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The epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. In this scenario, decisions on preventive, symptomatic and potentially life-saving treatments both in the general population and in patients with novel coronavirus disease 2019 (COVID-19) must be based on sound scientific evidence. Controversial hypotheses about the possible detrimental/ protective effects of antihypertensive drugs acting on the renin–angiotensin–aldosterone system (RAAS) in patients with COVID-19 have been postulated in several editorials and letters [1–4]. Through the regulation of vascular peripheral resistance and, potentially, of blood volume, the RAAS plays a crucial role in the etiology of hypertension. Moreover, this system promotes atherogenic processes by increasing oxidative stress, stimulating vascular muscle and monocyte proliferation. Based on their biological target, drugs inhibiting the RAAS may be distinguished as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and direct renin inhibitors (DRIs). ACEIs enact their blood pressure-lowering effects by blocking the peptidyldipeptidase that hydrolyzes angiotensin I (A-I) to angiotensin II (A-II). In addition, it inactivates bradykinin, a vasodilating peptide promoting the release of nitrogen monoxide and prostacyclin. ARBs have no effect on bradykinin metabolism and block the effects of A-II more selectively than ACEIs. In detail, ARBs determine their antihypertensive effect by preventing the binding of A-II to the A-II receptor type 1 (AT1). Finally, DRIs exert blood pressure-lowering effects by decreasing plasma renin activity and inhibiting the conversion of angiotensinogen to A-I [5]. In vitro studies demonstrated that ACEIs and ARBs can significantly increase the expression and activity of angiotensin-conversion enzyme 2 (ACE2), highly expressed in the heart and lungs [6]. Coincidentally, ACE2 is the receptor-binding site for the spike protein of SARS-CoV-2 at the target cell [7]. Hence, Fang et al. [4] recently hypothesized in The Lancet Respiratory Medicine that patients with cardiac diseases, hypertension, or diabetes mellitus treated with ACE2-increasing drugs might be at higher risk for severe SARS-CoV-2 infection. Accordingly, the authors suggested that calcium channel blockers (CCBs) may be a more suitable alternative antihypertensive treatment than ARBs/ ACEIs because of their lack of increased ACE2 expression or activity. On the other hand, recently published commentaries outlined the mechanisms by which RAAS inhibitors may be beneficial in patients with COVID-19 and discussed the unclear effects of these drugs on ACE2 levels and activity in humans, recommending against the suspension or withdrawal of RAAS blockers [8, 9]. We present here our contribution to the scientific debate, highlighting the importance of continuing ACEI/ARB treatments and reporting several arguments against switching from ACEIs or ARBs to other antihypertensive drugs and specifically to CCBs. Italian Society of Pharmacology members are listed in acknowlegements.

drug safety

Should Patients Receiving ACE Inhibitors or Angiotensin Receptor Blockers be Switched to Other Antihypertensive Drugs to Prevent or Improve Prognosis of Novel Coronavirus Disease 2019 (COVID-19)?