Antihypertensive Drugs Not Associated With Greater COVID-19 Risk, Severity

Patients taking common hypertensive medications were not found to be at higher risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or to be more likely to have severe complications from coronavirus disease 2019 (COVID-19), according to an article published in the New England Journal of Medicine.¹

SARS-CoV enters into cells through the binding of its S1 domain to angiotensin-converting enzyme 2 (ACE2) on the cell surface.² Inhibitors of the renin-angiotensin-aldosterone system (RAAS), which includes ACE2, may upregulate membrane expression of ACE2, thus promoting the binding of SARS-CoV-2 to cells of the respiratory epithelium. This has led to concerns regarding the use of RAAS inhibitors during the COVID-19 pandemic. In addition, patients with vs without hypertension and COVID-19 may be at greater risk for death and severe complications from the disease.³

This observational study included patients admitted to New York University (NYU) Langone Health system with COVID-19 that was confirmed between March 1 and April 15, 2020. Medical records of patients were reviewed to identify those with a diagnosis of a condition treated with RAAS inhibitors (eg, hypertension, myocardial infarction, or heart failure) as well as the use of these prescriptions in the preceding 18 months. In this cohort, the hypertensive medications were: ACE inhibitors, angiotensin-receptor blockers (ARBs; eg, sacubitril-valsartan), ACE inhibitor or ARB, calcium-channel blockers, β-blockers, and thiazide diuretics.

Of the 5894 patients who tested positive for COVID-19 during this time period, 17.0% had severe manifestations of the disease (ie, requiring admission to an intensive care unit or ventilation, or resulting in death). Among the patients who had hypertension (n=4357; median age, 64 years; whites, 48.2%), 59.1% tested positive for COVID-19 vs 40.9% who tested negative.

In an analysis of matched patients with hypertension, the percentage of patients with COVID-19 was comparable in those treated with 1 of the 5 types of hypertensive medication/combinations examined vs no medication (as indicated by absolute differences <10 percentage points). Results were similar in an analysis of all matched patients. All matched patients treated with β-blockers vs no hypertensive medication had a marginally lower risk for infection with COVID-19 (median difference, −3.8 percentage points; 95% CI, −7.1 to −0.4).

Of the 2573 patients with hypertension and COVID-19, 24.6% had a severe manifestation of the disease. In a propensity score matching analysis, the percentages of patients with hypertension (or all patients) with severe COVID-19 were similar whether they were treated with any of the 5 types of hypertensive medication or had not taken any medication. COVID severity was higher — although not significantly — in patients treated with calcium channel blockers vs no medication (median difference, 4.4 percentage points; 95% CI, 0.5-8.2), compared with all other hypertensive drugs.

Study limitations include the heterogeneity in diagnostic tests used, and a possible overestimation of the percentage of severe cases.

“Our findings may help to allay concerns on the part of patients and providers regarding the continued use of these agents in patients undergoing testing or receiving treatment for COVID-19,” concluded the study authors.

We spoke with Harmony R. Reynolds, MD, director of the Sarah Ross Soter Center for Women’s Cardiovascular Research at NYU Langone Health, and lead author of the study.

On March 17, 2020, the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America issued a joint statement in which they encouraged studies examining COVID-19 outcomes in patients taking hypertensive medications. Will findings from this and other studies allow these societies to now recommend this patient population be maintained on their hypertensive drug regimen?

Dr Reynolds: I do believe our results support a statement from the professional societies recommending that patients be continued on their antihypertensive drugs, including ACE inhibitors and ARBs.

In another study,⁴ patients with COVID-19 taking ACE inhibitors vs no medication had a better survival rate. Although this finding may be due to confounding factors, is this something that you deem worthwhile to investigate?

Dr Reynolds: We did not find a signal of a survival difference related to the use of ACE inhibitors. I look forward to seeing more related data in the future to find out if ACE inhibitors could in fact be protective.

References

1. Reynolds HR, Adhikari S, Pulgarin C, et al. Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19 [published May 1, 2020]. N Engl J Med. doi:10.1056/NEJMoa2008975
2. Li W, Moore M, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426;450-454.
3. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-1720.
4. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in Covid-19 published May 1, 2020]. N Engl J Med. doi:10.1056/NEJMoa2007621