Vardeny, O. et al. (2016) Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial. European Journal of Heart Failure, 18(10), pp. 1228-1234. (doi: 10.1002/ejhf.580) (PMID:27283779) (PMCID:PMC5095784)
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Abstract
Aims: In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. Methods and results: In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2–2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70–0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71–0.88, P < 0.001). Conclusions: In PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McMurray, Professor John |
| Authors: | Vardeny, O., Claggett, B., Packer, M., Zile, M. R., Rouleau, J., Swedberg, K., Teerlink, J. R., Desai, A. S., Lefkowitz, M., Shi, V., McMurray, J. J.V., and Solomon, S. D. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | European Journal of Heart Failure |
| Publisher: | Wiley |
| ISSN: | 1388-9842 |
| ISSN (Online): | 1879-0844 |
| Published Online: | 10 June 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in European Journal of Heart Failure 2016 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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