By Sally Robertson, B.Sc

Researchers in India have conducted a meta-analysis investigating the effects of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes among patients with COVID-19.

They say their data suggest that continuing these treatments among this patient group is not only safe but significantly reduces the risk of severe disease and death.

Furthermore, “the findings of this meta-analysis reinforce the recommendations issued by the various agencies to continue ACEi/ARB in patients with comorbidities who contract COVID-19,” they write.

Urgent need for a clinical trial
The team of consultant endocrinologists says the findings highlight the urgent need for a randomized controlled trial to confirm the potential beneficial effects of using ACEi/ARB, but that in the meantime their meta-analysis could help to reassure clinicians until further information becomes available.

A pre-print version of the paper can be accessed in the medRxiv server, while the article undergoes peer review.

The concerns that have arisen
As coronavirus disease 2019 (COVID-19) continues to sweep the globe, it has become clear that patients with pulmonary disease, cardiac conditions, renal disease, hypertension or diabetes are not only at an increased risk of contracting the causative agent (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) but are also at a greater risk of severe disease and death.

The ACEi/ARB regimen is commonly used to treat such patients, but since the virus uses the angiotensin-converting enzyme 2 (ACE2) to enter cells, concerns have arisen regarding the potential health outcomes among patients with COVID-19.

ACE2 is found on the surface of cells in the heart, kidney, stomach, intestine, and lungs. Some preclinical studies have shown that the use of ACEi/ARBs upregulates the expression of ACE2, leading researchers and physicians to question whether these medications might increase the risk of SARS-CoV-2 infection and the severity of the disease.

Kalyan Kumar Gangopadhyay (Fortis & Peerless Hospital, Kolkata) and colleagues say some studies have also failed to establish the effects that these medications have on alveoli in the lungs and that more evidence is urgently needed to guide physicians’ decisions as the rapidly progressing COVID-19 pandemic continues to spread.

The team’s meta-analysis
Now, Gangopadhyay and colleagues have pooled data available from five studies of patients infected with SARS-CoV-2 and compared outcomes among 308 who were taking ACEi/ARB and 1,172 who were not.

“To our knowledge, this is the first meta-analysis on the effect of ACEi/ARB in patients with COVID-19 on clinically relevant end-points,” says the team.

They searched the Cochrane Library, PubMed, Embase, ClinicalTrial.gov, and medRxivarchives for articles published up until April 21st. They analyzed the effects of ACEi/ARB use on severity of disease, risk for hospitalization and death, compared with non-use.

The researchers add that “depending on the degree of heterogeneity, fixed or random effect model was selected to calculate effect size (odds ratio).”

The researchers report that patients with COVID-19 who were taking ACEi/ARB were at a 44% lower risk of developing severe disease and a 62% lower risk of death compared with those not taking the medications.

The likelihood of hospitalization was also reduced by 19% among those who did take them, although this risk reduction did not reach statistical significance.

The reported benefits support recommendations made by various agencies
The team says the statistically significant benefits identified in the analysis support recommendations made by the European Societies of Cardiology, the American Heart Association, the Heart Failure Society of America, the American College of Cardiology and International Society of Hypertension that ACEi/ARB treatment should be continued among patients with COVID-19.

“The reduction in the odds of death and odds of risk of developing severe disease is not only reassuring concerning the safety of ACEi/ARB in patients with COVID-19 but also point towards the urgent need for an adequately powered RCT to confirm these benefits,” writes the team.

The researchers say that, in the meantime, their analysis adds to current evidence supporting the safety of treating COVID-19 patients with ACEi/ARB and the potential reduction in risk for severe disease and death.

“This meta-analysis, highlighting the safety and possibly beneficial effects of ACEi/ARB, shall help physicians use ACEi/ARB in patients with COVID-19 until further information becomes available,” they conclude.