Background Effects of beta-blockers on the prognosis of the heart failure patients with preserved ejection fraction (HFpEF) remain controversial. The aim of this meta-analysis was to determine the impact of beta-blockers on mortality and hospitalization in the patients with HFpEF. Methods A search of MEDLINE, EMBASE, and the Cochrane Library databases from 2005 to June 2013 was conducted. Clinical studies reporting outcomes of mortality and/or hospitalization for patients with HFpEF (EF ≥ 40%), being assigned to beta-blockers treatment and non-beta-blockers control group were included. Results A total of 12 clinical studies (2 randomized controlled trials and 10 observational studies) involving 21,206 HFpEF patients were included for this meta-analysis. The pooled analysis demonstrated that beta-blocker exposure was associated with a 9% reduction in relative risk for all-cause mortality in patients with HFpEF (95% CI: 0.87 – 0.95; P < 0.001). Whereas, the all-cause hospitalization, HF hospitalization and composite outcomes (mortality and hospitalization) were not affected by this treatment (P = 0.26, P = 0.97, and P = 0.88 respectively). Conclusions The beta-blockers treatment for the patients with HFpEF was associated with a lower risk of all-cause mortality, but not with a lower risk of hospitalization. These finding were mainly obtained from observational studies, and further investigations are needed to make an assertion.
References
[1]
Lam CS, Donal E, Kraigher-Krainer E, Vasan RS (2011) Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail 13: 18–28. doi: 10.1093/eurjhf/hfq121
[2]
Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, et al. (2003) Gender, age, and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 41: 217–223. doi: 10.1016/s0735-1097(02)02696-7
[3]
Smith GL, Masoudi FA, Vaccarino V, Radford MJ, Krumholz HM (2003) Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. J Am Coll Cardiol 41: 1510–1518. doi: 10.1016/s1062-1458(03)00300-3
[4]
Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, et al. (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344: 1651–1658. doi: 10.1056/nejm200105313442201
[5]
Krum H, Roecker EB, Mohacsi P, Rouleau JL, Tendera M, et al. (2003) Effects of initiating carvedilol in patients with severe chronic heart failure: results from the COPERNICUS Study. JAMA 289: 712–718. doi: 10.1001/jama.289.6.712
[6]
Paulus WJ, van Ballegoij JJ (2010) Treatment of heart failure with normal ejection fraction: an inconvenient truth!. J Am Coll Cardiol 55: 526–537. doi: 10.1016/j.jacc.2009.06.067
[7]
Dobre D, van Veldhuisen DJ, DeJongste MJ, Lucas C, Cleuren G, et al. (2007) Prescription of beta-blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival. Eur J Heart Fail 9: 280–286. doi: 10.1016/j.ejheart.2006.07.008
[8]
Shah R, Wang Y, Foody JM (2008) Effect of statins, angiotensin-converting enzyme inhibitors, and beta blockers on survival in patients >or = 65 years of age with heart failure and preserved left ventricular systolic function. Am J Cardiol 101: 217–222. doi: 10.1016/j.amjcard.2007.08.050
[9]
El-Refai M, Peterson EL, Wells K, Swadia T, Sabbah HN, et al. (2013) Comparison of Beta-blocker effectiveness in heart failure patients with preserved ejection fraction versus those with reduced ejection fraction. J Card Fail 19: 73–79. doi: 10.1016/j.cardfail.2012.11.011
[10]
van Veldhuisen DJ, Cohen-Solal A, Bohm M, Anker SD, Babalis D, et al. (2009) Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: Data From SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol 53: 2150–2158. doi: 10.1016/j.jacc.2009.02.046
[11]
Yamamoto K, Origasa H, Hori M (2013) Effects of carvedilol on heart failure with preserved ejection fraction: the Japanese Diastolic Heart Failure Study ( J-DHF ). Eur J Heart Fail 15: 110–118. doi: 10.1093/eurjhf/hfs141
[12]
Farasat SM, Bolger DT, Shetty V, Menachery EP, Gerstenblith G, et al. (2010) Effect of Beta-blocker therapy on rehospitalization rates in women versus men with heart failure and preserved ejection fraction. Am J Cardiol 105: 229–234. doi: 10.1016/j.amjcard.2009.09.008
[13]
Holland DJ, Kumbhani DJ, Ahmed SH, Marwick TH (2011) Effects of treatment on exercise tolerance, cardiac function, and mortality in heart failure with preserved ejection fraction. A meta-analysis. J Am Coll Cardiol 57: 1676–1686. doi: 10.1016/j.jacc.2010.10.057
[14]
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151: 264–269, W64.
[15]
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, et al. (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283: 2008–2012. doi: 10.1001/jama.283.15.2008
[16]
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, et al. (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17: 1–12. doi: 10.1016/0197-2456(95)00134-4
[17]
Spruance SL, Reid JE, Grace M, Samore M (2004) Hazard ratio in clinical trials. Antimicrob Agents Chemother 48: 2787–2792. doi: 10.1128/aac.48.8.2787-2792.2004
[18]
Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J (2007) Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 298: 2654–2664. doi: 10.1001/jama.298.22.2654
[19]
Pan A, Sun Q, Okereke OI, Rexrode KM, Hu FB (2011) Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review. JAMA 306: 1241–1249. doi: 10.1001/jama.2011.1282
[20]
Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21: 1539–1558. doi: 10.1002/sim.1186
[21]
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188. doi: 10.1016/0197-2456(86)90046-2
[22]
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50: 1088–1101. doi: 10.2307/2533446
[23]
Fukuta H, Sane DC, Brucks S, Little WC (2005) Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 112: 357–363. doi: 10.1161/circulationaha.104.519876
[24]
Chan JD, Rea TD, Smith NL, Siscovick D, Heckbert SR, et al. (2005) Association of beta-blocker use with mortality among patients with congestive heart failure in the Cardiovascular Health Study (CHS). Am Heart J 150: 464–470. doi: 10.1016/j.ahj.2004.12.022
[25]
Grigorian SL, Roman AV, Ramos PM, Veloso PR, Bandin DM, et al. (2006) Angiotensin-converting enzyme inhibitors prescription is associated with longer survival among patients hospitalized for congestive heart failure who have preserved systolic function: a long-term follow-up study. J Card Fail 12: 128–133. doi: 10.1016/j.cardfail.2005.09.001
[26]
Hernandez AF, Hammill BG, O'Connor CM, Schulman KA, Curtis LH, et al. (2009) 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 53: 184–192.
[27]
Tehrani F, Phan A, Chien CV, Morrissey RP, Rafique AM, et al. (2009) Value of medical therapy in patients >80 years of age with heart failure and preserved ejection fraction. Am J Cardiol 103: 829–833. doi: 10.1016/j.amjcard.2008.11.047
[28]
Nevzorov R, Porath A, Henkin Y, Kobal SL, Jotkowitz A, et al. (2012) Effect of beta blocker therapy on survival of patients with heart failure and preserved systolic function following hospitalization with acute decompensated heart failure. European Journal of Internal Medicine 23: 374–378. doi: 10.1016/j.ejim.2012.01.011
[29]
Carson P, Johnson G, Fletcher R, Cohn J (1996) Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT). J Am Coll Cardiol 27: 642–649. doi: 10.1016/0735-1097(95)00503-x
[30]
Ghio S, Magrini G, Serio A, Klersy C, Fucili A, et al. (2006) Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy. Eur Heart J 27: 562–568. doi: 10.1093/eurheartj/ehi735
[31]
Fonarow GC, Stough WG, Abraham WT, Albert NM, Gheorghiade M, et al. (2007) Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry. J Am Coll Cardiol 50: 768–777. doi: 10.1016/j.jacc.2007.04.064
[32]
Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, et al.. (2013) 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.
[33]
Nohria A, Tsang SW, Fang JC, Lewis EF, Jarcho JA, et al. (2003) Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J Am Coll Cardiol 41: 1797–1804. doi: 10.1016/s0735-1097(03)00309-7
[34]
Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, et al. (2012) Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol 59: 998–1005. doi: 10.1016/j.jacc.2011.11.040
[35]
Zhou J, Shi H, Zhang J, Lu Y, Fu M, et al. (2010) Rationale and design of the beta-blocker in heart failure with normal left ventricular ejection fraction (beta-PRESERVE) study. Eur J Heart Fail 12: 181–185. doi: 10.1093/eurjhf/hfp193
