Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

“…However, several associations have recommended not to suspend these therapies [61,[111][112][113][114], and these recommendations have been confirmed by three recent studies: the first one performed on 362 hypertensive patients showed that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 [91]; the second one verified the effects of ACEI/ARB on 1128 hypertensive COVID-19 patients, showing that the use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users [115]; the third one demonstrated that without increasing the risk for SARS-CoV-2 infection, ACEI/ARB outcompeted other antihypertensive drugs in reducing inflammatory markers like C-reactive protein and procalcitonin levels in COVID-19 patients with preexisting hypertension [116]. Consistent with these findings, three observational studies performed in different populations and with different designs [117][118][119] (published in the same issue of the New England Journal of Medicine), arrived at the consistent message that the continued use of ACEI/ARB is unlikely to be harmful in COVID-19 patients. Notably, in one of these studies [117], the use of either ACEI or statins-two classes of drugs that are known to ameliorate endothelial function [120][121][122][123]-was found to be associated with a lower risk of in-hospital death than non-use.…”

“…Consistent with these findings, three observational studies performed in different populations and with different designs [117][118][119] (published in the same issue of the New England Journal of Medicine), arrived at the consistent message that the continued use of ACEI/ARB is unlikely to be harmful in COVID-19 patients. Notably, in one of these studies [117], the use of either ACEI or statins-two classes of drugs that are known to ameliorate endothelial function [120][121][122][123]-was found to be associated with a lower risk of in-hospital death than non-use.…”

Renin-angiotensin system inhibitors in COVID-19

“…Mehra et al report data from 8,910 patients in 11 countries, and neither ACE inhibitors nor ARBs were associated with increased mortality; a secondary analysis restricted to patients with a history of hypertension also did not show any harm with these medications. 9 Mancia et al report data from 6,272 patients in Italy, compared to 30,759 matched controls, and neither ACE inhibitors nor ARBs were associated with the likelihood of SARS-CoV-2 infection; an additional analysis of severe infections also did not fi nd any association with these medications. 10 Reynolds et al report data from 5,894 patients in New York with propensity score matching analysis among all patients and in those with hypertension, examining 5 different antihypertensive medication classes (ACE inhibitors, ARBs, beta blockers, calcium channel blockers, and thiazide diuretics)-no association was found for any these medication classes with likelihood of infection or risk of severe infection.…”

“…The counter-regulatory pathway involves angiotensin-converting enzyme 2 (ACE2), which cleaves angiotensin I to form angiotensin (1)(2)(3)(4)(5)(6)(7)(8)(9) and also cleaves angiotensin II to form angiotensin (1)(2)(3)(4)(5)(6)(7). This serves to decrease angiotensin II, and angiotensin (1-7) further affects vasodilation by binding to the Mas receptor.…”

COVID-19 — Toward a comprehensive understanding of the disease

“…Thus, it is almost certain that acute cardiovascular complications are not secondary to lung disease. Although it was hypothesized that the treatment strategy based on the usage of the renin-angiotensin-system inhibitors, i.e., ACE inhibitors or angiotensin receptor blockers (ARBs) may promote SARS-CoV-2 binding to ACE2, large body of evidence does not confirm these concerns [104][105][106][107]. Notably, in preclinical studies, ARBs appeared to have a potentially protective effect [108].…”