A new multicenter study that recently appeared on the medRxiv* preprint server in November 2020 has found a lower or equal risk of fatal coronavirus disease 2019 (COVID-19) in hypertensive patients, depending on the type of medication they are on.
This finding confirms earlier recommendations that antihypertensives should be continued in these patients before and during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral agent that causes COVID-19.
The evidence as of now indicates that advancing age and the presence of cardiovascular disease both increase the risk of severe illness in patients with COVID-19.
The virus engages target host cells via its receptor-binding domain (RBD) on the S1 subunit of its spike protein, which attaches to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell. The ACE2 molecule, however, is part of the renin-angiotensin-aldosterone system (RAAS), which modulates vascular tone and cardiovascular activity.
The question is whether this system plays any part in the disease process underlying COVID-19, and whether antihypertensive drugs that act on the RAAS would affect this system in any way. Such drugs may be able to inhibit the system to cause a higher level of ACE2 expression.
Some researchers postulate that RAAS inhibition may be protective against acute lung injury by reversing the build-up of angiotensin II caused by this pathological state. Until strong evidence of any adverse effect of such drugs is available, therefore, most medical associations have recommended that patients continue to take them as prescribed. Available literature shows no risk of a poor outcome in these patients if they contract the infection.
Since these studies were mostly retrospective, the current paper describes an attempt to add more data by a multicenter retrospective cohort study in France. It included almost 3,700 patients at 39 hospitals in Greater Paris, all adults with one or more positive viral RNA tests, by real-time reverse transcriptase-polymerase chain reaction (RT PCR), and who had been hospitalized between February 1 and May 15, 2020. All were followed up for 30 days or more.
The median patient age was 75 years, and 57% were male. Over 55% were on RAAS inhibitors, 44% were taking calcium channel blockers (CCBs), around 38% were on beta-blockers, while a small percentage, less than 5%, were using central sympathetic inhibitors. About a quarter were not on any antihypertensive medication.
In this group, there were around 850 deaths, accounting for a quarter of the group, from all causes, within the 30-day follow-up period. Most of the deaths occurred among the older patients, and more were male, as well as having chronic conditions at a higher frequency, except for obesity and respiratory disease.
When the patients who were taking RAAS inhibitors were further classified, it was found that about 27% and 31% used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), respectively. The adjusted odds of death within this group in this period were 17% lower for those on CCBs, 20% lower for those on beta-blockers, but unchanged for ARB users or ACEI users, relative to those who were not on these medications.
The current study is among the largest in hypertensives with COVID-19. Its findings rule out any link between the use of antihypertensive drugs, even those which interfere with the RAAS, and a higher risk of death in hospital. Moreover, the study supports a protective effect for these drugs in these patients.
Since hypertension by itself is a risk factor for a poor outcome in COVID-19, the benefit predicted with these drugs is non-negligible. The mechanism by which they confer protection is unclear. It might be that beta-blockers inhibit potentially harmful sympathetic activation due to the virally-induced cytokine storm, and some data on porcine coronavirus infection suggests that CCB may inhibit infection as well as disruption of calcium homeostasis.
Further studies to bolster this conclusion may be needed, but the findings are encouraging, in that there is no obvious connection between the use of drugs that act on the RAAS and a higher risk of death in hospitalized patients suffering from COVID-19 and hypertension. This would support the recommendation that patients with hypertension continue to use their accustomed medication, including ARBs and ACEIs.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.