Impact of in-hospital discontinuation with angiotensin receptor blockers or converting enzyme inhibitors on mortality of COVID-19 patients: a retrospective cohort study

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

Insights into the association of ACEIs/ARBs use and COVID-19 prognosis: a multistate modelling study of nationwide hospital surveillance data from Belgium

“…Among 397 patients with COVID-19 admitted to hospitals in Rozzano-Milan (Italy), the risk of mortality was significantly reduced in patients who continued ACEIs/ARBs as compared with those who discontinued and those not taking ACEIs/ARBs therapy (OR 0.14, 95% CI 0.03 to 0.66) 47. Using data from seven hospitals in Madrid (Spain), no difference in mortality rates was observed among patients that discontinued (340 patients) ACEIs/ARBs treatment (HR 1.01, 95% CI 0.70 to 1.46) versus those that continued (280 patients) 48. Furthermore, recent data from two randomised trials could not confirm any impact on clinical outcomes in hospitalised patients with COVID-19 discontinuing treatment of ACEIs or ARBs as compared with those continuing their treatment,49 50 hereby further supporting a safe ACEIs/ARBs treatment continuation if there is an indication for treatment.…”

The effect of renin–angiotensin–aldosterone system inhibitors in patients with hypertension and COVID-19: A meta-analysis of randomized controlled trials and propensity score-matched studies

“…Fifty-five studies were excluded according to our criteria upon reading the full text of the articles. Ultimately, we included 17 studies [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] comprising 30,416 patients with hypertension and COVID-19 in our meta-analysis. The basic characteristics of the included studies are summarized in Table 1 .…”

Exposure to sulfur mustard increases the risk for mortality in patients with COVID-19 infection: A cohort study

“…Researchers studying COVID-19 proposed a possible role for ACE in the pathogenesis of the infection. Hypoxia-induced increase in ACE2 expression in type II AEC, angiotensin II receptor blockers, and ACE inhibitors are believed to affect the course of acute respiratory distress syndrome and the risk for mortality in COVID-19 [ [34] , [35] , [36] ].…”