HFrEF 初始诊断后四联疗法启用时间
该回顾性队列研究纳入 2020–2023 年美国退伍军人中 52 850 例新发 HFrEF 患者，中位随访 2.9 年。结果显示仅 21.2% 患者达到四联 GDMT，中位启用时间为 197 天。药物共付额是影响四联疗法达成的可干预障碍。
要点
- HFrEF 四联疗法达成率低，仅 21.2%，中位启用时间 197 天。
- 非白人种族与无处方共付额者四联疗法达成率更高。
- 处方共付额是可干预障碍，可作为提升四联疗法及时性的干预目标。
核心结论
- 仅 21.2% 的 HFrEF 患者在中位随访 2.9 年内达到四联疗法，中位启用时间为 6 个月。
- 药物共付额是可干预的障碍，可作为改善四联疗法及时性的干预目标。
研究设计与样本
- 纳入 52 850 例新发 HFrEF 患者，中位年龄 71.8 岁，97% 为男性。
主要发现
- 11 217 例（21.2%）在中位随访 2.9 年期间达到四联疗法，中位启用时间 197 天。
- 校正后，黑人患者 HR 1.22（95%CI 1.15–1.30）、西班牙裔患者 HR 1.21（95%CI 1.09–1.33）、其他种族患者 HR 1.11（95%CI 1.02–1.20），均高于白人患者。
- 女性与男性四联疗法达成率无差异，HR 0.97（95%CI 0.86–1.09）。
- 有处方共付额患者四联疗法达成率比无处方共付额患者低 8%，HR 0.92（95%CI 0.87–0.96）。
- 门诊诊断患者四联疗法达成率为 22.2%，高于住院诊断患者的 14.2%；合并糖尿病者为 23.6%，高于无糖尿病者的 19.3%；无慢性肾病者为 22.5%，高于合并慢性肾病者的 18.1%。
关键数值与推荐
- 四联疗法定义为药房配药记录中 β 受体阻滞剂、肾素-血管紧张素系统抑制剂、盐皮质激素受体拮抗剂和 SGLT2 抑制剂四类药物同时使用。
- 启用时间定义为四类药物首次出现重叠的日期，基于发药日期和供应天数计算。
临床怎么用
- 对 HFrEF 患者应尽早启动并优化四联 GDMT，避免延迟至半年以上。
- 临床可重点关注有药物共付负担、住院诊断、无糖尿病或合并慢性肾病的患者，因其四联疗法达成率较低。
局限性
- 研究人群以美国退伍军人男性为主，结果外推至其他人群需谨慎。
- 四联疗法依据药房配药记录判定，可能无法完全反映实际服药情况。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
IMPORTANCE: Timely prescription of quadruple guideline-directed medical therapies (GDMTs) for patients with heart failure with reduced ejection fraction (HFrEF) is associated with improved morbidity and mortality, yet contemporary estimates of time to quadruple therapy (TTQ) and the factors associated with its achievement remain unknown. OBJECTIVE: To characterize TTQ and factors associated with TTQ in HFrEF. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study including patients with incident HFrEF from the Veterans Health Administration database during the January 1, 2020, to December 31, 2023, period. Study data were analyzed from November 2024 to December 2025. EXPOSURES: Primary factors included race and ethnicity, sex, and copay status (priority group). Secondary factors included clinical characteristics. MAIN OUTCOMES AND MEASURES: The main outcome included quadruple therapy according to pharmacy fill data-concurrent use of evidence-based β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors. TTQ was defined as the first date that all 4 medication classes overlapped, based on dispense date and days' supply. RESULTS: Among 52 850 patients with incident HFrEF (median [SD] age, 71.8 [11] years; 51 473 male [97%]; 10 791 Black [20%]; 2528 Hispanic [5%]; 35 867 White [68%]; 3664 other [7%]), 11 217 (21.2%) achieved quadruple therapy over a median (IQR) follow-up of 2.9 (1.9-3.9) years. The median (IQR) TTQ was 197 (49-528) days. After adjustment, Black patients (hazard ratio [HR], 1.22; 95% CI, 1.15-1.30), Hispanic patients (HR, 1.21; 95% CI, 1.09-1.33), and those from other racial or ethnic groups (HR, 1.11; 95% CI, 1.02-1.20) had higher rates of quadruple therapy than White patients. There was no difference in TTQ in females vs males (HR, 0.97; 95% CI, 0.86-1.09). Prescription copays (priority groups 2-8) were associated with an 8% lower rate of achieving quadruple therapy (HR, 0.92; 95% CI, 0.87-0.96) than no prescription copay (priority group 1). Rates of quadruple therapy were higher among veterans with an outpatient HFrEF diagnosis vs inpatient (22.2% vs 14.2%), with diabetes vs without diabetes (23.6% vs 19.3%), and without chronic kidney disease vs with chronic kidney disease (22.5% vs 18.1%). CONCLUSION AND RELEVANCE: Results of this cohort study suggest that opportunities exist to improve both the rate and timeliness of quadruple therapy as only 21.2% of patients with HFrEF achieved it, with a median follow-up of 2.9 years and TTQ of 6 months. Medication copays represent a modifiable barrier, providing a potential target for interventions to enhance TTQ.
引用
- Jacobs, Greene, Vanneman, et al. Time to Quadruple Therapy After Initial Diagnosis of Heart Failure With Reduced Ejection Fraction. JAMA Cardiol. 2026. PMID: 41920552. doi:10.1001/jamacardio.2026.0375
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。