Division of General Internal Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, Canada.
Service de Médecine Intensive-Réanimation, Centre Hospitalier Universitaire d'Angers, Angers, France.
Clin Infect Dis. 2024 Sep 26;79(3):615-625. doi: 10.1093/cid/ciae306.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) down-regulates angiotensin-converting enzyme 2, potentially increasing angiotensin II. We hypothesized that losartan compared to usual care decreases mortality and is safe in patients hospitalized with coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of losartan versus usual care on 28-day mortality in patients hospitalized for acute COVID-19.
Eligibility criteria included adults admitted for acute COVID-19. Exclusion criteria were hypotension, hyperkalemia, acute kidney injury, and use of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors within 7 days. Participants were randomized to losartan 25-100 mg/day orally for the hospital duration or 3 months or the control arm (usual care) in 29 hospitals in Canada and France. The primary outcome was 28-day mortality. Secondary outcomes were hospital mortality, organ support, and serious adverse events (SAEs).
The trial was stopped early because of a serious safety concern with losartan. In 341 patients, any SAE and hypotension were significantly higher in the losartan versus usual care groups (any SAE: 39.8% vs 27.2%, respectively, P = .01; hypotension: 30.4% vs 15.3%, respectively, P < .001) in both ward and intensive care patients. The 28-day mortality did not differ between losartan (6.5%) versus usual care (5.9%) (odds ratio, 1.11 [95% confidence interval, .47-2.64]; P = .81), nor did organ dysfunction or secondary outcomes.
Caution is needed in deciding which patients to start or continue using ARBs in patients hospitalized with pneumonia to mitigate risk of hypotension, acute kidney injury, and other side effects. ARBs should not be added to care of patients hospitalized for acute COVID-19.
NCT04606563.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）下调血管紧张素转换酶 2，可能会增加血管紧张素 II。我们假设与常规治疗相比，氯沙坦可降低冠状病毒病 2019（COVID-19）住院患者的死亡率，并安全有效。我们旨在评估氯沙坦与常规治疗对因急性 COVID-19 住院患者 28 天死亡率的影响。
纳入标准包括因急性 COVID-19 入院的成年人。排除标准为低血压、高钾血症、急性肾损伤以及在 7 天内使用血管紧张素受体阻滞剂（ARBs）或血管紧张素转换酶抑制剂。在加拿大和法国的 29 家医院中，将参与者随机分配到氯沙坦 25-100mg/天口服治疗住院期间或 3 个月或对照组（常规治疗）。主要结局是 28 天死亡率。次要结局是住院死亡率、器官支持和严重不良事件（SAEs）。
由于氯沙坦的严重安全问题，试验提前停止。在 341 例患者中，氯沙坦组与常规治疗组的任何 SAE 和低血压发生率均显著升高（任何 SAE：分别为 39.8%和 27.2%，P=0.01；低血压：分别为 30.4%和 15.3%，均 P<0.001），包括病房和重症监护患者。氯沙坦组（6.5%）与常规治疗组（5.9%）的 28 天死亡率无差异（比值比，1.11[95%置信区间，0.47-2.64]；P=0.81），器官功能障碍或次要结局也无差异。
在决定对因肺炎住院的患者开始或继续使用 ARB 以降低低血压、急性肾损伤和其他副作用的风险时，应谨慎。ARBs 不应添加到急性 COVID-19 住院患者的治疗中。
NCT04606563。
