Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.
Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.
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DOI：
10.1002/ejhf.580
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发表时间：
2016-10
影响因子：
18.2
通讯作者：
Solomon, Scott D.
中科院分区：
文献类型：
--
作者：
Vardeny, Orly;Claggett, Brian;Packer, Milton;Zile, Michael R.;Rouleau, Jean;Swedberg, Karl;Teerlink, John R.;Desai, Akshay S.;Lefkowitz, Martin;Shi, Victor;McMurray, John J. V.;Solomon, Scott D.
在这项分析中，我们利用来自PARADIGM-HF的数据来检验以下假设：在试验期间表现出任何剂量减少的受试者将从较低剂量的沙库巴曲/缬沙坦相对于较低剂量的依那普利中获得相似的益处。在PARADIGM-HF的事后分析中，我们通过患者在整个试验期间是否接受最大剂量（200 mg沙库巴曲/缬沙坦或10 mg依那普利，每日两次）或将剂量降低至较低剂量（100/50/0 mg沙库巴曲/缬沙坦或5/2.5/0 mg依那普利，每日两次）来表征患者。使用时间更新的考克斯回归模型，按剂量水平分层，估计主要结局的治疗效果。在两个治疗组中，剂量减少的受试者（43%的随机分配至依那普利组，42%的随机分配至沙库巴曲/缬沙坦组）具有相似的基线特征和相似的需要减少剂量的基线预测因子。在时间更新分析中，任何剂量降低均与主要事件的后续风险升高相关[风险比（HR）2.5，95%置信区间（CI）2.2-2.7]。然而，剂量减少后沙库巴曲/缬沙坦相对于依那普利的治疗获益（HR 0.80，95% CI 0.70-0.93，P < 0.001）与未经历任何剂量减少的患者中观察到的治疗获益（HR 0.79，95% CI 0.71-0.88，P < 0.001）相似。在PARADIGM-HF中，研究药物剂量减少识别出了重大心血管事件风险较高的患者。较低剂量沙库巴曲/缬沙坦患者相对于较低剂量依那普利患者的获益幅度与保持两种药物目标剂量的患者相似。
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. 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). 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.
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DOI：
10.1111/j.1751-7133.2011.00250.x
发表时间：
2012-01-01
期刊：
Congestive heart failure (Greenwich, Conn.)
影响因子：
--
作者：
Gheorghiade, Mihai;Albert, Nancy M;Fonarow, Gregg C
通讯作者：
Fonarow, Gregg C
DOI：
10.1016/s0735-1097(02)01970-8
发表时间：
2002-08-07
影响因子：
24
作者：
Wikstrand, J;Hjalmarson, Å;Wedel, H
通讯作者：
Wedel, H
影响因子：
18.2
作者：
McMurray, John J. V.;Packer, Milton;Zile, Michael R.
通讯作者：
Zile, Michael R.
影响因子：
13
作者：
Vardeny, Orly;Miller, Ryan;Solomon, Scott D.
通讯作者：
Solomon, Scott D.
影响因子：
2.8
作者：
Fonarow, Gregg C.;Abraham, William T.;Young, James B.
通讯作者：
Young, James B.