Rationale The ACCRUE (Meta-Analysis of Cell-based CaRdiac research) may be the

Rationale The ACCRUE (Meta-Analysis of Cell-based CaRdiac research) may be the initial prospectively declared collaborative multinational data source including person data of sufferers (IPD) with ischemic cardiovascular disease treated with cell therapy. included changes in end-diastolic volume (ΔEDV) end-systolic volume (ΔESV) and ejection fraction (ΔEF) analyzed with random-effects meta-analyses and analysis of covariance. We reported Khasianine weighted mean differences between cell therapy and control groups. No effect of cell therapy on MACCE (14.0% vs. 16.3% hazard ratio 0.86 95 0.63 or death (1.4% vs 2.1%) or death/re-AMI/stroke (2.9% vs 4.7%) was identified in comparison to controls. No change in ΔEF (mean difference: 0.96% 95 ?0.2;2.1) ΔEDV or ΔESV was observed compared to controls. These results were not influenced by anterior AMI location reduced baseline EF or the use of MRI for assessing left ventricular parameters. Conclusions This meta-analysis of IPD from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit in terms of clinical events or changes in left ventricular function. Khasianine statistics. Additional sensitivity analyses were performed to detect differences between studies. Two investigators conducted the analyses (EN MG). Investigation of heterogeneity and selection bias The statistics for investigating heterogeneity and selection bias of the included trials are presented in the Online Data Supplement. General statistics Normally-distributed continuous variables are presented as the mean±standard deviation (SD). Continuous parameters with skewed distributions are expressed as the median and first interquartile range. Binary and categorical variables are given as frequencies and percentages. Associations between the number of cells/log number of cells and the changes in EDV ESV or EF in the cell-treated group were calculated with linear regression analysis. All values were based on two-sided tests. For multiple comparisons values less than 0.01 were considered statistically significant. IPD meta-analysis All analyses were based on the intention to treat. Multiple Cox regression models were used to analyze the primary outcome stratified for the individual studies. The multiple model included cardiovascular prognostic factors for the occurrence of MACCE such as gender age diabetes mellitus (DM) hypertension hyperlipidemia and baseline EDV and EF values. This model was used to determine an adjusted common Khasianine treatment effect with baseline hazards that varied across studies.20 21 To evaluate possible dependencies of the treatment effect on other prognostic factors all possible interactions were tested within the multiple stratified Cox regression models. Factors were excluded from the analysis when data were missing in at least 50% of Khasianine cases (e.g. positive family anamnesis for heart disease baseline infarct size). Adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) are presented with the corresponding values. The Kaplan-Meier method and cumulative hazards CACNA1G were used to display the MACCE-free death-free death/re-AMI/stroke-free and TVR-free survival rates. Pre-specified subgroup analyses for the primary endpoint and the secondary endpoint of death/re-AMI/stroke were carried out for the following subgroup categories: age (> or ≤ 57 years) EF (> or ≤45%) baseline EDV (> or ≤130 ml) anterior AMI (yes or no) maximal creatine kinase (CK > or ≤ 3450 U/l; CK is associated with infarct size; 3450 U/L was the median value for all patients) gender DM hypertension hyperlipidemia smoking and use of MRI. The secondary endpoints changes in LV EF EDV and ESV were evaluated with an analysis of covariance (ANCOVA). The treatment effect was adjusted for cardiovascular risk factors male gender mode of measuring LV function anterior location of AMI baseline EDV baseline EF and time between AMI and randomization (sham intervention in controls or cell therapy in cell-treated groups); for these adjustments the individual studies were considered a block factor. Possible interacting effects with treatment were tested within these ANCOVA models. Changes in EDV ESV and EF in the cell therapy and control groups are expressed as mean±SD; the mean difference from baseline was reported with the standard error (SE) and the relative 95% CIs were reported as effect measures. Pre-specified subgroup analyses included the effect of FUP time and the effect of baseline EF on changes in LV function evaluated as dichotomous.