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IMPORTANCEThe natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ("guided therapy") with inconsistent results. OBJECTIVE To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). DESIGN, SETTINGS, AND PARTICIPANTSThe Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction Յ40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care.INTERVENTIONS Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. MAIN OUTCOMES AND MEASURESThe primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. RESULTSThe data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; (95% CI, 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. CONCLUSIONS AND RELEVANCEIn high-risk patients with HFrEF, a strategy of NT-proBNPguided therapy was not more effective than a usual care strategy in improving outcomes.

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Chronic heart failure (CHF) is highly prevalent in older individuals and a major cause of morbidity, mortality, hospitalizations and disability. Cardiac rehabilitation (CR) exercise training and CHF self-care counseling have each been shown to improve clinical status and clinical outcomes in CHF. Systematic reviews and meta-analyses of CR exercise training alone (without counseling) have demonstrated consistent improvements in CHF symptoms in addition to reductions of cardiac mortality and hospitalizations, although individual trials have been less conclusive of the latter two findings. The largest single trial, HF-ACTION, showed a reduction in the adjusted risk for the combined end point of all-cause mortality or hospitalization (HR: 0.89, 95% CI: 0.81-0.99; P=0.03). Quality of life and mental depression also improved. CHF-related counseling whether provided in isolation or in combination with CR exercise training improves clinical outcomes and reduces CHF-related hospitalizations We review current evidence on the benefits and risks of CR and self-care counseling in patients with CHF, provide recommendations for patient selection for third party payers, and discuss the role of CR in promoting self-care and behavioral changes.

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