N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations - Results From TIME-CHF

Background: Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N -Terminal B-type natriuretic peptide (NT-proBNP) guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis. Methods and Results: The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged >= 60 years, left ventricular ejection fraction <= 45%, New York Heart Association functional class to NT-proBNP guided versus symptom guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP guided, 55 symptom-guided) experienced 1 and 275 patients (133 NTproBNP guided, 142 symptom-guided) experienced >= 2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP guided, 65 symptom-guided) experienced events. NT-proBNP guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P =.01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P =.35). This was not the case regarding HF hospitalization events (HR 0.85 [P =.14] vs HR 0.73 [P =.01]) The beneficial effect of NT-proBNP guided therapy was seen only in patients aged < 75 years, and not in those aged years (interaction terms with P =.01 and P =.03 for all-cause hospitalization and HF hospitalization events, respectively). Conclusion: NT-prciBNP guided therapy reduces the risk of recurrent events in patients < 75 years of age. This included all-cause hospitalization by mainly reducing later events, adding knowledge to the neutral effect on this end point when shown using time-to-first-event analysis only.