Do ACE Inhibitors Have a Protective Effect in People with COVID-19?

ACE Inhibitors and COVID-19

ACE inhibitors (e.g., perindopril) are among the first-choice drugs in the treatment of arterial hypertension. Angiotensin-converting enzyme 2 (ACE2) likely serves as a receptor for the SARS-CoV-2 coronavirus, hence arterial hypertension is considered one of the main risk factors for the severe course of COVID-19. ACE inhibitors could potentially influence the course and prognosis of the disease.

Meta-Analysis

The authors examined observational studies of patients hospitalized for COVID-19 published by May 9, 2020, which analyzed data from patients with arterial hypertension as a comorbidity for which they were treated with ACE inhibitors and/or sartans. They included only studies that reported clinical outcomes of hospitalized patients (severe/fatal course of the disease vs. no severe course) in the meta-analysis.

Ultimately, they selected 16 studies involving a total of 24,676 individuals with COVID-19 infection. All cases were adults, both genders were represented, and the average age of subjects in each study ranged from 50 to > 70 years. Data from 8 studies came from patients in China, 4 studies included patients from North America, 3 studies involved patients from Europe, and one worked with data from an international registry.

Results

The results of the studied research demonstrated a protective effect of renin-angiotensin-aldosterone system (RAAS) inhibitors, i.e., ACE inhibitors and sartans, in patients with COVID-19. The risk of death or severe course decreased by approximately 23% (odds ratio [OR] 0.768; 95% confidence interval [CI] 0.651−0.907; p = 0.0018). In patients treated with ACE inhibitors, the risk reduction was greater (OR 0.652; 95% CI 0.478−0.891; p = 0.0072) than in patients using sartans (OR 0.810; 95% CI 0.629−1.044; p = NS). Studies involving patients from Europe and North America showed higher heterogeneity of results compared to studies involving patients from China.

Discussion

The analysis of the studies did not show any increased risk of severe course of COVID-19 in patients with arterial hypertension using ACE inhibitors, on the contrary, a mild protective effect of these drugs was noted. It positively influenced both the severity of the course and the prognosis of the disease. A possible limitation of the analysis may be the fact that none of the studies were randomized. The presence of other comorbidities, such as type 2 diabetes mellitus and obesity, could have also been significant in terms of study outcomes. The exact protective mechanism of ACE inhibitors remains speculative as the pathophysiology of the severe course of COVID-19 is not yet fully understood.

Conclusion

The study results suggest that therapy with ACE inhibitors in patients with arterial hypertension who contracted COVID-19 should not be discontinued. Moreover, uncontrolled hypertension worsens the prognosis of the disease and increases the risk of severe COVID-19 course. Further studies and analyses are needed to refine and potentially generalize the results for the general population or to stratify by gender.

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Source: Pirola C. J., Sookoian S. Estimation of renin-angiotensin-aldosterone-system (RAAS)-inhibitor effect on COVID-19 outcome: a meta-analysis. J Infect 2020; 81 (2): 276−281, doi: 10.1016/j.jinf.2020.05.052.