Long-term Results of Intensified, NT-proBNP-guided versus Symptom-guided Treatment in Elderly Patients with Heart Failure: 5-year Follow-up from TIME-CHF

Background —Therapy guided by N-terminal-proB-type natriuretic peptide (NT-proBNP) levels may improve outcomes in patients with chronic heart failure (HF), especially in younger patients with reduced left-ventricular ejection fraction (LVEF). It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP guided treatment strategy. Methods and Results —TIME-CHF randomized 499 HF patients aged ≥60years with LVEF≤45% to intensified, NT-proBNP-guided versus standard, symptom-guided therapy into pre-specified age groups (60-74y and ≥75y) during 18 months. 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF medication was intensified to a larger extent in the NT-proBNP-guided group. Over long-term, NT-proBNP-guided therapy did not improve hospital-free (1° endpoint: HR=0.87, 95%-CI 0.71-1.06; p=0.16) or overall survival (HR=0.85, 95%-CI 0.64-1.13; p=0.25) but did improve HF hospitalization-free survival (HR=0.70, 95%-CI, 0.55-0.90; p=0.005). Patients aged 60-74y had benefit from NT-proBNP-guided therapy regarding the primary endpoint and HF hospitalization-free survival whereas patients aged ≥75y did not (P<.10 for interaction). In landmark analysis, there was no regression to the mean after cessation of the NT-proBNP-guided strategy. More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival. Conclusions —Intensified, NT-proBNP-guided therapy did not improve the primary endpoint compared to symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60-74y, it improved clinical outcome including the primary endpoint. These effects did not disappear after cessation of the NT-proBNP-guided strategy on the long-term. This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP-guided group. Clinical Trial Registration —URL: http://www.isrctn.org. Unique identifier: [ISRCTN43596477][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN43596477