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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

The current role of cardiac resynchronization therapy in reducing mortality and hospitalization in heart failure patients: a meta-analysis from clinical trials

A Rossi, G Rossi, M Piacenti, U Startari, L Panchetti, and MA Morales.

Review published: 2008.

CRD summary

This review concluded that cardiac resynchronisation therapy significantly reduced all-cause mortality and hospitalisations in patients with heart failure. The effect was non-significant in patients with implantable cardiac defibrillators. The authors' conclusions appear to be supported by the data presented but the absence of review methods and study quality assessment made it difficult to evaluate their reliability.

Authors' objectives

To assess the effects of atrial-synchronised biventricular pacing (cardiac resynchronisation therapy) in patients with heart failure on all-cause mortality and hospitalisation for worsening heart failure.


MEDLINE and the clinical trial database of the National Institutes of Health (ClinicalTrials.gov) were searched for articles published from 1994 up to October 2006. Search terms were reported. Abstracts presented during the scientific sessions of the American College of Cardiology (1994 to 2006), the American Heart Association (1994 to 2005) and the North American Society of Pacing and Electrophysiology (1994 to 2006) were also searched. There was no restriction according to language or publication status.

Study selection

Studies were eligible if they were randomised controlled trials (RCTs) on cardiac resynchronisation therapy for symptomatic congestive heart failure in patients with left ventricular dysfunction and sinus rhythm and reported on death and hospitalisation for heart failure. Trials had to have a follow-up of at least three months. Trials including implantation of cardioverter defibrillators (during biventricular stimulation) or enrolling patients with atrial arrhythmias were excluded.

The included trials studied patients with NYHA (New York Heart Association) class II-III-IV (class III or IV in 68% to 100% of patients), a wide QRS (158 to 174 ms, most patients with complete left bundle branch block), left ventricular ejection fraction of less than 30% and sinus rhythm. Mean patient age was between 64 and 67 years; 68% and 84% of study participants were men; 37% and 70% of patients had ischaemic cardiopathy. Baseline medication included angiotensin converter enzyme inhibitors or angiotensin II receptor blockers in 87% to 96% of patients and β-blockers in 28% to 72% of patients. Follow-up was between three and 50 months. Four trials included patients with pacemakers and two trials included patients with implantable cardiac defibrillators.

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Methods of synthesis

Data were analysed using hazard rations which were pooled using a fixed-effects model and 95% and 99% confidence intervals (CIs). Statistical heterogeneity was assessed using the χ2 test. When heterogeneity was present, random-effects models were also used (inverse variance method, DerSimonian and Laird). Effects of baseline characteristics on heterogeneity were evaluated in a meta-regression analysis (assessing the effects of mean age, sex, percentage of ischaemic patients, left ventricular ejection fraction, NYHA class III-IV, β-blocker treatment and implantable cardiac defibrillators treatment).

Results of the review

Six RCTs trials with a total of 3,108 participants were included. The authors did not discuss study quality although it was noted that longer follow-up periods would have been desirable.

Only one of the six trials included reported a significant reduction in all cause mortality. Overall, the meta-analysis showed that mortality was reduced significantly with cardiac resynchronisation therapy (hazard ratio 0.72, 95% CI: 0.60, 0.86). In patients without an implantable cardiac defibrillator device, mortality was significantly reduced, with a hazard ratio of 0.70 (95% CI: 0.58, 0.85). In patients with an implantable cardiac defibrillator device, there was a non-significant reduction in mortality with cardiac resynchronisation compared to implantable cardiac defibrillators only (hazard ratio 0.80, 95% CI: 0.48, 1.32).

Overall, cardiac resynchronisation therapy reduced hospitalisation for worsening heart failure significantly by 37% (hazard ratio 0.63, 95% CI: 0.44, 0.91, p=0.02). There was significant heterogeneity which disappeared when considering patients with or without implantable cardiac defibrillator devices separately. In patients without implantable cardiac defibrillator devices, hospitalisation was reduced by 53% (hazard ratio 0.47, 95% CI: 0.37, 0.61), whereas there was no significant reduction in hospitalisations comparing cardiac resynchronisation in implantable cardiac defibrillator patients versus implantable cardiac defibrillator only (hazard ratio 0.92, 95% CI: 0.68, 1.25).

In the meta-regression analysis, the main effect was seen for implantable cardiac defibrillator versus no implantable cardiac defibrillator treatment; implantable cardiac defibrillator studies also had a higher percentage of ischaemic patients (69% versus 43%, p=0.000). The meta-regression analysis suggested that benefits of cardiac resynchronisation therapy decreased with an increase of the proportion of ischaemic patients (p=0.001). The highest hospitalisation rate was seen in patients without cardiac resynchronisation and without implantable cardiac defibrillator (26.7%). The rates in the other groups (implantable cardiac defibrillator only, implantable cardiac defibrillator plus cardiac resynchronisation, cardiac resynchronisation only) were similar. The meta-regression analysis showed no effect of β-blocker therapy.

Authors' conclusions

Cardiac resynchronisation therapy reduced all-cause mortality by 28% and new hospitalisations for worsening heart failure by 37%. Patients with implantable cardiac defibrillators alone and implantable cardiac defibrillators plus cardiac resynchronisation had a significant reduction in hospitalisation rate for worsening heart failure compared to patients without implantable cardiac defibrillators or cardiac resynchronisation. Among patients with implantable cardiac defibrillators, cardiac resynchronisation showed only a slight impact on all-cause mortality reduction and no clear impact on hospitalisations for worsening heart failure (but these patients also had a higher rate of cardiac ischaemia).

CRD commentary

This systematic review addressed a clearly stated research question with appropriate definition of inclusion criteria. The literature search included a limited number of relevant databases and additional searches. Search terms were listed. However, further review methodology was not described and quality assessment of the included studies was not mentioned. Study flow was described and sufficient details of the included trials were given. The authors' conclusions appeared to follow from the data presented, but the absence of reporting of review methods and quality assessment made it difficult to evaluate their reliability. In addition, the "slight reduction in mortality" after cardiac resynchronisation reported for patients with implantable cardiac defibrillator devices was non-significant.

Implications of the review for practice and research

Practice: The authors made no specific recommendations for practice.

Research: The authors stated that more randomised trials with longer follow-ups are needed and that trials should report the specific cause of death when reporting on mortality.


Not stated.

Bibliographic details

Rossi A, Rossi G, Piacenti M, Startari U, Panchetti L, Morales M A. The current role of cardiac resynchronization therapy in reducing mortality and hospitalization in heart failure patients: a meta-analysis from clinical trials. Heart and Vessels 2008; 23(4): 217-223. [PubMed: 18649051]

Indexing Status

Subject indexing assigned by NLM


Cardiac Pacing, Artificial /mortality; Defibrillators, Implantable /statistics & numerical data; Disease Progression; Heart Failure /mortality /physiopathology /therapy; Hospitalization /statistics & numerical data; Humans; Pacemaker, Artificial /statistics & numerical data; Randomized Controlled Trials as Topic /statistics & numerical data; Risk Assessment; Time Factors; Treatment Outcome



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 18649051

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