A study has found that high blood pressure medications are safe for patients with COVID-19 disease. Launched in response to a 17 March joint statement issued by the American Heart Association, the American College of Cardiology, and the Heart Failure Society of America. It urgently called for research to answer a question raised by past studies: do high blood pressure (antihypertensive) drugs worsen COVID-19 patient outcomes?
Led by researchers from NYU Grossman School of Medicine, the study found no links between treatment with four drug classes – angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta blockers, or calcium channel blockers – and increased likelihood of a positive test for COVID-19. Further, the study found no substantial increase in risk for more severe illness (intensive care, use of a ventilator, or death) with any of the treatments in patients with the pandemic virus.
"With nearly half of American adults having high blood pressure, and heart disease patients more vulnerable to COVID-19, understanding the relationship between these commonly used medications and COVID-19 was a critical public health concern," says lead investigator Dr Harmony Reynolds, associate director of the Cardiovascular Clinical Research Centre at NYU Langone Health. "Our findings should reassure the medical community and patients about the continued use of these commonly prescribed medications, which prevent potentially severe heart events in their own right."
For the study, the researchers identified patients in the NYU Langone Health electronic health record with COVID-19 test results. For each identified patient with COVID-19 test results, the team discretely extracted medical history needed for the analysis, which compared treated and untreated patients.
"Before our study, there were no experimental or clinical data demonstrating the consequences of using these medications one way or the other in people at risk for COVID-19," says senior study author Dr Judith Hochman, the Harold Snyder Family professor of medicine and senior associate dean for clinical sciences at NYU Langone Health. "In terms of next steps, our plan is to use similar approaches to investigate other medications and their relationship to COVID-19 illness."
The study revolves around drugs that act on the renin-angiotensin-aldosterone hormonal system, which influences blood pressure. Central to this system is the signalling protein angiotensin II, levels of which are controlled by angiotensin-converting enzyme (ACE), say the authors. Angiotensin II narrows blood vessels to increase blood pressure, and the study drugs counter that, either by blocking ACE-induced increases in angiotensin II, or the ability of ACE to interact with its receptor signalling partners on cells.
According to the researchers, one version of ACE, angiotensin converting enzyme 2 (ACE2), is present in the outer membrane of lung cells. SARS-CoV-2, the current pandemic virus, has been shown to connect to ACE2 on lung cells, a first step toward viral infection. This led to concern in the field that ACE inhibitors and ARBs might increase or worsen COVID-19 infection. Past studies in animal models had suggested that ACE inhibitors and ARBs increase ACE2 production in other organs, but how they related to ACE2 levels in the lungs was not known.
On the other hand, ACE inhibitors and ARBs had been shown elsewhere to reduce lung injury in certain viral pneumonias, creating speculation that they might be helpful. The new study was designed to address these contradictions.
Along with Reynolds and Hochman, authors of the study from NYU Grossman School of Medicine were Andrea Troxel, director of the division of biostatistics; Samrachana Adhikari, Claudia Pulgarin, Eduardo Iturrate, Stephen Johnson, Anais Hausvater, Jonathan Newman, Jeffrey Berger, Sripal Bangalore, Stuart Katz, Glenn Fishman, Dennis Kunichoff, Yu Chen, and Gbenga Ogedegbe.
Abstract
Background: There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).
Methods: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference.
Results: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.
Conclusions: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.
Authors
Harmony R Reynolds, Samrachana Adhikari, Claudia Pulgarin, Andrea B Troxel, Eduardo Iturrate, Stephen B Johnson, Anaïs Hausvater, Jonathan D Newman, Jeffrey S Berger, Sripal Bangalore, Stuart D Katz, Glenn I Fishman, Dennis Kunichoff, Yu Chen, Gbenga Ogedegbe, Judith S Hochman
[link url="https://nyulangone.org/news/study-finds-high-blood-pressure-medications-safe-patients-covid-19-disease"]NYU Langone Health/NYU School of Medicine material[/link]
[link url="https://www.nejm.org/doi/10.1056/NEJMoa2008975"]NEJM abstract[/link]