Candesartan may help fight COVID-19

Use of the angiotensin receptor blocker (ARB) candesartan in the treatment of COVID-19 appears to shorten hospital stay overall, as well as speed up lung injury resolution and viral clearance for patients without obesity, according to the results of a study from Indonesia.

“The present study supports the use of ARBs in patients without comorbidities such as hypertension or diabetes, in view of the fact that [such drugs] provide protection against lung injury or cardiovascular complications,” the investigators said.

ARBs, along with ACE inhibitors, have been shown to increase the number of CD3 and CD8 T cells, with a decreased peak viral load, compared with other blood pressure (BP)-lowering drugs. Furthermore, these drugs may mitigate the cardiovascular injuries, pre-existing or new, commonly encountered in patients with COVID-19, as the investigators pointed out. [Emerg Microbes Infect 2020;9:757-760; J Stroke Cerebrovasc Dis 2020;29:104949; Int J Infect Dis 2021;105:351-356; Int J Infect Dis 2021;105:312-318]

In the present study, a total of 75 COVID-19 patients (mean age 41 years, 70.67 percent male, mean body mass index 23.35 kg/m²) in Siloam Kelapa Dua Hospital in Banten, Indonesia, participated. Of these, 40 received standard care alone (control) and 35 agreed to receive additional candesartan. The ARB was given at 4–32 mg once daily, titrated according to BP tolerance. The standard care regimen consisted of azithromycin 500 mg once daily or levofloxacin 750 mg once daily, hydroxychloroquine 400 mg once daily, and vitamin C 1,000 mg.

Some of the patients had hypertension (9.3 percent) and diabetes (5.3 percent), and 12 percent were current smokers. COVID-19 was mild-to-moderate in 89.33 percent of the population and severe in 10.67 percent. All patients were ARB-naïve, except for one in the control group who had a history of candesartan use but had not been actively taking the drug for months. None of the patients required intensive care.

During the 14-day follow-up, patients in the candesartan group had a significantly shorter hospital stay compared with those in the control group. Multivariate Cox regression analysis confirmed that the use of the ARB increased the probability of being discharged sooner by more than twofold (adjusted hazard ratio [HR], 2.47, 95 percent confidence interval [CI], 1.16–5.29), with no increased risk of intensive care. [Int J Infect Dis 2021;doi:10.1016/j.ijid.2021.05.019]

In the subgroup of patients with normal weight, those who received candesartan vs the standard regimen alone had a shorter time to negative swab (adjusted HR, 2.40, 95 percent CI, 1.08–5.09) and shorter time to improvement in chest X-ray (adjusted HR, 2.82, 95 percent CI, 1.13–7.03).

According to the investigators, the additional benefit observed among patients with normal weight may be explained by the proinflammatory state in people with obesity, which can weaken the effect of candesartan. “Additionally, obese patients express more ACE2 receptors … [and] a higher number of ACE2 receptors may translate to an increased candesartan dose requirement.”

The study was limited by its open-label design, the small sample size, and the potential self-selection bias, although the investigators pointed out that there was no significant difference in the baseline characteristics of the two groups.

“Randomized controlled trials should be conducted in patients with severe COVID-19 to evaluate the benefit of candesartan in terms of mortality and ICU admission,” as well as to establish whether it is more effective in patients without obesity, the investigators said.