在血管扩张性休克中以较低的升压药剂量起始血管紧张素 II：ATHOS-3 临床试验的探索性事后分析。
Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial.
机构信息
Departments of Pharmacy and Anesthesiology, Mayo Clinic, Rochester, MN, USA.
Department of Critical Care, Melbourne Medical School, University of Melbourne, Parkville, Australia.
出版信息
Crit Care. 2023 May 5;27(1):175. doi: 10.1186/s13054-023-04446-1.
BACKGROUND
High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II).
METHODS
Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation.
RESULTS
Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups.
CONCLUSIONS
This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial.
TRIAL REGISTRATION
The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.
背景
大剂量血管加压药预示着血管扩张性休克的预后不良。我们旨在评估在接受血管紧张素 II（AT II）治疗的患者中，基线血管加压药剂量对结局的影响。
方法
对血管扩张性休克患者接受血管紧张素 II 治疗的高输出休克（ATHOS-3）试验数据进行探索性事后分析。ATHOS-3 试验将 321 名接受血管扩张性休克治疗的患者随机分为两组，尽管接受了标准的去甲肾上腺素等效剂量（NED）> 0.2 µg/kg/min 的血管加压剂支持，但仍处于低血压（平均动脉压为 55-70 mmHg），一组接受 AT II 治疗，另一组接受安慰剂治疗，两组均在标准的血管加压剂治疗基础上加用 AT II 或安慰剂。在研究药物开始时，患者根据基础 NED 分为低剂量（≤ 0.25 µg/kg/min；n = 104）或高剂量（> 0.25 µg/kg/min；n = 217）组。主要结局是在研究药物开始时基线 NED≤0.25 µg/kg/min 的患者中，AT II 组与安慰剂组在 28 天生存率上的差异。
结果
在 321 名患者中，低 NED 亚组中 AT II（n = 56）和安慰剂（n = 48）组的中位基线 NED 相似（每支手臂的中位数分别为 0.21 µg/kg/min，p = 0.45）。在高 NED 亚组中，基线 NED 中位数也相似（AT II 组 0.47 µg/kg/min，n = 107 与安慰剂组 0.45 µg/kg/min，n = 110，p = 0.75）。在校正严重程度后，与安慰剂相比，低 NED 亚组中接受 AT II 治疗的患者在 28 天内死亡的可能性减半（HR 0.509；95% CI 0.274-0.945，p = 0.03）。在高 NED 亚组中，AT II 组与安慰剂组在 28 天生存率上无差异（HR 0.933；95% CI 0.644-1.350，p = 0.71）。低 NED AT II 亚组的严重不良事件发生率低于低 NED 安慰剂亚组，但差异无统计学意义，且在高 NED 亚组中相似。
结论
这项对 3 期临床试验数据的探索性事后分析表明，在接受其他血管加压剂治疗时，较低剂量的 AT II 可能具有潜在的益处。这些数据可能为前瞻性试验的设计提供信息。
试验注册
ATHOS-3 试验在 clinicaltrials.gov 注册库中注册（注册号：NCT02338843）。2015 年 1 月 14 日注册。
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