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Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.
- Source :
- European Journal of Heart Failure; Oct2016, Vol. 18 Issue 10, p1228-1234, 7p
- Publication Year :
- 2016
-
Abstract
- <bold>Aims: </bold>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.<bold>Methods and Results: </bold>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).<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- VALSARTAN
ENALAPRIL
DRUG efficacy
HEART failure treatment
TARGETED drug delivery
THERAPEUTICS
AMINOBUTYRIC acid
COMPARATIVE studies
DOSE-effect relationship in pharmacology
HEART failure
HETEROCYCLIC compounds
RESEARCH methodology
MEDICAL cooperation
RESEARCH
RESEARCH funding
EVALUATION research
RANDOMIZED controlled trials
BLIND experiment
ANGIOTENSIN receptors
STROKE volume (Cardiac output)
Subjects
Details
- Language :
- English
- ISSN :
- 13889842
- Volume :
- 18
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- European Journal of Heart Failure
- Publication Type :
- Academic Journal
- Accession number :
- 118527556
- Full Text :
- https://doi.org/10.1002/ejhf.580