Division of General Internal Medicine, University of California Los Angeles Medical Center, Los Angeles.
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
JAMA Cardiol. 2018 Dec 1;3(12):1226-1231. doi: 10.1001/jamacardio.2018.3957.
The addition of receptor-neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor neprilysin inhibitor (ARNI) therapy, and whether it merits widespread use among diverse subpopulations, has not been well described.
To calculate estimated 5-year number needed to treat (NNT) values overall and for different subpopulations for the Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) cohort.
DESIGN, SETTING, AND PARTICIPANTS: Overall and subpopulation 5-year NNT values were estimated for different end points using data from PARADIGM-HF, a double-blind, randomized trial of sacubitril-valsartan vs enalapril. This multicenter, international study included 8399 men and women with HFrEF (ejection fraction, ≤40%). The study began in December 2009 and ended in March 2014. Analyses began in March 2018.
Random assignment to sacubitril-valsartan or enalapril.
Cardiovascular death or HF hospitalization, cardiovascular death, and all-cause mortality.
The final cohort of 8399 individuals included 1832 women (21.8%) and 5544 white individuals (66.0%), with a mean (SD) age of 63.8 (11.4) years. The 5-year estimated NNT for the primary outcome of cardiovascular death or HF hospitalization with ARNI therapy incremental to ACEI therapy in the overall cohort was 14. The 5-year estimated NNT values were calculated for different clinically relevant subpopulations and ranged from 12 to 19. The 5-year estimated NNT for all-cause mortality in the overall cohort with ARNI incremental to ACEI was 21, with values ranging from 16 to 31 among different subgroups. Compared with imputed placebo, the 5-year estimated NNT for all-cause mortality with ARNI was 11. The 5-year estimated NNT values were also calculated for other HFrEF therapies compared with controls from landmark trials for all-cause mortality and were found to be 18 for ACEI, 24 for angiotensin receptor blockers, 8 for β-blockers, 15 for mineralocorticoid antagonists, 14 for implantable cardioverter defibrillator, and 14 for cardiac resynchronization therapy.
The 5-year estimated NNT with ARNI therapy incremental to ACEI therapy overall and for clinically relevant subpopulations of patients with HFrEF are comparable with those for well-established HF therapeutics. These data further support guideline recommendations for use of ARNI therapy among eligible patients with HFrEF.
与标准治疗（包括肾素-血管紧张素系统阻滞剂）相比，添加受体-脑啡肽酶抑制剂（ARNI）已被证明可改善射血分数降低的心力衰竭（HFrEF）患者的预后。ARNI 治疗的长期绝对风险降低，以及它是否值得在不同亚人群中广泛使用，尚未得到很好的描述。
使用 Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) 队列研究的数据，计算不同亚人群中总体和不同亚人群中不同终点的估计 5 年需要治疗人数（NNT）值。
设计、地点和参与者：使用来自 PARADIGM-HF 的数据，通过双盲、随机试验比较 sacubitril-valsartan 与依那普利，估计了不同结局的总体和亚人群的 5 年 NNT 值。这项多中心、国际研究纳入了 8399 名 HFrEF（射血分数，≤40%）男性和女性。该研究于 2009 年 12 月开始，2014 年 3 月结束。分析于 2018 年 3 月开始。
随机分配接受 sacubitril-valsartan 或依那普利治疗。
心血管死亡或心力衰竭住院、心血管死亡和全因死亡率。
最终的 8399 名个体队列包括 1832 名女性（21.8%）和 5544 名白人（66.0%），平均（SD）年龄为 63.8（11.4）岁。在整个队列中，与 ACEI 治疗相比，ARNI 治疗增加的主要终点为心血管死亡或心力衰竭住院的 5 年估计 NNT 值为 14。还为不同的临床相关亚人群计算了 5 年估计 NNT 值，范围为 12 至 19。在整个队列中，与 ACEI 相比，ARNI 增加的全因死亡率的 5 年估计 NNT 值为 21，不同亚组的范围为 16 至 31。与推断的安慰剂相比，ARNI 全因死亡率的 5 年估计 NNT 值为 11。还为来自全因死亡率的标志性试验的其他 HFrEF 治疗方法与对照进行了 5 年估计 NNT 值计算，发现 ACEI 为 18，血管紧张素受体阻滞剂为 24，β受体阻滞剂为 8，盐皮质激素拮抗剂为 15，植入式心脏复律除颤器为 14，心脏再同步治疗为 14。
与标准治疗（包括肾素-血管紧张素系统阻滞剂）相比，添加受体-脑啡肽酶抑制剂（ARNI）治疗可改善射血分数降低的心力衰竭（HFrEF）患者的预后。与已确立的心力衰竭治疗方法相比，在整个 HFrEF 患者亚人群中，使用 ARNI 治疗的 5 年估计 NNT 值相当。这些数据进一步支持指南建议在有资格的 HFrEF 患者中使用 ARNI 治疗。
