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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.

Abstract

BACKGROUND

Therapy guided by N-terminal-pro-B-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. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP-guided treatment strategy.

METHODS AND RESULTS

Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged≥60 years with left ventricular ejection fraction≤45% to intensified, NT-proBNP-guided versus standard, symptom-guided therapy into prespecified age groups (60-74 and ≥75 years) during 18 months. A total of 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. During long-term, NT-proBNP-guided therapy did not improve hospital-free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71-1.06; P=0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64-1.13; P=0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55-0.90; P=0.005). Patients aged 60 to 74 years had benefit from NT-proBNP-guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged≥75 years did not (P<0.10 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 end point compared with symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. 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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Cardiology, Maastricht University Medical Center, CARIM, Maastricht, The Netherlands.

    , , , , , , , , ,

    Source

    Circulation. Heart failure 7:1 2014 Jan pg 131-9

    MeSH

    Adrenergic beta-Antagonists
    Aged
    Aged, 80 and over
    Angiotensin Receptor Antagonists
    Angiotensin-Converting Enzyme Inhibitors
    Biomarkers
    Disease Management
    Endpoint Determination
    Female
    Follow-Up Studies
    Heart Failure
    Humans
    Longitudinal Studies
    Male
    Middle Aged
    Mineralocorticoid Receptor Antagonists
    Natriuretic Peptide, Brain
    Peptide Fragments
    Renin-Angiotensin System
    Stroke Volume
    Survival Rate
    Symptom Assessment

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24352403

    Citation

    Sanders-van Wijk, Sandra, et al. "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." Circulation. Heart Failure, vol. 7, no. 1, 2014, pp. 131-9.
    Sanders-van Wijk S, Maeder MT, Nietlispach F, et al. 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. Circ Heart Fail. 2014;7(1):131-9.
    Sanders-van Wijk, S., Maeder, M. T., Nietlispach, F., Rickli, H., Estlinbaum, W., Erne, P., ... Brunner-La Rocca, H. P. (2014). 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. Circulation. Heart Failure, 7(1), pp. 131-9. doi:10.1161/CIRCHEARTFAILURE.113.000527.
    Sanders-van Wijk S, et al. 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. Circ Heart Fail. 2014;7(1):131-9. PubMed PMID: 24352403.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Sanders-van Wijk,Sandra, AU - Maeder,Micha T, AU - Nietlispach,Fabian, AU - Rickli,Hans, AU - Estlinbaum,Werner, AU - Erne,Paul, AU - Rickenbacher,Peter, AU - Peter,Martin, AU - Pfisterer,Matthias P, AU - Brunner-La Rocca,Hans-Peter, AU - ,, Y1 - 2013/12/18/ PY - 2013/12/20/entrez PY - 2013/12/20/pubmed PY - 2014/5/28/medline KW - aging KW - heart failure KW - pro-brain natriuretic peptide (1–76) KW - prognosis KW - type-B natriuretic peptide SP - 131 EP - 9 JF - Circulation. Heart failure JO - Circ Heart Fail VL - 7 IS - 1 N2 - BACKGROUND: Therapy guided by N-terminal-pro-B-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. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP-guided treatment strategy. METHODS AND RESULTS: Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged≥60 years with left ventricular ejection fraction≤45% to intensified, NT-proBNP-guided versus standard, symptom-guided therapy into prespecified age groups (60-74 and ≥75 years) during 18 months. A total of 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. During long-term, NT-proBNP-guided therapy did not improve hospital-free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71-1.06; P=0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64-1.13; P=0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55-0.90; P=0.005). Patients aged 60 to 74 years had benefit from NT-proBNP-guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged≥75 years did not (P<0.10 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 end point compared with symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. 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. SN - 1941-3297 UR - https://www.unboundmedicine.com/medline/citation/24352403/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_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCHEARTFAILURE.113.000527?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -