Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain.
Department of Biomedical Sciences (Pharmacology Section), University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain.
BMC Med. 2021 May 12;19(1):118. doi: 10.1186/s12916-021-01992-9.
In the first wave of the COVID-19 pandemic, the hypothesis that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) increased the risk and/or severity of the disease was widely spread. Consequently, in many hospitals, these drugs were discontinued as a "precautionary measure". We aimed to assess whether the in-hospital discontinuation of ARBs or ACEIs, in real-life conditions, was associated with a reduced risk of death as compared to their continuation and also to compare head-to-head the continuation of ARBs with the continuation of ACEIs.
Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs), and their 95%CIs were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators.
Out of 625 ACEI/ARB users, 340 (54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI 0.70-1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%, N=125) as compared to those who continued with ACEIs (33.1%, N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI 0.29-0.93), being especially notorious among males (HR=0.34; 95%CI 0.12-0.93), subjects older than 74 years (HR=0.46; 95%CI 0.25-0.85), and patients with obesity (HR=0.22; 95%CI 0.05-0.94), diabetes (HR=0.36; 95%CI 0.13-0.97), and heart failure (HR=0.12; 95%CI 0.03-0.97).
The discontinuation of ACEIs/ARBs at admission did not improve the in-hospital survival. On the contrary, the continuation with ARBs was associated with a trend to a reduced mortality as compared to their discontinuation and to a significantly lower mortality risk as compared to the continuation with ACEIs, particularly in high-risk patients.
在 COVID-19 大流行的第一波中,血管紧张素受体阻滞剂 (ARB) 和血管紧张素转换酶抑制剂 (ACEI) 增加疾病风险和/或严重程度的假说广为流传。因此,在许多医院,这些药物被停用作为“预防措施”。我们旨在评估在真实情况下停用 ARB 或 ACEI 是否与降低死亡风险相关,以及比较 ARB 的继续使用与 ACEI 的继续使用。
从西班牙马德里的 7 家医院连续选择 2020 年 3 月期间因 PCR 确诊 COVID-19 需要住院的成年患者。其中,我们确定了 ACEI/ARB 的门诊使用者,并根据入院时的治疗停药/继续分为两组。然后,他们一直随访至出院或院内死亡。进行意向治疗生存分析,并通过 Cox 回归模型计算风险比 (HR) 和 95%CI,该模型通过停药的倾向评分进行调整,并通过潜在中介物进行控制。
在 625 名 ACEI/ARB 使用者中,有 340 名(54.4%)停止了治疗。停药组和继续治疗组的院内死亡率分别为 27.6%和 27.7%(HR=1.01;95%CI 0.70-1.46)。ARB 和 ACEI 停药之间没有观察到死亡率差异(分别为 28.6%和 27.1%),而继续使用 ARB 的患者死亡率明显低于继续使用 ACEI 的患者(分别为 20.8%,N=125 和 33.1%,N=136;p=0.03)。ARB 与 ACEI 继续治疗的头对头比较(ARB 与 ACEI 继续治疗的头对头比较)得出调整后的 HR 为 0.52(95%CI 0.29-0.93),在男性(HR=0.34;95%CI 0.12-0.93)、年龄大于 74 岁(HR=0.46;95%CI 0.25-0.85)和肥胖(HR=0.22;95%CI 0.05-0.94)、糖尿病(HR=0.36;95%CI 0.13-0.97)和心力衰竭(HR=0.12;95%CI 0.03-0.97)患者中尤其明显。
入院时停止使用 ACEI/ARB 并未改善院内生存率。相反,与停药相比,继续使用 ARB 与死亡率降低趋势相关,与继续使用 ACEI 相比,死亡率显著降低,特别是在高危患者中。