Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.
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DOI：
10.1016/s2213-2600(20)30558-0
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Chirinos JA
中科院分区：
文献类型：
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作者：
Cohen JB;Hanff TC;William P;Sweitzer N;Rosado-Santander NR;Medina C;Rodriguez-Mori JE;Renna N;Chang TI;Corrales-Medina V;Andrade-Villanueva JF;Barbagelata A;Cristodulo-Cortez R;Díaz-Cucho OA;Spaak J;Alfonso CE;Valdivia-Vega R;Villavicencio-Carranza M;Ayala-García RJ;Castro-Callirgos CA;González-Hernández LA;Bernales-Salas EF;Coacalla-Guerra JC;Salinas-Herrera CD;Nicolosi L;Basconcel M;Byrd JB;Sharkoski T;Bendezú-Huasasquiche LE;Chittams J;Edmonston DL;Vasquez CR;Chirinos JA
从生物学角度考虑，肾素-血管紧张素系统抑制剂可能会影响COVID-19的严重程度。我们的目的是评估持续或停止使用肾素-血管紧张素系统抑制剂（血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂）是否会影响COVID-19住院患者的预后。REPLACE COVID试验是一项前瞻性、随机、开放标签试验，在全球7个国家的20家大型转诊医院进行。符合条件的参与者年龄在18岁及以上，因COVID-19入院，入院前接受肾素-血管紧张素系统抑制剂治疗。排除有继续或停止肾素-血管紧张素系统抑制剂治疗禁忌症的个体。参与者被随机分配（1:1）继续或停止他们的肾素-血管紧张素系统抑制剂使用排列块随机化，分配隐藏使用安全的基于网络的随机化系统。主要结局是全球排名得分，其中参与者分为四个等级，包括死亡时间、机械通气持续时间、肾脏替代或血管加压治疗时间以及住院期间的多器官功能障碍。在意向治疗人群中进行了初步分析。REPLACE COVID试验已在ClinicalTrials.gov注册，注册号为NCT04338009。在2020年3月31日至8月20日期间，152名参与者被纳入研究，随机分配继续或停止肾素-血管紧张素系统抑制剂治疗（继续组n=75；停止组n=77）。参与者的平均年龄为62岁（SD 12）， 68名（45%）为女性，平均体重指数为33 kg/m2 (SD 8)， 79名（52%）患有糖尿病。与停用肾素-血管紧张素系统抑制剂相比，继续治疗对全局评分没有影响（继续治疗的中位评分为73 [IQR 40-110]，而停用治疗的中位评分为81 [38-117]；β系数为8 [95% CI−13至29]）。75名继续组患者中有16人（21%）死亡，77名中止组患者中有14人（18%）死亡，75名继续组患者中有11人（15%）死亡，77名中止组患者中有10人（13%）死亡。继续组29例（39%）和停药组28例（36%）至少发生一次不良事件（χ2治疗组间不良事件检验p= 0.77）。在随访期间，两组患者的血压、血钾或肌酐均无差异。根据国际社会的建议，肾素-血管紧张素系统抑制剂可在COVID-19住院患者中安全地继续使用。REPLACE COVID调查员，REPLACE COVID试验社会筹款活动和FastGrants。
Biological considerations suggest that renin–angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin–angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin–angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin–angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin–angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin–angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin–angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40–110] for continuation vs 81 [38–117] for discontinuation; β-coefficient 8 [95% CI −13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. Consistent with international society recommendations, renin–angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.