Background

There is a paucity of evidence for dose and pace of up-titration of guideline-directed medical therapies after admission to hospital for acute heart failure.

Methods

In this multinational, open-label, randomised, parallel-group trial (STRONG-HF), patients aged 18–85 years admitted to hospital with acute heart failure, not treated with full doses of guideline-directed drug treatment, were recruited from 87 hospitals in 14 countries. Before discharge, eligible patients were randomly assigned (1:1), stratified by left ventricular ejection fraction (≤40% vs >40%) and country, with blocks of size 30 within strata and randomly ordered sub-blocks of 2, 4, and 6, to either usual care or high-intensity care. Usual care followed usual local practice, and high-intensity care involved the up-titration of treatments to 100% of recommended doses within 2 weeks of discharge and four scheduled outpatient visits over the 2 months after discharge that closely monitored clinical status, laboratory values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. The primary endpoint was 180-day readmission to hospital due to heart failure or all-cause death. Efficacy and safety were assessed in the intention-to-treat (ITT) population (ie, all patients validly randomly assigned to treatment). The primary endpoint was assessed in all patients enrolled at hospitals that followed up patients to day 180. Because of a protocol amendment to the primary endpoint, the results of patients enrolled on or before this amendment were down-weighted. This study is registered with ClinicalTrials.gov, NCT03412201, and is now complete.

Findings

Between May 10, 2018, and Sept 23, 2022, 1641 patients were screened and 1078 were successfully randomly assigned to high-intensity care (n=542) or usual care (n=536; ITT population). Mean age was 63·0 years (SD 13·6), 416 (39%) of 1078 patients were female, 662 (61%) were male, 832 (77%) were White or Caucasian, 230 (21%) were Black, 12 (1%) were other races, one (<1%) was Native American, and one (<1%) was Pacific Islander (two [<1%] had missing data on race). The study was stopped early per the data and safety monitoring board's recommendation because of greater than expected between-group differences. As of data cutoff (Oct 13, 2022), by day 90, a higher proportion of patients in the high-intensity care group had been up-titrated to full doses of prescribed drugs (renin-angiotensin blockers 278 [55%] of 505 vs 11 [2%] of 497; β blockers 249 [49%] vs 20 [4%]; and mineralocorticoid receptor antagonists 423 [84%] vs 231 [46%]). By day 90, blood pressure, pulse, New York Heart Association class, bodyweight, and NT-proBNP concentration had decreased more in the high-intensity care group than in the usual care group. Heart failure readmission or all-cause death up to day 180 occurred in 74 (15·2% down-weighted adjusted Kaplan-Meier estimate) of 506 patients in the high-intensity care group and 109 (23·3%) of 502 patients in the usual care group (adjusted risk difference 8·1% [95% CI 2·9–13·2]; p=0·0021; risk ratio 0·66 [95% CI 0·50–0·86]). More adverse events by 90 days occurred in the high-intensity care group (223 [41%] of 542) than in the usual care group (158 [29%] of 536) but similar incidences of serious adverse events (88 [16%] vs 92 [17%]) and fatal adverse events (25 [5%] vs 32 [6%]) were reported in each group.

Interpretation

An intensive treatment strategy of rapid up-titration of guideline-directed medication and close follow-up after an acute heart failure admission was readily accepted by patients because it reduced symptoms, improved quality of life, and reduced the risk of 180-day all-cause death or heart failure readmission compared with usual care.

Funding

Roche Diagnostics.

中文翻译：

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急性心力衰竭指南指导药物治疗（STRONG-HF）的安全性、耐受性和有效性：一项多国、开放标签、随机试验

背景

因急性心力衰竭入院后，指南指导的药物治疗剂量和滴定速度的证据很少。

方法

在这项多国、开放标签、随机、平行组试验 (STRONG-HF) 中，招募了 87 名年龄在 18-85 岁之间、因急性心力衰竭入院且未接受全剂量指南指导药物治疗的患者。 14 个国家的医院。出院前，符合条件的患者被随机分配（1:1），按左心室射血分数（≤40% vs >40%）和国家进行分层，层内的块大小为 30，随机排序的子块为 2、4、 6、常规护理或高强度护理。常规护理遵循当地惯例，高强度护理包括在出院后 2 周内将治疗滴定至推荐剂量的 100%，并在出院后 2 个月内安排 4 次门诊就诊，密切监测临床状态、实验室值、和 N 末端 B 型利钠肽原 (NT-proBNP) 浓度。主要终点是 180 天因心力衰竭或全因死亡再次入院。在意向治疗（ITT）人群（即所有有效随机分配接受治疗的患者）中评估疗效和安全性。对在随访患者至第 180 天的医院入组的所有患者进行主要终点评估。由于对主要终点的方案修订，在此次修订时或之前入组的患者的结果被降低了权重。这项研究已在 ClinicalTrials.gov 注册，NCT03412201，现已完成。

发现

2018年5月10日至2022年9月23日期间，对1641名患者进行了筛查，其中1078名患者成功随机分配至高强度护理组（n=542）或常规护理组（n=536；ITT人群）。平均年龄为 63·0 岁 (SD 13·6)，1078 名患者中 416 名 (39%) 为女性，662 名 (61%) 为男性，832 名 (77%) 为白人或白种人，230 名 (21%) 为黑人，12 名 (1%) 是其他种族，1 名 (<1%) 是美洲原住民，1 名 (<1%) 是太平洋岛民（两名 [<1%] 缺少种族数据）。由于组间差异大于预期，根据数据和安全监测委员会的建议，该研究提前停止。截至数据截止（2022 年 10 月 13 日），到第 90 天，高强度护理组中较高比例的患者已增量至全剂量处方药物（肾素血管紧张素阻滞剂 278 [55%] of 505 497 例中11 例 [2%]；β 受体阻滞剂 249 例 [49%] 例对比20 例 [4%]；盐皮质激素受体拮抗剂 423 例 [84%] 例对比231 例 [46%]。到第 90 天，高强度护理组的血压、脉搏、纽约心脏协会分级、体重和 NT-proBNP 浓度比常规护理组下降更多。高强度护理组中 506 名患者中的 74 名（15·2% 降权调整 Kaplan-Meier 估计）和 502 名患者中的 109 名（23·3%）发生心力衰竭再入院或直至第 180 天的全因死亡常规护理组（调整后风险差异 8·1% [95% CI 2·9–13·2]；p=0·0021；风险比 0·66 [95% CI 0·50–0·86]） 。到 90 天时，高强度护理组（542 例中的 223 例 [41%]）发生的不良事件多于常规护理组（536 例中的 158 例 [29%]），但严重不良事件的发生率相似（88 例 [16%]） ] vs 92 [17%]）和致命不良事件（25 [5%] vs 32 [6%]）每组均报告。

解释

急性心力衰竭入院后快速增加指南指导用药并密切随访的强化治疗策略很容易被患者接受，因为它减轻了症状，提高了生活质量，并降低了 180 天全心衰竭的风险。与常规护理相比，会导致死亡或心力衰竭再入院。

资金

罗氏诊断。