Department of Cardiology, Laiko General Hospital, Athens, Greece.
Division of Cardiology, Murska Sobota, Murska Sobota and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Eur J Heart Fail. 2019 Nov;21(11):1383-1397. doi: 10.1002/ejhf.1532. Epub 2019 Jun 18.
To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM-HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes.
Outpatients with HFrEF in the ESC-EORP-HFA Long-Term Heart Failure (HF-LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM-HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM-HF and guideline criteria, respectively. Absent PARADIGM-HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub-optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub-optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM-HF and guidelines. One-year heart failure hospitalization was higher (12% and 17% vs. 12%) and all-cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM-HF.
Among outpatients with HFrEF in the ESC-EORP-HFA HF-LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM-HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM-HF enalapril group.
评估根据欧洲药品管理局/食品和药物管理局（EMA/FDA）标签、PARADIGM-HF 试验和 2016 ESC 指南，符合沙库巴曲缬沙坦（LCZ696）适应证的射血分数降低的心力衰竭（HFrEF）患者比例，以及适应证与结局之间的关系。
纳入 2011 年 3 月至 2013 年 11 月 ESC-EORP-HFA 长期心力衰竭（HF-LT）注册研究中的门诊 HFrEF 患者。应用 EMA/FDA 标签、PARADIGM-HF 和 ESC 指南的 LCZ696 适应证标准。在 5443 例患者中，2197 例和 2373 例有完整的试验和指南适应证评估信息，分别有 84%、12%和 12%符合 EMA/FDA 标签、PARADIGM-HF 和指南标准。不符合 PARADIGM-HF 标准的为低利钠肽（21%）、高钾血症（4%）、低血压（7%）和亚最佳药物治疗（74%）；不符合指南标准的为 LVEF>35%（23%）、利钠肽水平不足（30%）和亚最佳药物治疗（82%）；不符合标签标准的为无症状（纽约心脏协会心功能分级 I 级）。当每天需要 ACEi/ARB ≥10mg 依那普利（而非 ≥20mg）时，根据 PARADIGM-HF 和指南标准，适应证从 12%上升至 28%。与 PARADIGM-HF 依那普利组相比，符合注册标准的患者 1 年心力衰竭住院率更高（12%和 17% vs. 12%），全因死亡率更低（5.3%和 6.5% vs. 7.7%）。
在 ESC-EORP-HFA HF-LT 注册研究的门诊 HFrEF 患者中，84%符合标签标准，而如果分别需要≥20mg 和≥10mg 依那普利，符合 LCZ696 的 PARADIGM-HF 和指南标准的患者比例仅为 12%和 28%。符合 LCZ696 适应证的注册患者心力衰竭住院率更高，但死亡率低于 PARADIGM-HF 依那普利组。
