Do antihypertensive drugs raise odds of COVID-19 diagnosis, death?

Antihypertensive therapy (AHT) may be used safely during the COVID-19 pandemic, as no evidence suggest that it can increase the risk of SARS-CoV-2 infection or death, according to a UK study. In addition, most classes of antihypertensives are negatively associated with COVID-19 diagnosis.

“There was evidence that, after adjusting for covariates including blood pressure, several classes of AHT might be associated with lower risk of a clinical COVID-19 diagnosis, but this pattern of association was not apparent for COVID-19 mortality,” the researchers said.

“While this might be interpreted as evidence of a protective effect, in this observational study it is not possible to exclude the possibility that this pattern of association may be caused by bias,” they added.

In this population-based case-control study, the researchers analysed a total of 16,866 COVID-19 patients and 70,137 matched controls from the UK Clinical Practice Research Datalink. They evaluated all-cause mortality among cases.

Exposures were as follows: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, calcium-channel blockers (CCB), thiazide diuretics (TZD) and other antihypertensive agents. The researchers adjusted analyses for covariates and consultation frequency.

ACEIs correlated with a lower likelihood of COVID-19 diagnosis (adjusted odds ratio [aOR], 0.82, 95 percent confidence interval [CI], 0.77‒0.88), as did ARBs (aOR, 0.87, 95 percent CI, 0.80‒0.95), with only a slight decrease after adjusting for consultation frequency. [Br J Clin Pharmacol 2021;87:4598-4607]

The odds of COVID-19 diagnosis were also lower with CCBs and TZDs, whereas the increased chances of such infection for beta-blockers (aOR, 1.19, 95 percent CI, 1.12‒1.26) weakened following adjustment for consultation frequency (aOR, 1.01, 95 percent CI, 0.95‒1.08).

Moreover, patients treated with ACEIs or ARBs (aOR, 1.00, 95 percent CI, 0.83‒1.20) had mortality odds comparable to those treated with beta-blockers, CCBs, TZDs, or other antihypertensives or those not on any AHT (aOR, 0.99, 95 percent CI, 0.83‒1.18).

“While previous studies have largely evaluated drugs acting on the renin-angiotensin-aldosterone system (RAAS), the study found no evidence that any class of AHT might be associated with greater risk of COVID-19 diagnosis or mortality,” the researchers said.

Several systematic reviews found no evidence for worse COVID-19 outcomes in patients treated with these medications. [Pharmacol Res 2020;158:104927; Hypertension 2020;76:1563-1571; BMJ Open 2020;10:e040644; Am J Cardiovasc Drugs 2020;20:571-590; Thorax 2021;76:479-486; Int J Cardiol 2020;321:150-154]

However, some studies indicated that ACEIs and ARBs were associated with reduced risk of indicators of severe COVID-19 disease, but systematic reviews stressed the limitations of evidence presented thus far. [J Med Virol 2021;93:1370-1377; Heart 2020;106:1503-1511]

“ACEIs and ARBs modulate the RAAS, and treatment with ACEIs and ARBs may enhance angiotensin-converting enzyme 2 (ACE2) activity, thereby increasing SARS-CoV-2 susceptibility and COVID-19 severity,” the researchers said. [JAMA Cardiol 2020;5:745-747; Sci China Life Sci 2020;63:364-374]

“Conversely, increased ACE2 might have a protective effect by competitive inhibition of SARS-CoV-2 entry into the respiratory epithelium or via negative regulation of the RAAS for anti-inflammatory, antioxidative and vasodilatory effects,” they added. [Clin Sci 2020;134:543-545]