Dataset Information

Discrepancies in autologous bone marrow stem cell trials and enhancement of ejection fraction (DAMASCENE): weighted regression and meta-analysis.

ABSTRACT:

Objective

To investigate whether discrepancies in trials of use of bone marrow stem cells in patients with heart disease account for the variation in reported effect size in improvement of left ventricular function.

Design

Identification and counting of factual discrepancies in trial reports, and sample size weighted regression against therapeutic effect size. Meta-analysis of trials that provided sufficient information.

Data sources

PubMed and Embase from inception to April 2013.

Eligibility for selecting studies

Randomised controlled trials evaluating the effect of autologous bone marrow stem cells for heart disease on mean left ventricular ejection fraction.

Results

There were over 600 discrepancies in 133 reports from 49 trials. There was a significant association between the number of discrepancies and the reported increment in EF with bone marrow stem cell therapy (Spearman's r=0.4, P=0.005). Trials with no discrepancies were a small minority (five trials) and showed a mean EF effect size of -0.4%. The 24 trials with 1-10 discrepancies showed a mean effect size of 2.1%. The 12 with 11-20 discrepancies showed a mean effect of size 3.0%. The three with 21-30 discrepancies showed a mean effect size of 5.7%. The high discrepancy group, comprising five trials with over 30 discrepancies each, showed a mean effect size of 7.7%.

Conclusions

Avoiding discrepancies is difficult but is important because discrepancy count is related to effect size. The mechanism is unknown but should be explored in the design of future trials because in the five trials without discrepancies the effect of bone marrow stem cell therapy on ejection fraction is zero.

SUBMITTER: Nowbar AN

PROVIDER: S-EPMC4002982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsThis study aimed to evaluate the clinical parameters including late gadolinium enhancement (LGE) of cardiovascular magnetic resonance to predict re-worsening of left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (DCM).Methods and resultsWe included 138 patients with recent-onset DCM who had an LVEF <45% and underwent LGE of cardiovascular magnetic resonance imaging at diagnosis and echocardiography at the yearly follow-up [median 6 (4-8.3) years]. Initial LVEF recovery was defined as LVEF increase >10% from baseline, resulting in LVEF ≧45% after treatment. The patients were divided into three groups: (i) improved (n = 83, 60%), defined as those with sustained LVEF ≧45%; (ii) re-worsening (n = 39, 28%), those with >5% decrease and LVEF <45% after the initial LVEF recovery; and (iii) not-improved (n = 16, 12%), those without initial LVEF recovery. The primary endpoint was a composite of hospitalization for heart failure or sudden cardiac death. In baseline, LGE was observed in 70 patients. The LGE area was significantly larger in the re-worsening and not-improved groups than that in the improved group (P < 0.001). Loess curves of long-term LVEF trajectories showed that LVEF in the re-worsening group increased in the first 2 years and slowly declined thereafter. Multivariate logistic regression analysis demonstrated that LGE area [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.03-1.16, P = 0.004], B-type natriuretic peptide (OR 1.49, 95% CI 1.05-2.21, P = 0.030) level at the initial recovery, and LVEF (OR 0.91, 95% CI 0.86-0.97, P = 0.004) at the initial LVEF recovery were independent predictors of re-worsening of LVEF. During a median follow-up of 2273 (interquartile range: 1634-3191) days, the primary endpoint was observed in 31 (22%) patients. Univariate Cox proportional hazards analysis demonstrated that the risk of experiencing the primary event in the re-worsening group was significantly higher (hazard ratio: 4.30, 95% CI 1.63-11.31, P = 0.003) than that in the improved group and was lower than that in the not-improved group (hazard ratio: 0.33, 95% CI 0.15-0.72, P = 0.006).ConclusionsRe-worsening of LVEF was observed in 28% of patients with recent-onset DCM who showed an initial improvement in LVEF. High LGE burden, higher B-type natriuretic peptide level, and lower LVEF at the initial LVEF recovery were independent predictors of re-worsening of LVEF in patients with DCM. Careful observation is recommended for patients with a high risk for re-worsening of LVEF, even in those with an initial LVEF recovery.