Final results of BIRCOV trial (ARB, ACEI, DRi in COVID-19)
Authors: Ivanov D.D. , Ivanova M.D. , Crestanello T. 
Published: September 2021

Background. The question of the possible effect of the inhibitors of the renin-angiotensin system (iRAS) on hypertensive subjects who fell ill with COVID-19 has been discussed in the literature. SARS-CoV-2 is well-known to use an angiotensin-converting enzyme 2 receptors facilitating virus entry into host cells. There are three possible mechanisms of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) effect in COVID-19 in clinical practice: with worsening, neutral, or helpful function. Considering the different mechanisms of blood pressure reduction by iRAS, one can expect differences in people with COVID-19 receiving these drugs. The purpose of the BIRCOV study is to pinpoint possible clinical and laboratory differences in hypertensive people who received iRAS and suffered from coronavirus infection. Materials and methods. Patient-Oriented Evidence that Matters (POEM) intervention was designed as an open prospective randomized two medical centers trial in subjects suffering from COVID-19 who have been receiving iRAS, either ACEi, ARB, or direct renin inhibitor (DRi) as basic antihypertensive therapy. One hundred and twenty people with stage 1–2 hypertension have been screened, 108 subjects were enrolled in the BIRCOV study. COVID-19 was confirmed by a PCR test; the disease follow-up was divided into 2 periods: up to 12 weeks and up to 24 weeks. The primary outcome measure was as follows: blood pressure (BP) was known one week before COVID-19 onset and was measured during the disease on weeks 2, 4, 12, 24. The secondary outcome measures were clinical features. Subanalysis in patients with chronic kidney disease (CKD) was performed. Results. All patients were randomized into 3 groups who received: ACEi — 42 (39%), ARB — 35 (32%), or DRi — 31 (29%). The BIRCOV trial documented the trend of BP lowering in the first two weeks of the COVID-19 disease with its gradual return to baseline values up to the 12th week. Twenty-three (21%) patients have withdrawn medicine for up to 2 weeks due to severe hypotension. However, the BP values after COVID-19 in most subjects remained lower than the baseline ones for 4 weeks. The use of ACE inhibitors significantly increased the risk of withdrawal compared to DRi (RR 1.648; 95% CI 0.772–3.519; NNT 7.0) and ARB (RR 13.023; 95% CI 1.815–93.426; NNT 2.9) due to COVID-19. The synchronous decline of estimated glomerular filtration rate (eGFR) and systolic BP was more pronounced in CKD patients. The greatest decrease in eGFR was noted in people who have been taking ACEi. The drop in eGFR ranged from 23% in CKD stage 1 to 45% in CKD stage 4. Two people required short-term dialysis. The analysis of secondary outcome points demonstrated that in 23% of people without preceding albuminuria it developed in the A2 range. During 12 weeks of observation, 81% of patients had spontaneous albuminuria reduction. Post-COVID-19 (above 12 weeks) albuminuria remained in 19% of patients, 90% of them had a history of CKD. Patients with preceding CKD had an increase in albuminuria in 78% of cases, and its return to the baseline was observed only in 24% of patients by the 12th week and in 49% of individuals in 24 weeks. Conclusions. People with stage 1–2 hypertension who are receiving chronic iRAS and suffer from COVID-19 may develop hypotension with ACE inhibitors. COVID-19 leads to transient albuminuria and decreased glomerular filtration rate, which is especially dangerous for people with CKD.