Background: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients.

Methods and Results: We characterized patients in PARADIGM-HF by whether they reported hypotension during study run-in periods (enalapril, followed by sacubitril/valsartan) and after randomization and assessed whether hypotension modified the efficacy of sacubitril/valsartan. Of the 10 513 patients entering the enalapril run-in, 136 (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228 (2.4%) patients experienced hypotension and 51% were unable to successfully complete the run-in. After randomization, 388 (9.2%) participants had 501 hypotensive events with enalapril, and 588 (14.0%) participants had 803 hypotensive events with sacubitril/valsartan (P<0.001). There was no difference between randomized treatment groups in the number of participants who discontinued therapy because of hypotension. Individuals with a hypotensive event in either group were older, had lower blood pressure at randomization, and were more likely to have an implantable cardioverter defibrillator. Participants with hypotensive events during run-in who were ultimately randomized derived similar efficacy from sacubitril/valsartan compared with enalapril as those without hypotensive events (P interaction>0.90).

Conclusions: Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived similar benefit from sacubitril/valsartan compared with enalapril as those who did not experience hypotension.

背景：在PARADIGM-HF（血管紧张素受体中性溶酶抑制剂与血管紧张素转化酶抑制剂的前瞻性比较，以确定对心力衰竭的总体死亡率和发病率的影响）中，使用沙比特比/缬沙坦治疗心力衰竭可降低心血管死亡或心脏的主要复合结果与依那普利相比住院失败，但导致更多的症状性低血压。对低血压的关注可能会限制适当患者使用沙比特利/缬沙坦的使用。

方法和结果：我们对PARADIGM-HF患者的特征在于他们是否在研究进行期间（依那普利，随后是沙比特利/缬沙坦）和随机分组后报告了低血压，并评估了低血压是否改变了沙比特利/缬沙坦的疗效。在进入依那普利磨合的10 513名患者中，有136名（1.3％）经历了低血压，而93名（68％）无法继续进行下一阶段。在进入sacubitril / valsartan磨合期的9419名患者中，有228名（2.4％）患者经历了低血压，而51％的患者无法成功完成磨合。随机分组后，有388（9.2％）名受试者发生501例依那普利降压事件，而588（14.0％）名受试者发生803依库普利/缬沙坦降压事件（P<0.001）。随机治疗组之间因低血压而中断治疗的参与者人数没有差异。两组中发生降压事件的个体年龄较大，随机分组时血压较低，并且更有可能使用植入式心脏复律除颤器。最终被随机分组​​的有降压事件的参与者与依那普利相比，沙库比特/缬沙坦的疗效与无降压事件的参与者相似（P相互作用> 0.90）。

结论：相对于依那普利，降压素/缬沙坦相对于依那普利低血压更常见，但对永久性停药没有差异。与依那普利相比，磨合期低血压患者与依那普利相比，沙比特利/缬沙坦的获益与未经历低血压的患者相似。