Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in patients with COVID-19: a systematic review and meta-analysis

Abstract

Background: The use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in patients with coronavirus disease 2019 (COVID-19) given their interaction with the angiotensin-converting enzyme-2 (ACE-2) receptor remains controversial.. Objective: To investigate the impact of ACEI/ARB on COVID-19 disease severity and mortality through a systematic review and meta-analysis. Methods: We searched PubMed and CINAHL databases as well as pre-print servers for studies investigating usage of ACEIs/ARBs in patients with COVID-19 compared to a control group of COVID-19 patients without ACEI/ARB use. COVID-19 related severity of disease, and death were identified as end points. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated using random-effects model. Results: 21 studies were included in the meta-analysis. For mortality with ACEI/ARB use, the pooled odds ratio was 1.29 [0.89-1.87] p = 0.18 with heterogeneity of 91%, while the pooled OR for COVID-19 severity was 0.94 [0.59-1.50] p = 0.81 with heterogeneity of 89% (Figure 2). In combining both mortality and severe disease outcomes, the pooled odds ratio was 1.09 [0.80-1.48] p = 0.58 but with heterogeneity of 92%. Expert Opinion: Even on pooled analysis of both un-adjusted data, adjusted data(studies with matched controls) and taking into account factors such as risk of bias of studies via meta regression and sensitivity analyses, the results hold true that ACEI/ARB use is not associated with COVID-19 disease severity or mortality. To look for any potential beneficial effects, randomized controlled trials are needed. Conclusion: use of ACEI/ARB was not associated with increased mortality or severe COVID-19.

Real‐World Evidence for Assessing Pharmaceutical Treatments in the Context of COVID‐19

“…For example, because of SARS-CoV-2's interactions with angiotensin converting enzyme receptors, there have been a number of studies on how angiotensin converting enzyme inhibitor medications may impact the risk of a mild COVID-19 case progressing to more serious illness among patients who were taking these drugs for their cardiovascular effects when they were diagnosed with COVID-19. [15][16][17] There has also been considerable interest regarding whether hydroxychloroquine or other drugs could be prescribed as early treatment to prevent serious disease among patients testing positive for COVID-19. When assessing study validity of the treatment effectiveness in this context it helps to differentiate between studies of treatments used for conditions other than COVID in patients who then happen to be infected vs. medications that are specifically prescribed after an infection in the hope to alleviate the presentation of COVID.…”

“…Much of the work on outpatient medications used for COVID‐19 has focused on how existing medications may lower disease severity among infected patients. For example, because of SARS‐CoV‐2’s interactions with angiotensin converting enzyme receptors, there have been a number of studies on how angiotensin converting enzyme inhibitor medications may impact the risk of a mild COVID‐19 case progressing to more serious illness among patients who were taking these drugs for their cardiovascular effects when they were diagnosed with COVID‐19 15–17 . There has also been considerable interest regarding whether hydroxychloroquine or other drugs could be prescribed as early treatment to prevent serious disease among patients testing positive for COVID‐19.…”

Inpatient Omission of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With Morbidity and Mortality in Coronavirus Disease 2019

“…Several meta-analyses have concluded that antecedent ACEi/ARB prescription did not predispose to worsened outcomes in COVID-19. [6][7][8] Others concluded that prior ACEi/ARB use reduced the risk of mortality and ICU admission, and decreased length of stay. [9][10][11][12][13][14] There is theoretical basis for both deleterious and protective effects of these agents in SARS-CoV-2 infection.…”

“…Broadly these suggest that antecedent ACEi/ARB therapy is not associated with worsened outcomes in COVID-19, and that their use might confer certain protective benefits. [6][7][8][9][10][11][12][13][14] The impact of ACEi/ARB provision during acute COVID-19 illness has been inadequately examined. To date few studies have attempted to address this question.…”

The Importance of Antihypertensive and Lipid-Lowering Therapy in the Treatment of Patients with a New Coronavirus Infection COVID-19

“…В настоящее время имеются неоспоримые доказательства того, что отказ от планового приема ингибиторов ангиготензин-превращающего фермента (иАПФ) или блокаторов рецепторов к ангиотензину (БРА) существенно увеличивает риск сердечно-сосудистых катастроф у пациентов с новой коронавирусной инфекцией, вызванной вирусом SARS-CoV-2 [8]. Применение этих лекарственных препаратов способствует уменьшению выраженности фиброза миокарда, улучшению функции эндотелия, активации медиаторов окислительного стресса и уменьшению воспаления, что обеспечивает кардиопротективные эффекты при COVID-19.…”