Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19

Abstract Background A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting–enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. Methods We carried out a population-based case–control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. Results Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. Conclusions In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

[1]  Ji-Guang Wang,et al.  Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19 , 2020, Cardiovascular research.

[2]  Marc A Pfeffer,et al.  Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19 , 2020, The New England journal of medicine.

[3]  Tao Guo,et al.  Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19) , 2020, JAMA cardiology.

[4]  W. Gong,et al.  Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. , 2020, JAMA cardiology.

[5]  D. Batlle,et al.  Renin-Angiotensin System Blockers and the COVID-19 Pandemic , 2020, Hypertension.

[6]  A. Verma,et al.  COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? , 2020, JAMA.

[7]  G. Onder,et al.  Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. , 2020, JAMA.

[8]  O. Pfister,et al.  SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19? , 2020, European heart journal.

[9]  Michael Roth,et al.  Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? , 2020, The Lancet Respiratory Medicine.

[10]  M. Esler,et al.  Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? , 2020, Journal of hypertension.

[11]  Xiang Xie,et al.  COVID-19 and the cardiovascular system , 2020, Nature Reviews Cardiology.

[12]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[13]  K. Yuen,et al.  Clinical Characteristics of Coronavirus Disease 2019 in China , 2020, The New England journal of medicine.

[14]  Kai Zhao,et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin , 2020, Nature.

[15]  Ting Yu,et al.  Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study , 2020, The Lancet.

[16]  Victor M Corman,et al.  Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[17]  G. Corrao,et al.  A new population-based risk stratification tool was developed and validated for predicting mortality, hospital admissions and healthcare costs. , 2019, Journal of clinical epidemiology.

[18]  D. Pennell,et al.  Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial , 2019, The Lancet.

[19]  G. Mancia,et al.  Early cardiovascular protection by initial two-drug fixed-dose combination treatment vs. monotherapy in hypertension , 2018, European heart journal.

[20]  Akshay S. Desai,et al.  Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impa , 2018, Circulation. Heart failure.

[21]  M. Woodward,et al.  Risks associated with permanent discontinuation of blood pressure-lowering medications in patients with type 2 diabetes , 2016, Journal of hypertension.

[22]  G. Mancia,et al.  Adherence With Antihypertensive Drug Therapy and the Risk of Heart Failure in Clinical Practice , 2015, Hypertension.

[23]  G. Mancia,et al.  Generating evidence from computerized healthcare utilization databases. , 2015, Hypertension.

[24]  M. Lai,et al.  Angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers and pneumonia risk among stroke patients , 2012, Journal of hypertension.

[25]  D. Batlle,et al.  Pharmacologic modulation of ACE2 expression , 2008, Current hypertension reports.

[26]  Martin Paul,et al.  Physiology of local renin-angiotensin systems. , 2006, Physiological reviews.

[27]  D. Diz,et al.  Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers on Cardiac Angiotensin-Converting Enzyme 2 , 2005, Circulation.

[28]  John L. Sullivan,et al.  Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus , 2003, Nature.