Richard W Troughton1, Christopher M Frampton2, Hans-Peter Brunner-La Rocca3, Matthias Pfisterer4, Luc W M Eurlings3, Hans Erntell5, Hans Persson5, Christopher M O'Connor6, Deddo Moertl7, Patric Karlström8, Ulf Dahlström9, Hanna K Gaggin10, James L Januzzi10, Rudolf Berger11, A Mark Richards12, Yigal M Pinto13, M Gary Nicholls2. 1. Department of Medicine, University of Otago Christchurch, Christchurch Hospital, PO Box 4345, Christchurch 8140, New Zealand richard.troughton@cdhb.health.nz. 2. Department of Medicine, University of Otago Christchurch, Christchurch Hospital, PO Box 4345, Christchurch 8140, New Zealand. 3. Department of Cardiology Maastricht University Medical Center, Maastricht, The Netherlands. 4. Department of Cardiology, University Hospital Basel, Basel, Switzerland. 5. Department of Clinical Sciences, Karolinska Instutet, Danderyd Hospital, Stockholm, Sweden. 6. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. 7. Department of Cardiology, LKH, St Poelten, Austria. 8. Division of Cardiology, Department of Medicine, County Hospital Ryhov, Jonkoping, Sweden. 9. Department of Medical and Health Sciences, Linkoping University, Department of Cardiology, County Council of Ostergotland, Linkoping, Sweden. 10. Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. 11. Department of Cardiology, Medical University of Vienna, Vienna, Austria. 12. Department of Medicine, University of Otago Christchurch, Christchurch Hospital, PO Box 4345, Christchurch 8140, New Zealand National University Heart Centre Singapore, Singapore. 13. Academic Medical Center, Amsterdam, The Netherlands.
Abstract
AIMS: Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality. METHODS AND RESULTS: Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF. CONCLUSION: Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.
AIMS: Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality. METHODS AND RESULTS: Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF. CONCLUSION: Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.
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