Discontinuing vs. Continuing ACEIs, ARBs in Patients Admitted With COVID-19

Quick Takes

  • Discontinuing ACEI or ARB therapy for 30 days did not affect the number of days alive and out of the hospital in patients hospitalized with mild to moderate COVID-19.
  • There were no significant between-group differences in death, cardiovascular outcomes, or COVID-19 progression.
  • Overall, this and other available data do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for their use.

Study Questions:

What is the effect of discontinuation compared with continuation of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on the number of days alive and out of the hospital through 30 days in patients with coronavirus disease 2019 (COVID-19)?

Methods:

The investigators conducted a randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Eligible patients were randomized using a 1:1 allocation ratio to either discontinue or continue ACEI or ARB therapy for 30 days. The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. The comparison between groups was made using generalized additive models for location, scale, and shape with zero-inflated β binomial distribution.

Results:

Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged ≥70 years, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of <94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [standard deviation, 8 days]) versus patients in the continuation group (mean, 22.9 days [standard deviation, 7.1 days]) and the mean ratio was 0.95 (95% confidence interval [CI], 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs. 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs. 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs. 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs. 7.7% in the continuation group), shock requiring vasopressors (8.4% vs. 7.1%, respectively), acute myocardial infarction (7.5% vs. 4.6%), new or worsening heart failure (4.2% vs. 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs. 2.8%).

Conclusions:

The authors concluded that among patients with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue versus continue these medications.

Perspective:

This registry-based randomized clinical trial reports that discontinuing ACEI or ARB therapy for 30 days did not affect the number of days alive and out of the hospital in patients hospitalized with mild to moderate COVID-19. Furthermore, these results were generally consistent across major subgroups. There were no significant between-group differences in death, cardiovascular outcomes, or COVID-19 progression. Overall, this and other available data do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is otherwise an indication for their use.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Acute Kidney Injury, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Coronavirus, COVID-19, Heart Failure, Myocardial Infarction, Primary Prevention, Renal Dialysis, Respiration, Artificial, Respiratory Insufficiency, Shock


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