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Gender and Survival in Patients With Heart Failure

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Gender and Survival in Patients With Heart Failure

Methods


The methods and main results from the MAGGIC meta-analysis have already been described. In brief, we searched online databases using the key words: incidence, prognosis, outcome, mortality, clinical trials, HF, ventricle, EF, systolic, and diastolic. We also searched reference lists of articles obtained during the online search, as well as conference abstracts, and utilized personal communication. Eligible studies were those that included patients with HF and reported outcome (death from any cause). Studies that applied a left ventricular EF entry criterion were excluded. The meta-analysis was approved by The University of Auckland Human Subjects Ethics Committee.

Fifty-six potentially suitable studies were identified, and individual patient data were provided from 31 studies on a pre-defined set of variables including demographics, medical history, medical treatment, symptomatic status, clinical variables, laboratory variables, and outcome. Data from the individual studies were re-coded into a uniform format at the Central Co-ordinating Centre at the University of Auckland and incorporated into one database. The data from the Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) trial were made available for this meta-analysis, but the data set from this study was added at the London School of Hygiene and Tropical Medicine and the final analyses run again incorporating these data. The results from the MAGGIC meta-analysis demonstrated that patients with HF with preserved left ventricular EF have lower risk of death from any cause than patients with reduced left ventricular EF.

Statistical Analysis


For the current analyses, Cox proportional hazards models were used to estimate the risk of death from any cause within 3 years for men compared with women. All models were adjusted for age, aetiology (ischaemic vs. non-ischaemic), left ventricular EF [reduced (defined as EF <50%) vs. preserved], history of hypertension, diabetes, and atrial fibrillation, and stratified by study. Cox models adjusted for age were used to plot mortality curves.

Interactions between sex and the remaining covariates were explored. All covariates were dichotomous except for age, which was left as a continuous variable. Statistically significant interactions (interaction P-value <0.05) prompted subgroup analyses that focused on the relationship between sex and the covariate, within the EF group. For clarity, these models were only adjusted for age and stratified by study.

The correlation between scaled Schoenfeld residuals and length of follow-up showed that there was no violation of the proportional hazards assumption for all analyses. Analyses were performed using SAS v 9.2 (SAS Institute Inc., Cary, NC, USA).

Role of the Funding Source


The sponsors of the study had no role in the study design, data analysis or interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit the manuscript for publication.

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