Effects of renin‐angiotensin‐aldosterone system inhibitors on disease severity and mortality in patients with COVID‐19: A meta‐analysis

Abstract

To investigate the effects of renin‐angiotensin‐aldosterone system (RAAS) inhibitors on the prognosis in patients with coronavirus disease 2019 (COVID‐19). A meta‐analysis was performed. We systematically searched PubMed, the Cochrane Library, the Web of Science, EMBASE, medRxiv, and bioRxiv database through October 30, 2020. The primary and secondary outcomes were mortality and severe COVID‐19, respectively. We included 25 studies with 22,734 COVID‐19 patients, and we compared the outcomes between patients who did and did not receive angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs). The use of ACEIs/ARBs was not associated with higher risks of severe disease (odds ratio [OR] = 0.89; 95% confidence interval [CI]: 0.63, 1.15; I 2 = 38.55%), mechanical ventilation (OR = 0.89; 95% CI: 0.61, 1.16; I 2 = 3.19%), dialysis (OR = 1.24; 95% CI: 0.09, 2.39; I 2 = 0.00%), or the length of hospital stay (SMD = 0.05; 95% CI: −0.16, 0.26; I 2 = 84.43%) in COVID‐19 patients. The effect estimates showed an overall protective effect of ACEIs/ARBs against mortality (OR = 0.65; 95% CI: 0.46, 0.85; I 2 = 73.37%), severity/mortality (OR = 0.69; 95% CI: 0.43, 0.95; I 2 = 22.90%), transfer to the intensive care unit among COVID‐19 patients with hypertension (OR = 0.36, 95% CI: 0.19, 0.53, I 2 = 0.00%), hospitalization (OR = 0.79; 95% CI: 0.60, 0.98; I 2 = 0.00%), and acute respiratory distress syndrome (OR = 0.71; 95% CI: 0.46, 0.95; I 2 = 0.00%). The use of RAAS inhibitor was not associated with increased mortality or disease severity in COVID‐19 patients. This study supports the current guidelines that discourage the discontinuation of RAAS inhibitors in COVID‐19 patients.

Hypertension and COVID-19: Ongoing Controversies

“…This hypothesis was supported by initial findings that these medications were more frequently used in COVID-19 patients with cardiac injury or in those with severe form of disease ( 8 , 9 ). Nevertheless, later reports failed to show any negative relationship between adverse outcome and use of ACEI and ARB in COVID-19 patients ( 10 – 13 ).…”

“…There was a long discussion regarding the impact of antihypertensive therapy in COVID-19 patients and particularly of angiotensin-converting enzyme inhibitors (ACEI) and blockers of angiotensin I receptors (ARB). After initial reports that showed higher prevalence of use of these medications in COVID-19 patients with cardiac injury and more severe course of disease ( 8 , 9 ), numerous original studies and meta-analysis reported no relationship with severity or mortality in COVID-19 patients ( 10 , 11 ) or even benefit of taking renin-angiotensin-aldosterone inhibitors in COVID-19 patients ( 12 , 13 ).…”

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review

“…Numerous studies suggest that ACEi/ARB therapy does not influence negatively mortality or susceptibility to virus infection [ 73 , 74 , 75 , 76 , 77 ]. Furthermore, evidence of ACEi/ARB effectiveness is reported in publications based on meta-analysis as well [ 78 , 79 ]. The recent BRACE-CORONA trial suggests that treatment interruption does not positively affect the survival of COVID-19 patients, thus ACEi/ARB therapy should be continued [ 80 ].…”

Targeting the coronavirus SARS-CoV-2: computational insights into the mechanism of action of the protease inhibitors lopinavir, ritonavir and nelfinavir

“…The first outbreak of this new disease originally took place in the city of Wuhan (China), rapidly spreading in the southeast of Asia and, recently, in other continents like Europe, North America and Africa 1 . The astonishing rate at which COVID is expanding compared to previous coronavirus related diseases (SARS-CoV and MERS-CoV), in conjunction with the absence of approved drugs or effective therapeutic approaches for its treatment, has gathered the attention of the international community, which is promoting a cooperative effort to face this emergency 3 , 4 . On January 2020 indeed, the International Health Regulations Emergency Committee of the World Health Organization declared the outbreak a “public health emergency of international concern” in responding to SARS-CoV-2.…”

“…In the meantime, however, a great effort involves the targeting of non-structural viral proteins which are instead essential for the viral replication and the maturation processes, thus representing a crucial and specific target for anti-COVID drug development 3 , 10 . In this regard, the crystallographic structure of the SARS-CoV-2 main protease (M pro ), also known as C30 Endopeptidase, was elucidated and made available to the scientific community with impressive timing, just a few weeks after the first COVID-19 outbreak (PDB ID: 6LU7).…”