Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure Results of the initiation management predischarge: process for assessment of carvedilol therapy in heart failure (IMPACT-HF) trial

AbstractObjectivesThe Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial was an investigator-initiated study to evaluate if predischarge carvedilol initiation in stabilized patients hospitalized for heart failure (HF) increased the number of patients treated with beta-blockade at 60 days after randomization without increasing side effects or length of hospital stay.BackgroundBeta-blockers are underused in HF. Predischarge initiation may improve the use of evidence-based beta-blockade.MethodsThe IMPACT-HF was a prospective, randomized open-label trial conducted in 363 patients hospitalized for HF. Patients were randomized to carvedilol initiation pre-hospital discharge or to postdischarge initiation (>2 weeks) of beta-blockade at the physicians' discretion. The primary end point of the study was the number of patients treated with beta-blockade at 60 days after randomization. Secondary end points included the number of patients discontinuing beta-blockade, median dose achieved, and a composite of death, rehospitalization, unscheduled visit for HF, or ≥50% increase in oral diuretic, new oral diuretic, or any intravenous therapy with diuretics, inotropes, or other vasoactive agents.ResultsAt 60 days 165 patients (91.2%) randomized to predischarge carvedilol initiation were treated with a beta-blocker, compared with 130 patients (73.4%) randomized to initiation postdischarge (p < 0.0001). Predischarge initiation was not associated with an increased risk of serious adverse events. The median length of stay was five days in both groups.ConclusionsPredischarge initiation of carvedilol in stabilized patients hospitalized for HF improved the use of beta-blockade at 60 days without increasing side effects or length of stay. Predischarge initiation may be one approach to improve beta-blocker use in this population

Relationship of Serum Digoxin Concentration to Mortality and Morbidity in Women in the Digitalis Investigation Group Trial A Retrospective Analysis

ObjectivesThe purpose of this study was to investigate the relationship of serum digoxin concentration (SDC) and outcomes in women with heart failure (HF).BackgroundControversy continues concerning the clinical utility of digoxin in women with HF.MethodsOur analysis was retrospective with data from the Digitalis Investigation Group (DIG) trial. The principal study analysis reviewed 4,944 patients with HF due to systolic dysfunction who survived for at least 4 weeks (all 3,366 patients randomized to placebo and the 1,578 of 3,372 patients randomized to digoxin who had serum concentration measured 6 to 30 h [inclusive] after the last dose of study drug at 4 weeks).ResultsContinuous multivariable analysis demonstrated a significant linear relationship between SDC and mortality in women (p = 0.008) and men (p = 0.002, p = 0.766 for gender interaction). Averaging hazard ratios (HRs) across serum concentrations from 0.5 to 0.9 ng/ml in women produced a HR for death of 0.8 (95% confidence interval [CI] 0.62 to 1.13, p = 0.245) and for death or hospital stay for worsening HF of 0.73 (95% CI 0.58 to 0.93, p = 0.011). In contrast, SDCs from 1.2 to 2.0 ng/ml were associated with a HR for death for women of 1.33 (95% CI 1.001 to 1.76, p = 0.049).ConclusionsRetrospective analysis of data from the DIG trial indicates a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum concentrations ≥1.2 ng/ml seem harmful

Assessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment vs. risk aversion.

The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this framework raises questions as to whether requiring safety outcome studies for all new diabetes mellitus therapies remains justified. Given the burden of cardiovascular disease in patients with diabetes, the focus should shift towards cardiovascular outcome studies designed to evaluate efficacy (i.e. to determine the efficacy of a drug over placebo or standard care) rather than demonstrating that risk is not increased by a pre-specified safety margin. All stakeholders are responsible for ensuring that new drug approvals occur under conditions of appropriate safety and effectiveness. It is also a shared responsibility to avoid unnecessary hurdles that may compromise access to useful drugs and threaten the sustainability of health systems. It is critical to renew this debate so that stakeholders can collectively determine the optimal approach for developing new drugs to treat type 2 diabetes mellitus