[Show abstract][Hide abstract] ABSTRACT: Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.
Expert Review of Cardiovascular Therapy 07/2015; 13(7):799-809. DOI:10.1586/14779072.2015.1053872
[Show abstract][Hide abstract] ABSTRACT: With one possible exception, the last decade of clinical trials in hospitalized heart failure (HHF) patients has failed to demonstrate improvement in long-term clinical outcomes. This trend necessitates a need to evaluate optimal drug development strategies and standards of trial conduct. It has become increasingly important to recognize the heterogeneity among HHF patients and the differential characterization of novel drug candidates. Targeting these agents to specific subpopulations may afford optimal net response related to the particular mode of action of the drug. Analyses of previous trials demonstrate profound differences in the baseline characteristics of patients enrolled across global regions and participating sites. Such differences may influence risks for events and interpretation of results. Therefore, the actual execution of trials and the epidemiology of HHF populations at the investigative sites must be taken into consideration. Collaboration among participating sites including the provision of registry data tailored to the planned development program will optimize trial conduct. Observational data prior to study initiation may enable sites to feedback and engage in protocol development to allow for feasible and valid clinical trial conduct. This site-centered, epidemiology-based network environment may facilitate studies in specific patient populations and promote optimal data collection and clear interpretation of drug safety and efficacy. This review summarizes the roundtable discussion held by a multidisciplinary team of representatives from academia, National Institutes of Health, industry, regulatory agencies, payers, and contract and academic research organizations to answer the question: Who should be targeted for novel therapies in HHF?
[Show abstract][Hide abstract] ABSTRACT: -The prevalence of heart failure (HF) is expected to significantly rise unless high-risk patients are effectively screened and appropriate, cost-effective prevention interventions are implemented.
-We performed a systematic review to evaluate the prediction characteristics of the published HF risk prediction models as of August 2014 using MEDLINE and EMBASE databases. Eligible studies reported the development, validation, or impact assessment of a model. Two investigators performed independent review to extract data on study design and characteristics, risk predictors, discrimination, calibration, and reclassification ability of models, as well as validation and impact analysis. We included 13 publications reporting on 28 HF risk prediction models. Models had acceptable-to-good discriminatory ability (c-statistics >0.70) in the derivation sample. Calibration was less commonly assessed, but was acceptable when it was. Only two models were externally validated more than once, displaying modest-to-acceptable discrimination (c-statistics 0.61-0.79). When assessed, novel blood and imaging markers modestly improved risk prediction. One model assessed the prediction properties in race-based subgroups while two models evaluated gender-based subgroups. Impact analysis found none of the models recommended for use in any clinical practice guideline.
-Incident HF risk prediction remains at an early stage. The discrimination ability of current models is acceptable in derivation datasets but most models have not been externally validated. It remains unclear which models are cost-effective and best suit population screening needs. The attendant effects of models on clinical and preventative care requires further study.