Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.
Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.
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DOI：
10.1016/s2213-2600(21)00214-9
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发表时间：
2021-08
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通讯作者：
ACEI-COVID investigators
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作者：
Bauer A;Schreinlechner M;Sappler N;Dolejsi T;Tilg H;Aulinger BA;Weiss G;Bellmann-Weiler R;Adolf C;Wolf D;Pirklbauer M;Graziadei I;Gänzer H;von Bary C;May AE;Wöll E;von Scheidt W;Rassaf T;Duerschmied D;Brenner C;Kääb S;Metzler B;Joannidis M;Kain HU;Kaiser N;Schwinger R;Witzenbichler B;Alber H;Straube F;Hartmann N;Achenbach S;von Bergwelt-Baildon M;von Stülpnagel L;Schoenherr S;Forer L;Embacher-Aichhorn S;Mansmann U;Rizas KD;Massberg S;ACEI-COVID investigators
SARS-CoV-2进入人类细胞依赖于血管紧张素转换酶2，肾素-血管紧张素系统(RAS)的抑制剂可以上调该酶的表达。我们的目标是验证我们的假设，即停止使用血管紧张素转换酶抑制剂(ACEI)或血管紧张素II受体阻滞剂(ARB)的慢性治疗可以缓解新近发病的新冠肺炎的病程。ACEI-COVID是一个平行小组，在奥地利和德国的35个中心进行了随机、对照、开放标签试验。年龄在18岁及以上的患者，如果他们最近出现SARS-CoV-2感染的症状，并接受了ACEI或ARB的长期治疗，则纳入研究。患者被随机分配为1：1停止或继续应用RAS抑制30d。主要结果是30天内的最大序贯器官衰竭评估(SOFA)评分，其中死亡与最大可达到的SOFA评分一起评分。次要终点是死亡调整SOFA评分(AUCSOFA)以下的面积、平均SOFA评分、住进重症监护病房、机械通气和死亡。分析是在修改的意向治疗的基础上进行的。这项试验在ClinicalTrials.gov注册，NCT04353596。在2020年4月20日至2021年1月20日期间，204名患者(平均年龄75岁[IQR 66-80]，其中37%为女性)被随机分为停止(n=104)或继续(n=100)RAS抑制。30天内，停药组104例中有8例(8%)死亡，继续组100例中有12例(12%)死亡(p=0.42)。中位数[IQR]最大SOFA评分为0·00(0·00-2·00)比1·00(0·00-3·00)(P=0·12)。停止服药与AUCSOFA显著降低(0·00[0·00-9·25]vs 3·50[0·00-23·50]；p=0·040)、平均SOFA评分(0·00[0·00-0·31]vs 0·12[0·00-0·78]；p=0·040)和30天SOFA评分(0·00[10-90百分位数，0·00-1·20]vs 0·00[0·00-24·00]；p=0·023)。30天后，停药组11例(11%)和继续组23例(23%)出现器官功能障碍(SOFA评分≥1)或死亡(P=0.017)。在机械通气量(10%比8%，P=0·87)和住进重症监护病房(20[19%]比18[18%]，P=0·96)方面，停用组和继续组之间差异无统计学意义。停止RAS抑制对新冠肺炎的最严重程度无明显影响，但可能导致更快和更好的恢复。继续或停止治疗的决定应在个人基础上做出，考虑到风险概况、RAS抑制的适应症以及替代疗法和门诊监测选项的可用性。奥地利科学基金会和德国心血管研究中心。
SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin–angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19. ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUCSOFA), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596. Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66–80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00–2·00) vs 1·00 (0·00–3·00); p=0·12). Discontinuation was associated with a significantly lower AUCSOFA (0·00 [0·00–9·25] vs 3·50 [0·00–23·50]; p=0·040), mean SOFA score (0·00 [0·00–0·31] vs 0·12 [0·00–0·78]; p=0·040), and 30-day SOFA score (0·00 [10–90th percentile, 0·00–1·20] vs 0·00 [0·00–24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group. Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options. Austrian Science Fund and German Center for Cardiovascular Research.