Renin-angiotensin-aldosterone system inhibitors do not affect COVID-19 risk

1. Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) were not shown to affect the risk of COVID-19.

2. ACE inhibitors and ARBs were shown to be more frequently used among coronavirus disease 2019 (COVID-19) patients.

Evidence Rating Level: 3 (Average)

Study Rundown: Angiotensin-converting enzyme 2 (ACE2), a membrane bound aminopeptidase abundantly expressed in the lungs and heart, is used by coronaviruses for entrance into the cell. ACE inhibitors and ARBs increase ACE2 expression and block the renin-angiotensin-aldosterone system (RAAS). Therefore, there has been concern that using these drug therapies can alter infection susceptibility. As such, the study evaluated the association between RAAS blockers and the risk of COVID-19. The study collected patient data from resident in Lombardy, Italy capturing COVID-19 infection status, underlying cardiovascular disease, and cardiovascular medication use. No evidence was found to support the use of ACE inhibitors or ARBs to be independently associated with the risk of COVID-19. This retrospective study was limited by drug use data was assessed through prescriptions. As such, actual drug consumption could not be assessed. Another limitation was the doses studied were those available in Italy, which may not reflect the doses present in other countries. Nonetheless, this study was strengthened by conducting a case-control trial to understand the relationship between underlying RAAS blocker drug use and COVID-19 risk. For physicians, these findings highlight the importance of continuing patients on their RAAS blockers to maintain cardiovascular health as these medications likely do not alter COVID-19 risk.

Click to read the study in NEJM

Relevant Reading: Renin–Angiotensin–Aldosterone System Inhibitors in Patients with COVID-19

In-Depth [case-control study]: This case-control study retrospectively collected data from 37,031 patients from Lombardy, Italy. Data for diagnoses and services were collected from the National Health Service database inpatient and outpatient electronic health records and point-of-care data entry for procedures. Data for medications were collected from the Anatomical Therapeutic Chemical codes. Cardiovascular conditions were collected based on codes from the International Classification of Diseases, 9th Revision, Clinical Modification, and COVID-19 positivity was defined as at least two positive nasopharyngeal swabs confirmed through real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR). Inclusion criteria included: patients 40 years of age or older and COVID-19 diagnosis between February 21, 2020, to March 11, 2020. Exclusion criteria included: patients who were not beneficiaries of the Regional Health Service and younger than the age of 40. The primary outcome was the evaluation between the relationship of RAAS blocker drug therapy with the risk of COVID-19. Overall, the patients were older and more likely to be male. RAAS blockers were prescribed more frequently to the case patients compared to the control patients. Specifically, ACE inhibitors 23.9% of case patients were prescribed the medication compared to 21.4% of control patients. ARBs prescriptions in the case patients was 22.2% compared to 19.2% in the control group. In regard to RAAS blockers, ACE inhibitors (0.96, 95% confidence interval [CI], 0.87 to 1.07) and ARBs (0.95, 95% CI, 0.86 to 1.05) did not have a significant association with COVID-19 risk. Furthermore, other antihypertensive medications such as beta blockers (0.99, 95% CI, 0.91 to 1.08) and thiazides (1.03, 95% CI, 0.86 to 1.23), also, did not have a significant association with COVID-19 risk. Additionally, neither monotherapy (1.03, 95% CI, 0.90 to 1.18) nor combination therapy (0.99, 95% CI, 0.90 to 1.09) use of the antihypertensive medications showed significant association with COVID-19 risk. Taken together, the study concluded the use of RAAS blocker and other antihypertensive medications did not change the risk of COVID-19 infections.

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