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Effect of age and sex on efficacy and tolerability of ? blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

ABSTRACT: To determine the efficacy and tolerability of ? blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.13,833 patients from 11 trials; median age 64; 24% women.The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.Compared with placebo, ? blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by ? blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give ? blockers, 15.6% in those receiving placebo).Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive ? blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.

SUBMITTER: Kotecha D

PROVIDER: S-EPMC4849174 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

Kotecha Dipak D Manzano Luis L Krum Henry H Rosano Giuseppe G Holmes Jane J Altman Douglas G DG Collins Peter D PD Packer Milton M Wikstrand John J Coats Andrew J S AJ Cleland John G F JG Kirchhof Paulus P von Lueder Thomas G TG Rigby Alan S AS Andersson Bert B Lip Gregory Y H GY van Veldhuisen Dirk J DJ Shibata Marcelo C MC Wedel Hans H Böhm Michael M Flather Marcus D MD

BMJ (Clinical research ed.) 20160420

<h4>Objectives</h4>To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.<h4>Design</h4>Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.<h4>Participants</h4>13,833 patients from 11 trials; median age 64; 24% ...[more]

PMID: 27098105

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Project description:BackgroundLifetime risk of heart failure has been estimated to range from 20% to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2 HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF), are not known.MethodsParticipant-level data from 2 large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF ≥45%) and HFrEF (EF <45%) were determined at different index ages with the use of a modified Kaplan-Meier method with mortality and the other HF subtype as competing risks.ResultsWe included 12 417 participants >45 years of age (22.2% blacks, 44.8% men) who were followed up for median duration of 11.6 years with 2178 overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the index age of 45 years, the lifetime risk for any HF through 90 years of age was higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the lifetime risk for HFpEF was similar in men and women. In race-stratified analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9% versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar across the 2 groups. Among participants with antecedent myocardial infarction before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to 2.5-fold and 4-fold higher, respectively, compared with those without antecedent myocardial infarction.ConclusionsLifetime risks for HFpEF and HFrEF vary by sex, race, and history of antecedent myocardial infarction. These insights into the distribution of HF risk and its subtypes could inform the development of targeted strategies to improve population-level HF prevention and control.

Project description:BackgroundThe evidence-based beta-blockers carvedilol, bisoprolol, and metoprolol succinate reduce mortality and hospitalizations among patients with heart failure with reduced ejection fraction (HFrEF). Use of these medications is not well described in the general population of patients with HFrEF, especially among patients with potential contraindications.ObjectivesOur goal was to describe the patterns of prescription fills for carvedilol, bisoprolol, and metoprolol succinate among Medicare beneficiaries hospitalized for HFrEF, as well as to estimate the associations between specific contraindications for beta-blocker therapy and those patterns.Methods and resultsWith the use of the cohort of 15,205 Medicare beneficiaries hospitalized for HFrEF from 2007 to 2013 in the 5% Medicare random sample, we described prescription fills (30 days after discharge) and dosage patterns (1 year after discharge) for beta-blockers. By means of of Fine and Gray competing risk models, we estimated the associations between potential contraindications (hypotension, chronic obstructive pulmonary disease [COPD], asthma, and syncope) and prescription fill and dosing patterns while adjusting for demographics, comorbidities, and health care utilization. For beneficiaries who did not die or readmitted to the hospital, 38% of hospitalizations were followed by a prescription fill for an evidence-based beta-blocker within 30 days, 12% were followed by prescription fills for at least 50% of the recommended dose of an evidence-based beta-blocker within 1 year, and 9% were followed by a prescription fill for an up-titrated dose of an evidence-based beta-blocker within 1 year. The prevalence of the contraindications were 21% for hypotension, 48% for COPD, 15% for asthma, and 12% for syncope. Among beneficiaries who did not fill a prescription for an evidence-based beta-blocker within 30 days, 67% had at least 1 of these contraindications. Hypotension, COPD, and syncope were each associated with a ∼10% lower risk of filling a prescription for an evidence-based beta-blocker.ConclusionsPrescription fill and up-titration rates for evidence-based beta-blockers are low among Medicare beneficiaries with HFrEF, but contraindications explain only a minor part of these low rates.

Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.

Dataset Information

Effect of age and sex on efficacy and tolerability of ? blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

Publications

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis.

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