1. There is no association between ACE inhibitor or ARB use compared with other antihypertensives for risk of COVID-19 hospitalization for outpatients.
2. There is no association between ACE inhibitor or ARB use compared with other antihypertensives for increased mortality risk in patients hospitalized with diagnosis of COVID-19.
Evidence Rating Level: 2 (Good)
Ever since the role of the ACE2 receptor was implicated with the role of viral infection at the beginning of the pandemic, the relationship between angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) with the rate and severity of coronavirus disease-19 (COVID-19) infection has been under study. While most studies show that ACE inhibitor and ARB use do not have an effect on COVID-19 hospitalization, many of these have poor or inappropriate study design, including showing results without adjusting for confounding variables, lacking a comparator, and a lack of long-term follow-up. In this retrospective cohort study, there were two separate sub-studies looking at either outpatients or inpatients using information from public insurance (Medicare Advantage) and private insurance databases. Both models used extensive propensity score matching to adjust for confounders. In the outpatient study, 2263 individuals who had a diagnosis of hypertension and used hypertensive medications (as defined as first- or second-line agents by the American Heart Association guidelines) in the year 2019 and had a positive COVID-19 test as an outpatient between March 6, 2020 to May 3, 2020 were included. For the outpatient study, there was no association of ACE inhibitors (HR 0.77, CI 0.52-1.13, p=0.18) or ARBs (HR 0.88, CI 0.61-1.26, p=0.48) with hospitalization compared to other antihypertensive medications. When comparing providers, ACE inhibitors were associated with a lower hospitalization risk in older public insurance compared to the younger private insurance group (HR 0.61, CI 0.41-0.93, p=0.02 vs. HR 2.14, CI 0.85-5.60, p=0.12). In the inpatient study, there was also no association of ACE inhibitor or ARB use for in-hospital mortality (HR 0.97, CI 0.81-1.16, p=0.74 and HR 1.15, CI 0.95-1.38, p=0.15) compared to other antihypertensive medications. Strengths of this study include extensive analysis for confounding, a large sample size, and longer follow-up. Limitations include that the proportion of patients with sufficient data to be included in the propensity matched groups was smaller than the original population. There was also some uncertainty in whether medication was continued or discontinued during acute illness and whether that impacted patient outcomes; neither will all individuals necessarily seek care despite having symptoms. These results further enforce that there is no association of the use of these antihypertensive medications to increased risk of contracting COVID-19 or having higher mortality. These results also discourage ACE inhibitor or ARB use as prophylaxis against severe disease.
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