Effects of statin treatment on cardiac function in patients with chronic heart failure: a meta-analysis of randomized controlled trials

CRD summary

This review concluded that statin treatment might time-dependently increase left ventricular ejection fraction and may reduce left ventricular end-diastolic diameter, left-ventricular end-systolic diameter, B-type natriuretic peptide and New York Heart Association functional class in patients with chronic heart failure. Given the low quality of included studies and the presence of statistical heterogeneity, the authors' conclusions should be treated with caution.

Authors' objectives

To assess the impact of statin treatment on cardiac function in patients with chronic heart failure.

Searching

PubMed, EMBASE and EBM Reviews were searched to July 2009 for articles in any language and of any publication status. Search terms were reported. Reference lists of included studies were searched.

Study selection

Prospective randomised controlled trials (RCTs) that evaluated statin treatment compared to non-statin treatment or placebo in addition to concurrent therapy in patients with chronic heart failure were eligible for inclusion. Eligible outcomes were: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left-ventricular end-systolic diameter (LVESD), B-type natriuretic peptide and New York Heart Association functional class.

Most of the included studies evaluated atorvastatin. Doses ranged from 10mg/day to 80mg/day. Other treatments investigated were rosuvastatin, cerivastatin and simvastatin. The proportion of males ranged from 54% to 81%. Mean age ranged from 38 to 69 years. Most studies did not include participants with ischaemic aetiology. Patients from all New York Heart Association functional classes (I-IV) were included. Most patients had normal low-density lipoprotein (LDL) levels. Follow-up ranged from one month to 31 months.

Two reviewers independently selected the studies. Disagreements were resolved by consensus.

Assessment of study quality

Study quality was assessed using the Jadad scale of randomisation, blinding and withdrawals/dropouts to allocate scores up to a maximum of 5.

It appeared that quality assessment was carried out independently by two reviewers.

Data extraction

Data were extracted to enable calculation of mean change from baseline to follow-up for all outcomes. Two reviewers independently extracted data.

Methods of synthesis

Pooled weighted mean differences (WMD) were calculated with 95% confidence intervals (CI) using random-effects models. Statistical heterogeneity was assessed using the I² statistic. Meta-regression was conducted to investigate heterogeneity using year of publication, sex of patient, chronic heart failure aetiology, baseline LVEF and follow-up as factors. Sensitivity analyses excluded each study in turn. Publication bias was assessed using the Begg adjusted-rank correlation test and Egger regression asymmetry test.

Results of the review

Eleven RCTs (n=590 participants) were included for review. Study size ranged from 15 to 108 participants. Study quality was low to moderate: one study scored 1 on the Jadad scale, three scored 2, five scored 3, one scored 4 and one scored 5.

Statin treatment significantly improved left ventricular ejection fraction compared to standard medical treatment (WMD 3.35%, 95% CI 0.80 to 5.91, I²=99.6%; 10 studies, n=575). Significant benefits were observed on left ventricular end-diastolic diameter (WMD -3.77mm, 95% CI -6.24 to -1.31, I²=99.0%; four studies, n=306), left ventricular end systolic diameter (WMD -3.57mm, 95% CI -6.37 to -0.76, I²=97.2%; four studies, n=306), B-type natriuretic peptide (WMD -83.17 picograms/mL, 95% CI -121.29 to -45.05, I² =96.3%; four studies, n=215) and New York Heart Association functional class (WMD -0.30, 95% CI -0.37 to -0.23, I²=72.4%; three studies, n=160) compared to control conditions.

Meta-regression showed that duration of follow-up was significantly associated with LVEF functioning (p=0.03). Sensitivity analysis that excluded one high-quality long-term study resulted in no benefit of statin on LVEF functioning. Removal of two studies individually resulted in statin having no benefit on LVEDD and LVESD. There was no evidence of publication bias.

Authors' conclusions

Statin treatment might increase LVEF in chronic heart failure patients, although this may be time dependent. Statin may also reduce LVEDD, LVESD, B-type natriuretic peptide and New York Heart Association functional class in patients with chronic heart failure.

CRD commentary

The review addressed a clear question with well-defined inclusion criteria. No information was provided on control conditions included in the review. A suitable search was carried out. Appropriate steps were taken to reduce risks of language and publication biases. Publication bias was assessed and ruled out. Steps were taken during study selection, data extraction and quality assessment to minimise risks of reviewer error and bias. Study quality was assessed. Most of the included studies were of moderate to low quality. Suitable analyses were carried out. Statistical heterogeneity was investigated using appropriate analyses and found to be high. Single studies were responsible for significant effects for some outcomes. Most participants had normal LDL levels and the extent to which the findings could be generalised to patients with high LDL was unclear.

Given the low quality of included studies and presence of statistical heterogeneity, the authors' conclusions should be treated with caution.

Implications of the review for practice and research

Practice: The authors stated that statin may be a potential novel treatment for chronic heart failure patients.

Research: The authors did not state any implications for research.

Funding

Key Projects in the National Science and Technology Pillar Program in the Eleventh Five-Year Plan Period (No. 2006BAI01A04); National Natural Science Foundation of China (No. 30871073); National High-Tech Research and Development Program of China (No. 2006AA02A406); Outstanding Youth Grant from National Natural Science Foundation of China (No. 30725036).

Bibliographic details

Zhang L, Zhang S, Jiang H, Sun A, Zou Y, Ge J. Effects of statin treatment on cardiac function in patients with chronic heart failure: a meta-analysis of randomized controlled trials. Clinical Cardiology 2011; 34(2): 117-123. [PMC free article: PMC6652713] [PubMed: 21298656]

Original Paper URL

http://onlinelibrary.wiley.com/doi/10.1002/clc.20821/abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Aged; Anticholesteremic Agents /therapeutic use; Cholesterol /blood; Cytokines; Female; Heart Failure /blood /drug therapy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors /therapeutic use; Male; Middle Aged; Natriuretic Peptide, Brain; Neurotransmitter Agents; Oxidative Stress; Randomized Controlled Trials as Topic; Stroke Volume /drug effects; Ventricular Function, Left /drug effects; Ventricular Remodeling /drug effects

AccessionNumber

12011001547

Database entry date

09/11/2011

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.