Heart failure Complex clinical syndrome caused by any structural or - - PowerPoint PPT Presentation

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

Among patients with causes of heart failure, how effective are in reducing and ? non-ischemic

beta-blockers all cause mortality 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 through database searching: 94 Relevant records identified through other sources: 20 Records after duplicates removed: 106

Records screened: 106 Studies included in the meta-analysis: 5

Full-text articles excluded based on: no results reported on non-ischemic sub-group: 13

Full-text articles assessed for eligibility: 18 Identification Screening Eligibility Included

Potentially relevant records identified through database searching: 94 Relevant records identified through other sources: 20 Records after duplicates removed: 106

Records screened: 106 Studies included in the meta-analysis: 5

Full-text articles excluded based on: no results reported on non-ischemic sub-group: 13

Full-text articles assessed for eligibility: 18 Identification Screening Eligibility Included

Potentially relevant records identified through database searching: 94 Relevant records identified through other sources: 20 Records after duplicates removed: 106

Records screened: 106 Studies included in the meta-analysis: 5

Full-text articles excluded based on: no results reported on non-ischemic sub-group: 13

Full-text articles assessed for eligibility: 18 Identification Screening Eligibility Included

Sele lection

• n C

Cri riteri ria

 Inclusion Criteria

 randomized trials  comparing beta

blockers with placebo

 patients with heart

failure with non- ischemic etiology

 ejection fraction ≤ 40%  reported on mortality

and/or hospitalizations for worsening heart failure

 Exclusion Criteria

 non-randomized  compared beta blockers

with other betablockers

• r other heart failure

treatment

 did not specify results of

mortality and hospitalizations for the non-ischemic subgroup

Potentially relevant records identified through database searching: 94 Relevant records identified through other sources: 20 Records after duplicates removed: 106

Records screened: 106 Studies included in the meta-analysis: 5

Full-text articles excluded based on: no results reported on non-ischemic sub-group: 13

Full-text articles assessed for eligibility: 18 Identification Screening Eligibility Included

Potentially relevant records identified through database searching: 94 Relevant records identified through other sources: 20 Records after duplicates removed: 106

Records screened: 106 Studies included in the meta-analysis: 5

Full-text articles excluded based on: no results reported on non-ischemic sub-group: 13

Full-text articles assessed for eligibility: 18 Identification Screening Eligibility Included

Study Participants Intervention Outcome Method Bias Patients Overall # Non- ischemic treatment mean ffup CIBIS I Age 18- 75 yrs, with chronic heart failure NYHA III or IV. On diuretic and vasodilator therapy w/ EF≤40% 641 (321 placebo 320 bisoprolol) 350 (115 placebo 117 bisoprolol) Bisoprolol vs placebo 1.9 yrs Mortality, Bisoprolol tolerability RCT, double blind A CIBIS II Age 18- 80 yrs, with chronic heart failure NYHA III or IV. On diuretic and ACEi therapy w/ EF≤40% 2647 (1320 placebo 1327 bisoprolol) 317 (157 placebo 160 bisoprolol) Bisoprolol vs placebo 1.3 yrs Mortality, hospitalizati

• n

Cardiac Death Cardiac hospitalizati

• n

RCT, double blind A MDC Age 16- 75 years, with idiopathic dilated cardiomyopathy w/ EF≤40% 383 (194 placebo 189 metoprolol) Metoprolol vs placebo 1.5 yrs Mortality and need for transplantat RCT, double blind A Merit-HF Age 40-80 yrs , with chronic heart failure NYHA II or IV. On optimal treatment w/ EF≤40% 3991 (2001 placebo 1990 metoprolo l) 1397 (701 placebo 696 metoprolol) Metoprolol vs placebo 1 yr Mortality, hospitalizati

• n

RCT, double blind A US Carvedilol Symptomatic heart failure w/ EF≤35% 1094 (398 placebo 696 bisoprolol ) 350 (115 placebo 117 bisoprolol) Carvedilol vs placebo 6-12 mos Mortality, safety RCT, double blind A BIAS

A A A A A

Data Collection and Analysis

 Data on as well as

were extracted from each trial using a standardized data collection form

 Analysis was done using  Heterogeneity was tested using

as well as



and considered to have significant heterogenity

Cochrane Review Manager software version 5.2 total mortality hospitalizations chi-square test I2 statistics

p value < 0.1 I2 value of ≥ 50%

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

 The results of this analysis:

 Beta blockers reduce mortality and

hospitalizations in non-ischemic heart failure patients

 Risk reduction of

for mortality, comparable to 34% risk reduction for mortality of the entire cohort.

Discussion

28%

Discussion

 Possible mechanisms:

 Restoration of the low and high frequency

• scillation 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