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ACE or ARB Drugs Do Not Boost Risk of COVID-19 or Flu
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Mark Mascolini
Large studies in the United States, Italy, and the United Kingdom (UK) should ease fears that taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) raise the risk of COVID-19 or influenza [1-3]. In fact the UK study found that these popular antihypertensives lower flu risk.
Because SARS-CoV-2, the COVID-19 virus, uses angiotensin-converting enzyme 2 (ACE-2) to enter target cells, some feared that drugs interfering with the renin-angiotensin-aldosterone system—like ACE inhibitors and ARBs—may make COVID-19 more likely [1,2]. Influenza A (including subtypes H7N9, H1N1, and H5N1) uses the ACE-2 receptor to mediate lung damage [3].
Researchers at New York University (NYU) in New York City analyzed medical records of everyone tested for COVID-19 between March 1 and April 15, 2020 [1]. Among 12,594 people tested, 5894 (46.8%) had COVID-19 and 1002 (17% of 5894) had severe illness (intensive care, mechanical ventilation, or death). More than one third of patients (4357, 34.6% of 12,594) had a history of hypertension, of whom 2573 (59.1%) had COVID-19 and 634 (24.6% of 2573) had severe COVID-19.
The NYU team assessed relations between previous treatment with ACE inhibitors, ARBs, beta-blockers, calcium-channel blockers, or thiazide diuretics and a positive or negative COVID-19 test plus the likelihood of severe illness among those with COVID-19. Bayesian methods showed no association between any medication class and greater chance of a positive COVID-19 test or a substantially increased risk of severe COVID-19.
In Italy’s Lombardy region, researchers matched 6272 people with SARS-CoV-2 infection to 30,759 people without the virus by age, sex, and municipality [2]. Both groups averaged 68 years in age and 37% were women. People with COVID-19 took ACE inhibitors and ARBs more often than the control group because they had a higher prevalence of cardiovascular disease. But statistical analysis detected no association between ARBs or ACE inhibitors and COVID-19 risk overall or COVID-19 risk in people with a severe or fatal disease course.
UK researchers used electronic health records to determine flu incidence in adults who got an ACE inhibitor, an ARB, or neither from 1998 through 2016 [3]. While 700,994 people got an ACE inhibitor prescription, 230,028 were prescribed an ARB and 4,742,017 got neither drug or the direct renin inhibitor aliskiren. After a median 8.7 years of follow-up, an analysis adjusted for age, sex, smoking history, influenza vaccination, obesity, and 12 comorbidities determined that people taking an ACE inhibitor had a one third lower risk of flu than those who did not (adjusted hazard ratio [aHR] 0.66, 95% confidence interval [CI] 0.62 to 0.70). Taking an ARB halved the flu risk (aHR 0.52, 95% CI 0.47 to 0.57). Further analysis showed that the longer people took ACE or ARB agents, the lower their flu risk.
Professional societies and expert panels recommend not stopping ACE inhibitors or ARBs for fear that they may raise the risk of COVID-19 infection, severity, or death [4-6].
References
1. Reynolds HR, Adhikari S, Pulgarin C, et al. Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2008975. https://www.nejm.org/doi/full/10.1056/NEJMoa2008975
2. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2006923. https://www.nejm.org/doi/full/10.1056/NEJMoa2006923
3. Chung SC, Providencia R, Sofat R. Association between angiotensin blockade and incidence of influenza in the United Kingdom. N Engl J Med. May 8, 2020. DOI: 10.1056/NEJMc2005396. https://www.nejm.org/doi/full/10.1056/NEJMc2005396
4. American College of Cardiology. HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. March 17, 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19
5. European Society of Cardiology. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. March 13, 2020.
6. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med 2020;382:1653-1659.
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