PMID- 19176440 OWN - NLM STAT- MEDLINE DCOM- 20090204 LR - 20220317 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 301 IP - 4 DP - 2009 Jan 28 TI - BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. PG - 383-92 LID - 10.1001/jama.2009.2 [doi] AB - CONTEXT: It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy. OBJECTIVE: To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy. DESIGN, SETTING, AND PATIENTS: Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008. INTERVENTION: Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy). MAIN OUTCOME MEASURES: Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires. RESULTS: Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction) CONCLUSION: Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43596477. FAU - Pfisterer, Matthias AU - Pfisterer M AD - Department of Cardiology, University Hospital Basel, CH-4031 Basel, Switzerland. pfisterer@email.ch FAU - Buser, Peter AU - Buser P FAU - Rickli, Hans AU - Rickli H FAU - Gutmann, Marc AU - Gutmann M FAU - Erne, Paul AU - Erne P FAU - Rickenbacher, Peter AU - Rickenbacher P FAU - Vuillomenet, Andre AU - Vuillomenet A FAU - Jeker, Urs AU - Jeker U FAU - Dubach, Paul AU - Dubach P FAU - Beer, Hansjurg AU - Beer H FAU - Yoon, Se-Il AU - Yoon SI FAU - Suter, Thomas AU - Suter T FAU - Osterhues, Hans H AU - Osterhues HH FAU - Schieber, Michael M AU - Schieber MM FAU - Hilti, Patrick AU - Hilti P FAU - Schindler, Ruth AU - Schindler R FAU - Brunner-La Rocca, Hans-Peter AU - Brunner-La Rocca HP CN - TIME-CHF Investigators LA - eng SI - ISRCTN/ISRCTN43596477 PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Biomarkers) RN - 0 (Cardiovascular Agents) RN - 0 (Diuretics) RN - 0 (Nitrates) RN - 0 (Peptide Fragments) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 73K4184T59 (Digoxin) SB - IM CIN - JAMA. 2009 Jan 28;301(4):432-4. PMID: 19176447 CIN - JAMA. 2009 May 27;301(20):2091-2; author reply 2092-3. PMID: 19470982 CIN - JAMA. 2009 May 27;301(20):2091; author reply 2092-3. PMID: 19470983 CIN - Praxis (Bern 1994). 2009 Jul 29;98(15):845-6. PMID: 19642070 MH - Adrenergic beta-Antagonists/administration & dosage MH - Aged MH - Angiotensin Receptor Antagonists MH - Angiotensin-Converting Enzyme Inhibitors/administration & dosage MH - Biomarkers/blood MH - Cardiovascular Agents/*administration & dosage MH - Digoxin/administration & dosage MH - Disease-Free Survival MH - Diuretics/administration & dosage MH - Female MH - Germany MH - Heart Failure/*blood/*drug therapy/physiopathology MH - Humans MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Natriuretic Peptide, Brain/*blood/drug effects MH - Nitrates/administration & dosage MH - Odds Ratio MH - Peptide Fragments/*blood/drug effects MH - Proportional Hazards Models MH - *Quality of Life MH - Severity of Illness Index MH - Stroke Volume MH - Surveys and Questionnaires MH - Switzerland MH - Treatment Outcome FIR - Buser, P T IR - Buser PT FIR - Muzzarelli, S IR - Muzzarelli S FIR - Leibundgut, G IR - Leibundgut G FIR - Tobler, D IR - Tobler D FIR - Nietlispach, F IR - Nietlispach F FIR - Abbuhl, H IR - Abbuhl H FIR - Studer, D IR - Studer D FIR - Ehl, Niklas IR - Ehl N FIR - Osswald, S IR - Osswald S FIR - Schindler, R IR - Schindler R FIR - Vuillomenet, A IR - Vuillomenet A FIR - Wachter, M IR - Wachter M FIR - Paul, M IR - Paul M FIR - Steudter, E IR - Steudter E FIR - Popp, S IR - Popp S FIR - Schneiter, S IR - Schneiter S FIR - Mussio, P IR - Mussio P FIR - Julius, B IR - Julius B FIR - Beer, J IR - Beer J FIR - Neuhaus, M IR - Neuhaus M FIR - Lehmann, E IR - Lehmann E FIR - Hischier, D IR - Hischier D FIR - Sonntag, S IR - Sonntag S FIR - Jenny, D IR - Jenny D FIR - Suter, T IR - Suter T FIR - Suter, S IR - Suter S FIR - Rickenbacher, P IR - Rickenbacher P FIR - Kiencke, S IR - Kiencke S FIR - Kofmel, A IR - Kofmel A FIR - Handschin, R IR - Handschin R FIR - Dubach, P IR - Dubach P FIR - Oswald, U IR - Oswald U FIR - Meyer, K IR - Meyer K FIR - Fahrner, R IR - Fahrner R FIR - Hornig, B IR - Hornig B FIR - Leibundgut, G IR - Leibundgut G FIR - Estlinbaum, W IR - Estlinbaum W FIR - Gutmann, M IR - Gutmann M FIR - Pittl, U IR - Pittl U FIR - Jorg, L IR - Jorg L FIR - Voss, F IR - Voss F FIR - Kreuzer, S IR - Kreuzer S FIR - Pfluger, H IR - Pfluger H FIR - Osterhues, H H IR - Osterhues HH FIR - Kurz, S IR - Kurz S FIR - Erne, P IR - Erne P FIR - Zaker, R IR - Zaker R FIR - Studer, M IR - Studer M FIR - Khurana, K S IR - Khurana KS FIR - Auf der Maur, C IR - Auf der Maur C FIR - Schonenberger, R IR - Schonenberger R FIR - Jeker, U IR - Jeker U FIR - Hilti, P IR - Hilti P FIR - Gret, A IR - Gret A FIR - Schieber, M M IR - Schieber MM FIR - Bullinger, A IR - Bullinger A FIR - Sechtem, U IR - Sechtem U FIR - Rickli, H IR - Rickli H FIR - Mader, M IR - Mader M FIR - Steven, G IR - Steven G FIR - Hack, D IR - Hack D FIR - Weilenmann, D IR - Weilenmann D FIR - Schmied, C IR - Schmied C FIR - Ammann, P IR - Ammann P FIR - Yoon, S I IR - Yoon SI FIR - Zaker, R IR - Zaker R FIR - Khurana, K S IR - Khurana KS FIR - Krummenacher, V IR - Krummenacher V FIR - Toggwiler, S IR - Toggwiler S FIR - Peter, M IR - Peter M FIR - Zaker, R IR - Zaker R FIR - Toggwiler, S IR - Toggwiler S FIR - Khurana, K S IR - Khurana KS FIR - Jeker, U IR - Jeker U FIR - Beer, J IR - Beer J FIR - Brunner-La Rocca, H P IR - Brunner-La Rocca HP FIR - Buser, P T IR - Buser PT FIR - Dubach, P IR - Dubach P FIR - Erne, P IR - Erne P FIR - Estlinbaum, W IR - Estlinbaum W FIR - Hilti, P IR - Hilti P FIR - Osswald, S IR - Osswald S FIR - Osterhues, H H IR - Osterhues HH FIR - Peter, M IR - Peter M FIR - Pfisterer, M IR - Pfisterer M FIR - Rickenbacher, P IR - Rickenbacher P FIR - Rickli, H IR - Rickli H FIR - Schieber, M M IR - Schieber MM FIR - Suter, T IR - Suter T FIR - Vuillomenet, A IR - Vuillomenet A FIR - Yoon, S I IR - Yoon SI FIR - Pfisterer, M IR - Pfisterer M FIR - Brunner-La Rocca, H P IR - Brunner-La Rocca HP FIR - Kiowski, W IR - Kiowski W FIR - Follath, F IR - Follath F FIR - Burckhardt, D IR - Burckhardt D FIR - Schindler, R IR - Schindler R FIR - Harder-Allgower, A IR - Harder-Allgower A FIR - Wurst, H IR - Wurst H FIR - Wild, J IR - Wild J FIR - Brunner-La Rocca, H P IR - Brunner-La Rocca HP EDAT- 2009/01/30 09:00 MHDA- 2009/02/05 09:00 CRDT- 2009/01/30 09:00 PHST- 2009/01/30 09:00 [entrez] PHST- 2009/01/30 09:00 [pubmed] PHST- 2009/02/05 09:00 [medline] AID - 301/4/383 [pii] AID - 10.1001/jama.2009.2 [doi] PST - ppublish SO - JAMA. 2009 Jan 28;301(4):383-92. doi: 10.1001/jama.2009.2.