Heart failure Complex clinical syndrome caused by any structural or functional impairment of ventricular filling or ejection of blood Estimated prevalence of ~2.4% (NHANES)
Etiology Generally divided into two major categories: Ischemic causes non ischemic causes Coronary artery disease still remains as the leading cause of heart failure, accounting for more than 50% of the heart failure cases in the Framingham study
Survival Survival is grim 5 year survival rate = 59%
Current Treatment Current recommendations B blockers on top of an ACEi or ARB for the treatment of heart failure Trials that support treatment include a majority of ischemic heart failure patients
Evidence Lacking the trials that enroll mostly non-ischemic heart failure patients are small and underpowered to analyze mortality endpoints
Research Quest uestion non-ischemic Among patients with causes of beta-blockers heart failure, how effective are all cause mortality in reducing and hospitalization for worsening heart failure ?
Object jective To determine the effectiveness of beta- blockers in heart failure patients with non-ischemic etiologies in decreasing: All cause mortality Hospitalization for worsening heart failure
METH THODOLOGY
Search Database: PUBMED MEDLINE Cochrane Controlled Trial Register Search Terms: “Beta blockers, heart failure, mortality, hospitalization, RCT and placebo.” Other sources Review of all trials included in a recent Meta- analysis on beta blockers
Potentially relevant records identified Relevant records identified through database searching: 94 through other sources: 20 Identification Records after duplicates removed: 106 Screening Records screened: 106 Eligibility Full-text articles excluded Full-text articles assessed based on: no results for eligibility: 18 reported on non-ischemic sub-group: 13 Included Studies included in the meta-analysis: 5
Potentially relevant records identified Relevant records identified through database searching: 94 through other sources: 20 Identification Records after duplicates removed: 106 Screening Records screened: 106 Eligibility Full-text articles excluded Full-text articles assessed based on: no results for eligibility: 18 reported on non-ischemic sub-group: 13 Included Studies included in the meta-analysis: 5
Potentially relevant records identified Relevant records identified through database searching: 94 through other sources: 20 Identification Records after duplicates removed: 106 Screening Records screened: 106 Eligibility Full-text articles excluded Full-text articles assessed based on: no results for eligibility: 18 reported on non-ischemic sub-group: 13 Included Studies included in the meta-analysis: 5
Sele lection on C Cri riteri ria Inclusion Criteria Exclusion Criteria randomized trials non-randomized comparing beta compared beta blockers blockers with placebo with other betablockers or other heart failure patients with heart treatment failure with non- ischemic etiology did not specify results of mortality and ejection fraction ≤ 40% hospitalizations for the reported on mortality non-ischemic subgroup and/or hospitalizations for worsening heart failure
Potentially relevant records identified Relevant records identified through database searching: 94 through other sources: 20 Identification Records after duplicates removed: 106 Screening Records screened: 106 Eligibility Full-text articles excluded Full-text articles assessed based on: no results for eligibility: 18 reported on non-ischemic sub-group: 13 Included Studies included in the meta-analysis: 5
Potentially relevant records identified Relevant records identified through database searching: 94 through other sources: 20 Identification Records after duplicates removed: 106 Screening Records screened: 106 Eligibility Full-text articles excluded Full-text articles assessed based on: no results for eligibility: 18 reported on non-ischemic sub-group: 13 Included Studies included in the meta-analysis: 5
Participants Intervention Study Outcome Method Bias BIAS Non- mean Patients Overall # treatment ischemic ffup CIBIS I Age 18- 75 yrs, with 641 350 Bisoprolol 1.9 Mortality, RCT, A chronic heart failure (321 (115 vs placebo yrs Bisoprolol double A NYHA III or IV. On diuretic placebo placebo 117 tolerability blind and vasodilator therapy 320 bisoprolol) w/ EF ≤ 40% bisoprolol) CIBIS II Age 18- 80 yrs, with 2647 317 Bisoprolol 1.3 Mortality, RCT, A A chronic heart failure (1320 (157 vs placebo yrs hospitalizati double NYHA III or IV. On diuretic placebo placebo 160 on Cardiac blind and ACEi therapy w/ 1327 bisoprolol) Death EF ≤ 40% bisoprolol) Cardiac hospitalizati on MDC Age 16- 75 years, with 383 Metoprolol 1.5 Mortality and RCT, A idiopathic dilated (194 placebo vs placebo yrs need for double A cardiomyopathy w/ 189 metoprolol) transplantat blind EF ≤ 40% Merit-HF Age 40-80 yrs , with 3991 1397 Metoprolol 1 yr Mortality, RCT, A A chronic heart failure (2001 (701 vs placebo hospitalizati double NYHA II or IV. On optimal placebo placebo on blind treatment w/ EF ≤ 40% 1990 696 metoprolo metoprolol) l) US Symptomatic heart 1094 350 Carvedilol 6-12 Mortality, RCT, A A failure w/ EF ≤ 35% Carvedilol (398 (115 vs placebo mos safety double placebo placebo blind 696 117 bisoprolol bisoprolol) )
Data Collection and Analysis Data on as well as total mortality were extracted from hospitalizations each trial using a standardized data collection form Analysis was done using Cochrane Review Manager software version 5.2 Heterogeneity was tested using I 2 statistics as well as chi-square test I 2 value of ≥ 50% and p value < 0.1 considered to have significant heterogenity
Total Mortality
Hospitalizations
Discussion Treatment with beta-blockers shows improved outcomes Consistent results in multiple trials Independent of the type of beta blocker Chatterjee, S., Biondi-Zoccai, G., Abbate , A., et al. Benefits Of Β Blockers In Patients With Heart Failure And Reduced Ejection Fraction: Network Meta-Analysis. BMJ 2013;346:f55
Discussion The results of this analysis: Beta blockers reduce mortality and hospitalizations in non-ischemic heart failure patients Risk reduction of 28% for mortality, comparable to 34% risk reduction for mortality of the entire cohort.
Discussion Possible mechanisms: Restoration of the low and high frequency oscillation of the muscle sympathetic nerve activity variability Restoration of baroreceptor tone and increasing vagal tone ○ Both contributes to decreasing sudden death and disease progression Kubo, T, Azevedo, E.R., Newton, G.E., et al. Beta-Blockade Restores Muscle Sympathetic Rhythmicity in Human Heart Failure. Circulation Journal 2011. Vol.75, 1400-1408 Sanderson, J. E. , Yeung, L.Y., Chan, S., et al. Effect of β -blockade on Baroreceptor and Autonomic Function in Heart Failure.Clinical Science (1999) 96, 137–146
LIMIT ITATIO ION This meta-analysis was limited to the data reported by the included studies. Unpublished studies and those whose access is restricted, may not have been included.
CONCLUSION The mortality benefit and decrease in hospitalization seen with the addition of beta-blockers to maximal medical therapy among patients is not limited to ischemic causes alone.
RECOMMENDATION Patients with non ischemic heart failure should be started on beta blockers in the absence of contraindications
Recommend
More recommend
