Importance The US Food and Drug Administration (FDA) expanded labeling for sacubitril/valsartan for use in individuals with chronic heart failure (HF) with left ventricular ejection fraction (LVEF) lower than normal. The population-level implications of implementation of sacubitril/valsartan at higher LVEF ranges is unknown. While the Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction (PARAGON-HF) trial did not meet its primary end point, the trial may provide useful information in projecting expected clinical events among treated individuals.

Objective To quantify newly eligible treatment candidates for sacubitril/valsartan under the expanded FDA labeling and to apply treatment effects and the number needed to treat (NNT) to prevent 1 worsening HF event derived from subgroups of the PARAGON-HF trial who fall under the revised FDA label.

Design, Setting, and Participants Newly eligible treatment candidates were estimated by mapping the LVEF distribution from 559 520 adult patients hospitalized between 2014 and 2019 in the Get With The Guidelines–Heart Failure registry to adults self-identifying with HF in the National Health and Nutrition Examination Survey (2015 to 2018). The NNT with 3 years of treatment for 3 end points of interest (total HF hospitalizations, total HF hospitalizations and cardiovascular death, and total HF hospitalizations and urgent HF visits and cardiovascular death) were estimated from the PARAGON-HF trial. Data were analyzed from February to June 2021.

Main Outcomes and Measures Number of worsening HF events prevented or postponed if eligible patients were treated with sacubitril/valsartan for 3 years.

Results Of an estimated 4 682 098 adults, the mean (SE) age was 66.3 (0.8) years, 1 995 037 (42.6%) were women, and 748 045 (16.0%) were Black. The potential number of adults projected to be newly eligible varied by the definition of FDA labeling of lower than normal LVEF from 643 161 (95% CI, 534 433-751 888; LVEF of 41% to 50%) to 1 838 756 (95% CI, 1 527 911-2 149 601; LVEF of 41% to 60%). In the PARAGON-HF trial, the NNT to prevent a worsening HF event (range, 7 to 12 patients) was consistent irrespective of specific LVEF range selected. Comprehensive implementation of sacubitril/valsartan among newly eligible patients was empirically estimated to prevent up to 69 268 (95% CI, 57 558-80 978) worsening HF events (LVEF of 41% to 50%) to 182 592 (95% CI, 151 725-213 460) worsening HF events (LVEF of 41% to 60%).

Conclusions and Relevance The expanded FDA labeling is positioned to substantially increase the potential HF population eligible for sacubitril/valsartan by up to 1.8 million individuals and has the potential to prevent or postpone as many as 180 000 worsening HF events, depending on the definition of normal LVEF.

重要性 美国食品和药物管理局 (FDA) 扩大了沙库巴曲/缬沙坦的标签，用于左心室射血分数 (LVEF) 低于正常值的慢性心力衰竭 (HF) 患者。在较高的 LVEF 范围内实施沙库巴曲/缬沙坦对人群的影响尚不清楚。虽然 ARNI 与 ARB 保留射血分数的 HF 全球结果的前瞻性比较 (PARAGON-HF) 试验未达到其主要终点，但该试验可能为预测治疗个体的预期临床事件提供有用的信息。

目的 量化 FDA 扩展标签下新符合条件的沙库巴曲/缬沙坦治疗候选者，并应用治疗效果和需要治疗的数量 (NNT) 以防止 1 起来自 PARAGON-HF 试验亚组的恶化 HF 事件属于修订版FDA 标签。

设计、设置和参与者 通过将 2014 年至 2019 年间住院的 559 520 名成年患者的 LVEF 分布映射到“获取指南-心力衰竭”登记处与国家健康和营养中自我识别为 HF 的成年人的 LVEF 分布，估计了新的合格治疗候选者考试调查（2015 年至 2018 年）。从 PARAGON-HF 试验估计了对 3 个终点（总 HF 住院、总 HF 住院和心血管死亡，以及总 HF 住院和紧急 HF 就诊和心血管死亡）治疗 3 年的 NNT。数据分析时间为 2021 年 2 月至 2021 年 6 月。

主要结果和措施 如果符合条件的患者接受沙库巴曲/缬沙坦治疗 3 年，可预防或推迟恶化的 HF 事件数。

结果 在估计的 4 682 098 名成年人中，平均 (SE) 年龄为 66.3 (0.8) 岁，1 995 037 (42.6%) 为女性，748 045 (16.0%) 为黑人。预计新符合条件的成年人的潜在数量因 FDA 标签低于正常 LVEF 的定义而异，从 643 161（95% CI，534 433-751 888；LVEF 为 41% 至 50%）到 1 838 756（95 % CI，1 527 911-2 149 601；LVEF 为 41% 至 60%）。在 PARAGON-HF 试验中，无论选择何种特定 LVEF 范围，用于预防 HF 事件恶化（范围为 7 至 12 名患者）的 NNT 都是一致的。经验估计，在新符合条件的患者中全面实施沙库巴曲/缬沙坦可预防多达 69 268 (95% CI，57 558-80 978) 至 182 592 (95% CI， 151 725-213 460) 心衰事件恶化（LVEF 为 41% 至 60%）。

结 _左室射血分数。