Switching antihypertensive therapy in times of COVID-19: why we should wait for the evidence

This commentary refers to ‘Switching to another antihypertensive effective drug when using ACEIs/ARBs to treat arterial hypertension during COVID-19', by M.M Ciulla, doi:10.1093/eurheartj/ehaa331.

We thank Dr Ciulla for his considerations.¹ Although it might appear tempting to switch antihypertensive therapy to non-renin–angiotensin system (RAS)-inhibitory compounds in otherwise healthy hypertensive individuals, we would like to highlight again the lack of evidence supporting the hypothesis that angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) aggravate the severity or worsen the outcome of COVID-19. As correctly pointed out by Dr Ciulla, ∼50% of patients succumbing to COVID-19 in Italy were taking ACEIs or ARBs. While this in itself does not allow any conclusions on how ACEI or ARB intake relates to outcome, the percentage of patients on ACEI or ARB therapy in China is most probably much lower. Data from the China PEACE Million Persons Project not only show that fewer than one-third of hypertensive patients is indeed receiving antihypertensive medication,² but that the most frequently prescribed single drug is amlodipine and the most frequently prescribed drug class are calcium channel blockers (45.6%). In contrast, prescriptions of ARBs amount to only 21.7% and those of ACEIs to 9.1%.³

On the other hand, there is increasing evidence of activation of the RAS during the course of COVID-19 disease. Specifically, increased levels of angiotensin II were observed in COVID-19-affected individuals, which correlated with viral load and severity of pulmonary disease.⁴ These data are in line with a potential role for RAS activation in lung injury and acute respiratory syndrome (ARDS) from other causes. In fact, use of ACEIs and ARBs was associated with lower pneumonia-associated mortality, as shown in a previous meta-analysis (seven studies for ACEIs, one study for ARBs).⁵ These observations are worrisome in view of a discontinuation of RAS-inhibitory drugs in COVID-19 patients. In addition, similar to the case for ACEIs and ARBs, effects of other antihypertensive therapies—including calcium channel blockers—on the balance of the RAS and outcome of COVID-19 remain to be established. Accordingly, a number of studies are currently planned or have been initiated assessing the effects of RAS inhibition, its discontinuation, alternative antihypertensive drugs (including calcium channel blockers), or administration of Ang1-7 in COVID-19 (e.g. NCT04328012, NCT04312009, NCT04311177, NCT04332666, NCT04329195, NCT04330300, and NCT04322786).⁶ Let’s wait for the evidence, before doing something without knowing exactly what we are doing.

Conflict of interest: none declared