Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy

Okumura, N. et al. (2016) Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy. Circulation: Heart Failure, 9(9), e003212. (doi: 10.1161/CIRCHEARTFAILURE.116.003212) (PMID:27618854)

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Abstract

Background—In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitor enalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. Methods and Results—We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no), and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose (≥50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. We analyzed the primary composite end point of cardiovascular death or heart failure hospitalization, as well as cardiovascular death. Most randomized patients (n=8399) were treated with a diuretic (80%) and β-blocker (93%); 47% of those taking a β-blocker were treated with ≥50% of the recommended dose. In addition, 4671 (56%) were treated with a mineralocorticoid receptor antagonist, 2539 (30%) with digoxin, and 1243 (15%) had a defibrillating device; 2640 (31%) had undergone coronary revascularization. Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval, 0.73–0.87; P<0.001) and for cardiovascular death was 0.80 (0.71–0.89; P<0.001). The effect of sacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death ranged from 0.75 to 0.89, with no treatment-by-subgroup interaction. Conclusions—The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previous coronary revascularization or β-blocker dose.

Item Type:Articles
Additional Information:<br>On behalf of the PARADIGM-HF Investigators and Committees*</br> *see Supplemental Appendix.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Okumura, Dr Naoki and Jhund, Dr Pardeep and McMurray, Professor John
Authors: Okumura, N., Jhund, P. S., Gong, J., Lefkowitz, M. P., Rizkala, A. R., Rouleau, J. L., Shi, V. C., Swedberg, K., Zile, M. R., Solomon, S. D., Packer, M., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Circulation: Heart Failure
Publisher:Lippincott Williams and Wilkins for the American Heart Association
ISSN:1941-3289
ISSN (Online):1941-3297
Published Online:12 September 2016
Copyright Holders:Copyright © 2016 American Heart Association, Inc.
First Published:First published in Circulation: Heart Failure 9(9):e003212
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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