Repurpose Beta-Blocker for Severe COVID?

 Intravenous metoprolol for severely ill COVID-19 patients on intensive mechanical ventilation was associated with less lung inflammation and better oxygenation, a randomized pilot study in Spain found.

Among 20 patients on ventilation for COVID-related acute respiratory distress syndrome (ARDS), those assigned to 3 days of metoprolol saw lower neutrophil counts in bronchoalveolar lavage at day 4 compared with those who did not receive the beta-blocker (median 14 vs 397 neutrophils/μl, respectively; P=0.016), reported Borja Ibanez, MD, PhD, of the National Center of Cardiovascular Research in Madrid, and colleagues.

Compared with baseline, oxygenation (PaO2:FiO2) improved for patients on IV metoprolol (median 130 to 267; P=0.003), while no change was seen without the treatment, the authors wrote in the Journal of the American College of Cardiology.

"Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic," the authors said.

Metoprolol also decreased neutrophil extracellular traps content and other markers of lung inflammation, such as IL-8, versus baseline, and the intervention group spent fewer days on mechanical ventilation, though this did not reach statistical significance (15.5 vs 21.9 days, P=0.17).

"There is a growing body of literature regarding the role of beta-blockers in a wide variety of critically ill patients with sepsis and before major surgery, acute respiratory distress syndrome, and traumatic brain injury," noted Mourad Senussi, MD, MS, of Baylor St. Luke's Medical Center in Houston, in an accompanying editorial.

"Although a small-sized, single-center study amid a multitude of others exploring potential treatment modalities for COVID-19 -- this study uses a readily available, safe, and inexpensive medication; has a simple study design; and, most importantly, shows biological plausibility," Senussi wrote.

He also noted the selection bias in the study, as "only those patients who are hemodynamically stable enough can receive beta-blockers."

Anywhere from 6% to 18% of COVID cases result in ARDS, requiring intensive care unit (ICU) admission and use of intensive mechanical ventilation, Ibanez and colleagues explained. As the virus rapidly replicates, ARDS develops from activated neutrophils that infiltrate the alveolar space of the lungs. Metoprolol can reduce inflammation, thereby lowering the risk of cardiovascular events.

"Administration of IV beta-blockers has largely been proven to be safe except for patients with acute pump failure," they noted.

From October 2020 to January 2021, the MADRID-COVID trial (Intravenous Metoprolol in Respiratory Distress Due to COVID-19) randomized patients with COVID-19-associated ARDS to IV metoprolol (n=12; 15 mg daily for 3 days) or no metoprolol (n=8). One patient in the intervention arm only received 2 days of metoprolol due to bradycardia.

The cohort included adults up to age 80 (median 60) with SARS-CoV-2 infection confirmed by RT-PCR, systolic blood pressure ≥120 mm Hg, and a minimum heart rate of 60 bpm. Patients were required to be on mechanical ventilation for fewer than 3 days.

The study's main outcomes were metoprolol's effect on lung inflammation and respiratory function. Before and after randomization, patients in both groups underwent bronchoalveolar lavage. ICU patients were given anticoagulants, corticosteroids, acetylcysteine, and melatonin.

Baseline patient characteristics did not significantly differ between groups. For comorbidities, hypertension (30%) and dyslipidemia (30%) were most common. One-fourth of patients were previously taking renin-angiotensin system inhibitors.

At baseline, there were no between-group differences in neutrophil count. No side effects were reported from the use of metoprolol. While most were discharged, one patient from each group died.

Other limitations of the study included the open-label treatment administration, the authors acknowledged.

Disclosures

Funding for the study was provided by the Spanish government.

Ibanez reported support from the European Commission and one co-author reported support from a Madrid governmental program as well. No additional conflicts were reported.

Senussi did not report any conflicts of interest.

Primary Source

Journal of the American College of Cardiology

Source Reference: Clemente-Moragon A, et al "Metoprolol in critically ill patients with COVID-19" J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.07.003.

Secondary Source

Journal of the American College of Cardiology

Source Reference: Senussi MH "Beta blockers in the critically ill" J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.07.006.

https://www.medpagetoday.com/infectiousdisease/covid19/94289