Cost-effectiveness of N-terminal pro-B-type natriuretic-guided therapy in elderly heart failure patients: results from TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure).

This study aimed to assess cost-effectiveness of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided versus symptom-guided therapy in heart failure (HF) patients ≥60 years old. Cost-effectiveness of NT-proBNP guidance in HF patients is unclear. It may create additional costs with uncertain benefits. In the TIME-CHF (Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure), patients with left ventricular ejection fraction (LVEF) of ≤45% were randomized to receive intensified NT-proBNP-guided therapy or standard, symptom-guided therapy. For cost-effectiveness analysis, 467 (94%) patients (age 76 ± 7 years, 66% male) were eligible. Incremental cost-effectiveness was calculated as incremental costs per gained life-year and quality-adjusted life-year (QALY) within the 18-month trial period, as defined per protocol. NT-proBNP-guided therapy was dominant (i.e., more effective and less costly) over symptom-guided therapy, saving $2,979 USD (2.5 to 97.5% confidence interval [CI]: $8,758 to $3,265) per patient, with incremental effectiveness of +0.07 life-years and +0.05 QALYs. The probability of NT-proBNP-guided therapy being dominant was 80%, and the probability of saving 1 life-year or QALY at a cost of $50,000 was 97% and 93%, respectively. Exclusion of residence costs resulted in an incremental cost-effectiveness ratio (ICER) of $5,870 per life-year gained. Cost-effectiveness of NT-proBNP-guided therapy was most pronounced in patients <75 years old and in those with <2 significant comorbidities, being dominant in all sensitivity analyses. In the worst-case scenario (excluding residence costs in those with ≥2 comorbidities), the ICER was $11,935 per life-year gained. NT-proBNP-guided therapy has a high probability of being cost effective in HF patients with reduced LVEF, particularly in patients age 60 to 75 years or with less than 2 comorbidities. (Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure [TIME-CHF]; ISRCTN43596477).

Sanders-van Wijk S ，van Asselt AD ，Rickli H ，Estlinbaum W ，Erne P ，Rickenbacher P ，Vuillomenet A ，Peter M ，Pfisterer ME ，Brunner-La Rocca HP ，TIME-CHF Investigators ... -  《-》

Long-term results of intensified, N-terminal-pro-B-type natriuretic peptide-guided versus symptom-guided treatment in elderly patients with heart failure: five-year follow-up from TIME-CHF.

Sanders-van Wijk S ，Maeder MT ，Nietlispach F ，Rickli H ，Estlinbaum W ，Erne P ，Rickenbacher P ，Peter M ，Pfisterer MP ，Brunner-La Rocca HP ，TIME-CHF Investigators ... -  《-》

N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF).

Maeder MT ，Rickenbacher P ，Rickli H ，Abbühl H ，Gutmann M ，Erne P ，Vuilliomenet A ，Peter M ，Pfisterer M ，Brunner-La Rocca HP ，TIME-CHF Investigators ... -  《-》

Safety and tolerability of intensified, N-terminal pro brain natriuretic peptide-guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME-CHF.

Sanders-van Wijk S ，Muzzarelli S ，Neuhaus M ，Kiencke S ，Maeder M ，Estlinbaum W ，Tobler D ，Mayer K ，Erne P ，Pfisterer ME ，Brunner-La Rocca HP ，TIME-CHF investigators ... -  《-》

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

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. 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 ≥I,I 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 NT-proBNP-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 ≥2 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 ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively). NT-proBNP-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. isrctn.org, identifier: ISRCTN43596477.

Davarzani N ，Sanders-van Wijk S ，Karel J ，Maeder MT ，Leibundgut G ，Gutmann M ，Pfisterer ME ，Rickenbacher P ，Peeters R ，Brunner-la Rocca HP ... -  《-》