Does Stopping RAS Inhibition Affect COVID-19 Course, Recovery?

Older patients with symptomatic SARS-CoV-2 infection and comorbidities who are chronically treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) may experience a faster and better recovery from COVID-19 by discontinuing use of renin–angiotensin system (RAS) inhibitors; however, stopping these therapies does not seem to affect the maximum severity of COVID-19-related illness, according to research findings published in Lancet Respiratory Medicine.

The novel coronavirus responsible for COVID-19 enters human cells by way of the angiotensin-converting enzyme 2 (ACE2), a key regulatory component of the RAS. Previous experimental results suggest inhibition of RAS via pharmacologic means can upregulate expression of ACE2 in various organs, theoretically leading to an adverse effect on the progression of COVID-19. Therefore, concerns have been raised during the pandemic regarding the susceptibility of patients with comorbidities who are treated with ACE inhibitors and ARBs.

Researchers from the ACEI-COVID study, conducted at 25 centers in Austria and Germany, tested whether the discontinuation of chronic ACE inhibitors or ARB treatment could impact the course of established COVID-19. The open-label trial included 204 patients with a recent symptomatic SARS-CoV-2 infection (median age, 75 years) who were treated with ACEIs (56%) or ARBs (44%). Indications for ACEIs and ARBs included diabetes (33%), coronary artery disease (22%), heart failure (9%), and arterial hypertension (98%).

Patients were randomly assigned to either discontinue RAS inhibition (n=104) or continue RAS inhibition (n=100). Approximately 8% (n=8) of patients who discontinued and 12% (n=12) of patients who continued RAS inhibition died within 30 days (P =.42). No difference was observed between the discontinuation and continuation groups in terms of the primary endpoint, which was a composite of the maximum sequential organ failure assessment (SOFA) score and death within 30 days (median [interquartile range] maximum SOFA score, 0.00 vs 1.00, respectively; P =.12).

Discontinuation of RAS inhibition was associated with a significantly lower area under the death-adjusted SOFA score (0.00 vs 3.50; P =.040), mean SOFA score (0.00 vs 0.12; P =.040), and 30-day SOFA score (0.00 vs 0.00; P =.023). By 30 days, a significantly greater proportion of patients who continued RAS inhibition demonstrated signs of organ dysfunction (SOFA score ≥1) or had died (23% in continuation group vs 11% in discontinuation group; P =.017). No significant differences were observed between the 2 continuation and discontinuation groups in terms of rates for mechanical ventilation (10% vs 8%, respectively; P =.87) and intensive care unit admission (19% vs 18%, respectively; P =.96).

The researchers concluded that the decision to discontinue RAS inhibitors “should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options.” Further long-term analysis is needed “to evaluate whether RAS modification during the acute phase might have an effect on the long-term sequelae of SARS-CoV-2,” they added.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Bauer A, Schreinlechner M, Sappler N, et al. Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial. Lancet Respir Med. doi:10.1016/S2213-2600(21)00214-9