Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial
RCT (n=204) found no significant difference between discontinuation and continuation of RAS inhibiton for maximum sequential organ failure assessment (SOFA) score at 30 days, though more who continued had signs of organ dysfunction or were dead (11% vs 23%, p=0·017).
Source:
The Lancet Respiratory Medicine
SPS commentary:
A related commentary notes that this trial is specific in its inclusion of an older population who have comorbidities such as overweight, chronic obstructive pulmonary disease, hypertension, and heart failure. This was not intended by the design, but it rather reflects the characteristics of the patients admitted to hospital during the first waves of the disease in Europe.
Although the findings of this study confirm the results of the BRACE CORONA and the REPLACE COVID trials, i.e. there is no effect of RAS blockers on the severity and evolution of the disease up to 30 days, after its peak, the mean sequential organ failure assessment scores in the discontinuation group decreased more rapidly and reached lower values than in the continuation group. Therefore discontinuation might lead to a faster and better recovery among these older, high-risk patients with COVID-19.
The commentary notes however, that this conclusion should be interpreted with great caution, considering that it derives from secondary analyses in a study that did not meet its primary endpoint. Practitioners should also note that, although there is no safety signal in the discontinuation group, the risk of RAS blockers discontinuation is well known and the follow-up was probably too short to detect any difference in the adverse events rate between the two groups.
The commentary concludes that although the study adds more data to the existing evidence showing that RAS blockers should not be systematically discontinued in patients with COVID-19, it unfortunately leaves more questions than answers.
Overall, the study authors note the decision to continue or discontinue should be made on an individual basis, taking the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options into account.