Authors‘ workplace: Klinika kardiologie IKEM Praha, přednosta prof. MUDr. Josef Kautzner, CSc.
Published in: Vnitř Lék 2015; 61(5): 376-380
Category: 90th birthday of prof. MD. Jiri Widimsky, MD., FESC, FAHA

Overview

The TOPCAT study followed the effect of spironolactone on a chronic heart failure with a preserved left ventricular ejection fraction. The study did not find any impact on the primary goal of the study, i.e. a combination of cardiovascular mortality, managed cardiac arrest or hospitalization rate for heart failure treatment. The only finding of the study was the decrease in hospitalization rates for a heart failure. A post hoc analysis, however, identified a significant difference between patients from the Americas (USA, Canada, Argentina, Brazil) on the one hand and those from Russia/Georgia on the other. The differences were rather striking. Whereas the former manifested a significant reduction in the incidence of the primary goal, i.e. cardiovascular mortality and hospitalization with heart failure through treatment with spironolactone, the incidence of all clinical events was considerably lower in Russia/Georgia and no impact of spironolactone at all on any of the goals was identified regarding the patients from Russia/Georgia. This post hoc analysis therefore suggested a possible therapeutic effect of spironolactone in the Americas, as well as in the populations of similar characteristics. Most studies accept a definition only based on the heart failure with a preserved left ventricular ejection fraction. The study points to the need to further elaborate this definition which also has to consider changes of the left ventricular diastolic function when defining a diastolic heart failure.

Key words:
diastolic heart failure – spironolactone – TOPCAT study

Sources

1. Yusuf S, Pfeffer MA, Swedberg K et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 2003; 362(9386): 777–781.

2. Massie BM, Carson PE, McMurray JJ et al. I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008; 359(23): 2456–2467.

3. Ahmed A, Rich MW, Fleg JL et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the Ancillary Digitalis Investigation Group trial. Circulation 2006; 114(5): 397–403.

4. Caruana L, Petrie M, Davie AP, McMurray JJ. Do patients with suspected heart failure and preserved left ventricular systolic function suffer from “diastolic heart failure” or from misdiagnosis? A prospective descriptive study. Br Med J 2000; 321(7255): 215–218.

5. Cleland JG, Tendera H, Adamus J et al. PEP-CHF Investigators. The perindopril in elderly people of chronic heart failure (PEP-CHF) study. Eur Heart J 2006; 27(19): 2338–2345.

6. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341(10): 709–717.

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

8. Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348(14): 1309–1321.

9. Pitt B, Pfeffer MA, Assmann SF et al. TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 2014; 370(15): 1383–1392.

10. Pfeffer MA, Clagett B, Assmann SF et al. Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. Circulation 2015; 131(1): 34–42.

11. Rossignol P, Zannad F. Regional Differences in Heart Failure With Preserved Ejection Fraction Trials. When Nephrology Meets Cardiology but East Does Not Meet West. Circulation 2015; 131(1): 7–10.

12. Kristensen S, Køber L, Jhund PS et al. International Geographic Variation in Event Rates in Trials of Heart Failure With Preserved and Reduced Ejection Fraction. Circulation 2015; 131(1): 43–53.