Canadian Journal of Cardiology

Baseline Functional Class and Therapeutic Efficacy of Common Heart Failure Interventions: A Systematic Review and Meta-analysis

Published:January 07, 2015DOI:https://doi.org/10.1016/j.cjca.2014.12.031

      Abstract

      Background

      New York Heart Association (NYHA) functional class provides important prognostic information and is often used to select patients for cardiovascular therapies, yet, the effect of NYHA class on therapeutic efficacy has not been systematically studied.

      Methods

      In this systematic review and meta-analysis we compared the relative and absolute mortality benefit of 5 common heart failure interventions (angiotensin-converting enzyme [ACE] inhibitors, β-blockers, mineralocorticoid receptor antagonists [MRAs], implantable cardioverter defibrillator [ICD], and cardiac resynchronization therapy [CRT]) across NYHA class. We included 26 randomized clinical trials of these interventions that reported all-cause mortality stratified according to baseline NYHA class in 36,406 patients.

      Results

      Pooled relative risk for NYHA I/II vs III/IV strata were similar for ACE inhibitors (0.90 vs 0.88), β-blockers (0.72 vs 0.79), MRA (0.79 vs 0.75), and CRT (0.80 vs 0.80), with all heterogeneity P > 0.8. Conversely, ICD efficacy was greater for class I/II (relative risk, 0.65 vs 0.86, heterogeneity P = 0.02). The pooled absolute risk difference was smaller for NYHA I/II vs III/IV with ACE inhibitors (−0.02 vs −0.06, P = 0.12), β-blockers (−0.02 vs −0.05, P = 0.047), MRA (−0.03 vs −0.11, P = 0.001), and CRT (−0.01 vs −0.04, P = 0.036), but was similar across NYHA class for the ICD (−0.07 vs −0.05; P = 0.27).

      Conclusions

      Relative mortality reductions with most interventions were independent of baseline NYHA class. However, ICD efficacy was greater with NYHA I/II vs III/IV limitation, and absolute benefit was greater with higher NYHA class. For interventions other than the ICD, there is little evidence supporting use of NYHA class as a rigid criterion for selecting heart failure therapies.

      Résumé

      Introduction

      La classification fonctionnelle de la New York Heart Association (NYHA) fournit des informations importantes pour évaluer le pronostic et est souvent utilisée pour sélectionner les patients en vue de traitements cardiovasculaires. Cependant, les répercussions de la classification de la NYHA sur l’efficacité thérapeutique n’ont pas fait l’objet d’études systématiques.

      Méthodes

      Au cours de la revue systématique et de la méta-analyse, nous avons comparé les avantages sur la mortalité relative et absolue de 5 interventions habituelles pour le traitement de l’insuffisance cardiaque (inhibiteurs de l’enzyme de conversion de l’angiotensine [ECA], β-bloqueurs, antagonistes du récepteur minéralocorticoïde [ARM], défibrillateur cardioverteur implantable [DCI] et thérapie de resynchronisation cardiaque [TRC]) de toutes les classes de la NYHA. Nous avons inclus 26 essais cliniques aléatoires concernant ces interventions qui rapportaient la mortalité toutes causes confondues stratifiée selon la classification initiale de la NYHA de 36 406 patients.

      Résultats

      Le risque relatif global de la strate I/II de la NYHA vs la strate III/IV était similaire pour les inhibiteurs de l’ECA (0,90 vs 0,88), β-bloqueurs (0,72 vs 0,79), ARM (0,79 vs 0,75) et TRC (0,80 vs 0,80), toute hétérogénéité P > 0,8. En contrepartie, l’efficacité du DCI était plus grande pour la classe I/II (risque relatif, 0,65 vs 0,86, hétérogénéité P = 0,02). La différence du risque absolu global était plus petite pour la classe I/II de la NYHA vs la classe III/IV avec les inhibiteurs de l'ECA (−0,02 vs −0,06, P = 0,12), les β-bloqueurs (−0,02 vs −0,05, P = 0,047), les ARM (−0,03 vs −0,11, P = 0,001) et la TRC (−0,01 vs −0,04, P = 0,036), mais était similaire dans toutes les classes de la NYHA avec le DCI (−0,07 vs −0,05; P = 0,27).

      Conclusions

      Les réductions relatives de la mortalité liée à la plupart des interventions étaient indépendantes de la classification initiale de la NYHA. Cependant, le DCI a montré une plus grande efficacité à la classe I/II de la NYHA vs la classe III/IV, et un avantage absolu plus grand avec les classes supérieures de la NYHA. En ce qui concerne les interventions autres que le DCI, peu de données probantes soutenant l’utilisation de la classification NYHA comme critère de sélection rigoureux des traitements de l’insuffisance cardiaque existent.
      To read this article in full you will need to make a payment

      References

        • New York Heart Association Criteria Committee
        Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels.
        9th Ed. Little, Brown, Boston1994
        • Muntwyler J.
        • Abetel G.
        • Gruner C.
        • Follath F.
        One-year mortality among unselected outpatients with heart failure.
        Eur Heart J. 2002; 23: 1861-1866
        • Rostagno C.
        • Galanti G.
        • Comeglio M.
        • et al.
        Comparison of different methods of functional evaluation in patients with chronic heart failure.
        Eur J Heart Fail. 2000; 2: 273-280
        • Bennett J.A.
        • Riegel B.
        • Bittner V.
        • Nichols J.
        Validity and reliability of the NYHA classes for measuring research outcomes in patients with cardiac disease.
        Heart Lung. 2002; 31: 262-270
        • Goldman L.
        • Hashimoto B.
        • Cook E.F.
        • Loscalzo A.
        Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale.
        Circulation. 1981; 64: 1227-1234
        • Phelan D.
        • Thavendiranathan P.
        • Collier P.
        • Marwick T.H.
        Aldosterone antagonists improve ejection fraction and functional capacity independently of functional class: a meta-analysis of randomised controlled trials.
        Heart. 2012; 98: 1693-1700
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
        PLoS Med. 2009; 6: e1000097
      1. Food and Drug Administration Center for Drug Evaluation and Research. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed April 12, 2014.

        • Higgins J.P.
        • Altman D.G.
        • Gøtzsche P.C.
        • et al.
        The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • The CONSENSUS Trial Study Group
        Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival study.
        N Engl J Med. 1987; 316: 1429-1435
        • The SOLVD Investigators
        Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.
        N Engl J Med. 1991; 325: 293-302
        • Yusuf S.
        • Nicklas J.M.
        • Timmis G.
        • et al.
        Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.
        N Engl J Med. 1992; 327: 685-691
        • Keren G.
        • Pardes A.
        • Eschar Y.
        • et al.
        One-year clinical and echocardiographic follow-up of patients with congestive cardiomyopathy treated with captopril compared to placebo.
        Isr J Med Sci. 1994; 30: 90-98
      2. A randomized trial of beta-blockade in heart failure: the Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees.
        Circulation. 1994; 90: 1765-1773
      3. Effects of carvedilol, a vasodilator-beta-blocker, in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.
        Circulation. 1995; 92: 212-218
      4. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial.
        Lancet. 1999; 353: 9-13
      5. Effect of metoprolol cr/xl in chronic heart failure: Metoprolol cr/xl randomised intervention trial in congestive heart failure (MERIT-HF).
        Lancet. 1999; 353: 2001-2007
        • Beta-Blocker Evaluation of Survival Trial Investigators
        A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure.
        N Engl J Med. 2001; 344: 1659-1667
        • Packer M.
        • Coats A.J.
        • Fowler M.B.
        • et al.
        Effect of carvedilol on survival in severe chronic heart failure.
        N Engl J Med. 2001; 344: 1651-1658
        • Pitt B.
        • Zannad F.
        • Remme W.J.
        • et al.
        The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.
        N Engl J Med. 1999; 341: 709-717
        • Boccanelli A.
        • Mureddu G.F.
        • Cacciatore G.
        • et al.
        Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF Study): final results.
        Eur J Heart Fail. 2009; 11: 68-76
        • Zannad F.
        • McMurray J.J.
        • Krum H.
        • et al.
        Eplerenone in patients with systolic heart failure and mild symptoms.
        N Engl J Med. 2011; 364: 11-21
        • Moss A.J.
        • Hall W.J.
        • Cannom D.S.
        • et al.
        Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia.
        N Engl J Med. 1996; 335: 1933-1940
        • Moss A.J.
        • Zareba W.
        • Hall W.J.
        • et al.
        Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.
        N Engl J Med. 2002; 346: 877-883
        • Bristow M.R.
        • Saxon L.A.
        • Boehmer J.
        • et al.
        Cardiac resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.
        N Engl J Med. 2004; 350: 2140-2150
        • Kadish A.
        • Dyer A.
        • Daubert J.P.
        • et al.
        Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.
        N Engl J Med. 2004; 350: 2151-2158
        • Bardy G.H.
        • Lee K.L.
        • Mark D.B.
        • et al.
        Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.
        N Engl J Med. 2005; 352: 225-237
        • Abraham W.T.
        • Fisher W.G.
        • Smith A.L.
        • et al.
        Cardiac resynchronization in chronic heart failure.
        N Engl J Med. 2002; 346: 1845-1853
        • Young J.B.
        • Abraham W.T.
        • Smith A.L.
        • et al.
        Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD trial.
        JAMA. 2003; 289: 2685-2694
        • Abraham W.T.
        • Young J.B.
        • Leon A.R.
        • et al.
        Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure.
        Circulation. 2004; 110: 2864-2868
        • Cleland J.G.
        • Daubert J.C.
        • Erdmann E.
        • et al.
        The effect of cardiac resynchronization on morbidity and mortality in heart failure.
        N Engl J Med. 2005; 352: 1539-1549
        • Linde C.
        • Abraham W.T.
        • Gold M.R.
        • et al.
        Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms.
        J Am Coll Cardiol. 2008; 52: 1834-1843
        • Moss A.J.
        • Hall W.J.
        • Cannom D.S.
        • et al.
        Cardiac-resynchronization therapy for the prevention of heart-failure events.
        N Engl J Med. 2009; 361: 1329-1338
        • Tang A.S.
        • Wells G.A.
        • Talajic M.
        • et al.
        Cardiac-resynchronization therapy for mild-to-moderate heart failure.
        N Engl J Med. 2010; 363: 2385-2395
        • Cohn J.N.
        • Tognoni G.
        • Valsartan Heart Failure Trial Investigators
        A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.
        N Engl J Med. 2001; 345: 1667-1675
        • Young J.B.
        • Dunlap M.E.
        • Pfeffer M.A.
        • et al.
        Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials.
        Circulation. 2004; 110: 2618-2626
        • Hamroff G.
        • Katz S.D.
        • Mancini D.
        • et al.
        Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure.
        Circulation. 1999; 99: 990-992
        • Haynes R.B.
        • Sackett D.L.
        • Guyatt G.H.
        • Tugwell P.
        Chapter 6: The principles behind the tactics of performing therapeutic trials.
        in: Clinical Epidemiology: How to Do Clinical Practice Research. Lippincott, Williams & Wilkins, 2006: 173-243
        • Ørn S.
        • Dickstein K.
        How do heart failure patients die?.
        Eur Heart J Suppl. 2002; 4: D59-D65
        • Liu P.
        • Arnold M.
        • Belenkie I.
        • et al.
        The 2001 Canadian Cardiovascular Society consensus guideline update for the management and prevention of heart failure.
        Can J Cardiol. 2001; 17: 5E-25E
        • McKelvie R.S.
        • Moe G.W.
        • Cheung A.
        • et al.
        The 2011 Canadian Cardiovascular Society heart failure management guidelines update: focus on sleep apnea, renal dysfunction, mechanical circulatory support, and palliative care.
        Can J Cardiol. 2011; 27: 319-338
        • Hernandez A.F.
        • Hammill B.G.
        • O'Connor C.M.
        • et al.
        Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry.
        J Am Coll Cardiol. 2009; 53: 184-192
        • Packer D.L.
        • Prutkin J.M.
        • Hellkamp A.S.
        • et al.
        Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the Sudden Cardiac Death in Heart Failure trial.
        Circulation. 2009; 120: 2170-2176
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure. A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
        • Covey J.
        A meta-analysis of the effects of presenting treatment benefits in different formats.
        Med Decis Making. 2007; 27: 638-654
        • Stacey D.
        • Bennett C.L.
        • Barry M.J.
        • et al.
        Decision aids for people facing health treatment or screening decisions.
        Cochrane Database Syst Rev. 2011; : CD001431
        • Rywik S.L.
        • Wagrowska H.
        • Broda G.
        • et al.
        Heart failure in patients seeking medical help at outpatients clinics. Part I. General characteristics.
        Eur J Heart Fail. 2000; 2: 413-421
        • Arnold J.M.
        • Ignaszewski A.
        • Kaan A.
        • et al.
        Cardiovascular co-morbidities and five year survival in a large contemporary outpatient cohort of patients with chronic heart failure.
        J Am Coll Cardiol. 2012; 59: E1051