Gianluigi Savarese1, Nicola Orsini2, Camilla Hage3, Ola Vedin4, Francesco Cosentino5, Giuseppe M C Rosano6, Ulf Dahlström7, Lars H Lund5. 1. Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: gianluigi.savarese@ki.se. 2. Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. 3. Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Department of Medical Sciences, Uppsala University and Uppsala Clinical Research Center, Uppsala, Sweden. 5. Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden. 6. Cardiovascular and Cell Sciences Research Institute, St. George's University, London, United Kingdom; Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy. 7. Department of Cardiology, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Abstract
OBJECTIVES: The purpose of this study was to assess the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiovascular (CV) versus non-CV events and between NT-proBNP and potential treatment effects in heart failure (HF) with preserved, mid-range, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF, respectively) and clinically relevant subgroups. BACKGROUND: Optimizing patient eligibility criteria in HF trials requires biomarkers that enrich for CV but not for non-CV events and select patients most likely to respond to the tested intervention. METHODS: In the Swedish HF registry population stratified by EF category, we used Kaplan-Meier curves to estimate unadjusted CV and non-CV risks (mortality or hospitalization); Poisson regressions to calculate crude event rates of CV and non-CV events according to NT-proBNP levels; and Cox regressions to calculate the adjusted hazard ratios for HF therapies according to NT-proBNP ≤ or > median. RESULTS: In a cohort of 15,849 patients (23% HFpEF, 21% HFmrEF, 56% HFrEF), median NT-proBNP was 2,037, 2,192, and 3,141 pg/ml, respectively. With increasing NT-proBNP, CV event rates increased more steeply than non-CV rates (range 20 to 160 and 30 to 100 per 100 patient-years in HFpEF; 20 to 130 and 20 to 100 in HFmrEF; and 20 to 110 and 20 to 50 in HFrEF, respectively). The CV-to-non-CV ratio increased with increasing NT-proBNP in HFpEF and HFrEF, but only in the lower range in HFmrEF. The association between treatments (e.g., angiotensin-converting enzyme-inhibitor, angiotensin II receptor blockers, and beta-blockers) and outcomes was consistent in NT-proBNP ≤ and > median. CONCLUSIONS: In HF trial design in different EF categories, NT-proBNP may be a useful tool for eligibility and enrichment for CV events, but its role in predicting a potential treatment response remains unclear.
OBJECTIVES: The purpose of this study was to assess the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiovascular (CV) versus non-CV events and between NT-proBNP and potential treatment effects in heart failure (HF) with preserved, mid-range, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF, respectively) and clinically relevant subgroups. BACKGROUND: Optimizing patient eligibility criteria in HF trials requires biomarkers that enrich for CV but not for non-CV events and select patients most likely to respond to the tested intervention. METHODS: In the Swedish HF registry population stratified by EF category, we used Kaplan-Meier curves to estimate unadjusted CV and non-CV risks (mortality or hospitalization); Poisson regressions to calculate crude event rates of CV and non-CV events according to NT-proBNP levels; and Cox regressions to calculate the adjusted hazard ratios for HF therapies according to NT-proBNP ≤ or > median. RESULTS: In a cohort of 15,849 patients (23% HFpEF, 21% HFmrEF, 56% HFrEF), median NT-proBNP was 2,037, 2,192, and 3,141 pg/ml, respectively. With increasing NT-proBNP, CV event rates increased more steeply than non-CV rates (range 20 to 160 and 30 to 100 per 100 patient-years in HFpEF; 20 to 130 and 20 to 100 in HFmrEF; and 20 to 110 and 20 to 50 in HFrEF, respectively). The CV-to-non-CV ratio increased with increasing NT-proBNP in HFpEF and HFrEF, but only in the lower range in HFmrEF. The association between treatments (e.g., angiotensin-converting enzyme-inhibitor, angiotensin II receptor blockers, and beta-blockers) and outcomes was consistent in NT-proBNP ≤ and > median. CONCLUSIONS: In HF trial design in different EF categories, NT-proBNP may be a useful tool for eligibility and enrichment for CV events, but its role in predicting a potential treatment response remains unclear.
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