Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection

Abstract

BackgroundData regarding the benefits or harm associated with the continuation of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), especially the effect on inflammation, in patients who are hypertensive and hospitalized with coronavirus disease 2019 (COVID-19) in the United States are unclear.MethodsThis is a single-center cohort study of patients sequentially hospitalized with COVID-19 at Stony Brook University Medical Center from March 7, 2020 to April 1, 2020, inclusive of these dates. Data collection included history of known comorbidities, medications, vital signs, and laboratory values (at admission and during the hospitalization). Outcomes include inflammatory burden (composite scores for multiple markers of inflammation), AKI, admission to the intensive care unit (ICU), need for invasive mechanical ventilation, and mortality.ResultsOf the 300 patients in the study cohort, 80 patients (27%) had history of ACEI or ARB use before admission, with 61% (49/80) of these patients continuing the medications during hospitalization. Multivariable analysis revealed that the history of ACEI or ARB use before hospitalization was not associated with worse outcomes. In addition, the continuation of these agents during hospitalization was not associated with an increase in adverse outcomes and predicted fewer ICU admissions (odds ratio, 0.25; 95% CI, 0.08 to 0.81) with a decrease in the severity of inflammatory burden (peak C-reactive protein, 6.9±3.1 mg/dl, P=0.03; peak inflammation score, 2.3±1.1 unit reduction, P=0.04).ConclusionsUse of ACEI or ARBs before hospitalization was not associated with adverse outcomes in COVID-19, and the therapeutic benefits of continuing ACEI or ARB in patients hospitalized with COVID-19 was not offset by adverse outcomes.

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

“…The comparison of mortality and clinical severity outcomes between ACEI/ARB users and non-ACEI/ARB users with COVID-19 is summarized in Table 2 . There were 50 studies [ 35 – 38 , 41 – 45 , 48 – 51 , 53 – 59 , 61 , 62 , 64 – 82 , 85 – 93 ] and 36 studies [ 35 , 36 , 39 – 41 , 43 – 53 , 55 , 56 , 59 – 63 , 66 , 71 , 74 , 75 , 78 , 80 , 83 – 85 , 89 – 92 ], respectively, that reported mortality outcomes and clinical severity outcomes among COVID-19 patients with and without the use of ACEIs/ARBs. Among 50 studies that reported mortality outcomes, 24 studies [ 35 , 36 , 54 , 56 , 57 , 59 , 64 , 66 , 67 , 69 , 70 , 72 , 74 – 78 , 80 , 81 , 86 , 88 , 89 , 92 , 93 ] provided adjusted mortality estimates with the use of an ACEI/ARB relative to the non-use of an ACEI/ARB.…”

“… ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, CI confidence interval, COVID - 19 coronavirus disease 2019, HR hazard ratio, N/A not available, OR odds ratio a The definition of severe/critical disease in the studies by Amaouche et al [ 35 ], Feng et al [ 39 ], Feng et al [ 40 ], Gao et al [ 41 ], Hu et al [ 43 ], Huang et al [ 44 ], Li et al [ 45 ], Li et al [ 46 ], Liu et al [ 47 ], Meng et al [ 48 ], Peng et al [ 49 ], Yan et al [ 52 ], and Yang et al [ 53 ] is based on the definition given in ‘Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia’ by Chinese National Health Commission; Chen et al [ 36 ] is based on the development of multiple organ dysfunction syndrome; Tan et al [ 50 ] is based on the development of acute respiratory distress syndrome; Xu et al [ 51 ], Fosbøl et al [ 59 ], Dauchet et al [ 60 ], Liabeuf et al [ 61 ], Zhou et al [ 63 ], Felice et al [ 66 ], Sardu et al [ 71 ], Dalan et al [ 74 ], Son et al [ 78 ], López-Otero et al [ 80 ], Argenziano et al [ 83 ], Chaudhri et al [ 85 ], Lam et al [ 89 ], Mehta et al [ 90 ], Richardson et al [ 91 ], and Shah et al [ 92 ] are based on the requirement for admission into intensive care units; Zeng et al [ 55 ] is based on the guideline for community-acquired pneumonia; Zhang et al [ 56 ] is based on the development of septic shock; Oussalah et al [ 62 ] is based on the requirement for intubation or mechanical ventilation; Choi et al [ 75 ] is based on the requirement for mechanical ventilation, admission into intensive care units, continuous renal replacement therapy, or extracorporeal membrane oxygenation; and Chang et al [ 84 ] is based on the requirement for admission into intensive care units or intubation b Preprint …”

“…An in-depth analysis of study methods and findings for each original study is of utmost importance to prevent false assumptions about the safety of RAS inhibitors in COVID-19. From our literature review, there have been a large number of observational studies [ 35 – 38 , 41 – 45 , 48 – 51 , 53 – 59 , 61 , 62 , 64 – 82 , 85 – 93 ] thus far evaluating the association between the use of ACEIs/ARBs in COVID-19 and mortality since concerns were raised with regard to the potential harms from the use of these drugs. However, conflicting results were observed among these studies.…”

“…However, conflicting results were observed among these studies. There were 23 studies [ 37 , 41 – 43 , 49 , 59 , 61 , 62 , 65 , 68 , 71 , 73 , 76 – 81 , 85 , 88 , 90 – 92 ] that reported a higher crude mortality rate; conversely 19 studies [ 36 , 38 , 44 , 45 , 48 , 50 , 51 , 53 – 56 , 58 , 64 , 66 , 75 , 82 , 87 , 89 , 93 ] reported a lower crude mortality rate among ACEI/ARB users with COVID-19 compared with their counterparts without receiving ACEIs/ARBs. However, as mentioned earlier, there were only a few studies that adjusted covariates that may confound the association between the use of ACEIs/ARBs in COVID-19 and the risk of mortality.…”

“…The characteristics of the shortlisted studies are summarized in Table 1. Among shortlisted studies, 23 studies were from China , nine studies were from Italy [64][65][66][67][68][69][70][71][72], ten studies were from the United States [83][84][85][86][87][88][89][90][91][92], four studies were from South Korea [75][76][77][78], three studies were from France [60][61][62], two studies were from Spain [79,80], one study each was from Belgium [35], Denmark [59], Hong Kong [63], Kuwait [73], Singapore [74], Turkey [81], and the United Kingdom [82]; and one study included data from 38 countries [93]. There were 24 studies that included hypertensive patients exclusively (100%) [36, 38, 39, 43-45, 47, 48, 50-52, 54, 56, 58, 66, 71, 72, 75, 78, 81, 87-89, 91].…”