Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: The PARADIGM-HF trial
Vardeny, Orly, Claggett, Brian L., Packer, Milton, Zile, Michael R., Rouleau, Jean L., Swedberg, Karl, Teerlink, John R., Desai, Akshay S., Lefkowitz, Martin P., Shi, Victor C., McMurray, John J. V. and Solomon, Scott D.. (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. https://doi.org/10.1002/ejhf.580
|Authors||Vardeny, Orly, Claggett, Brian L., Packer, Milton, Zile, Michael R., Rouleau, Jean L., Swedberg, Karl, Teerlink, John R., Desai, Akshay S., Lefkowitz, Martin P., Shi, Victor C., McMurray, John J. V. and Solomon, Scott D.|
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.
|Keywords||chronic heart failure; neprilysin inhibitor; clinical trial; sacubitril; valsartan|
|Journal||European Journal of Heart Failure|
|Journal citation||18 (10), pp. 1228 - 1234|
|Publisher||John Wiley & Sons Ltd|
|Digital Object Identifier (DOI)||https://doi.org/10.1002/ejhf.580|
|Open access||Open access|
|Page range||1228 - 1234|
|Research Group||Mary MacKillop Institute for Health Research|
© 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
|Place of publication||United Kingdom|
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