A new study supported the absence of a link between hypertension drugs and COVID-19 risk. Researchers found that the medications do not increase the chance of hospitalization and mortality from the novel disease.
The study that examined the association between hypertension drugs and COVID-19 risk was conducted by researchers at Stanford University, a private research university in the US. Their findings revealed that the drugs do not increase the risk of hospitalization, admission to intensive care units (ICUs), and death due to COVID-19. After the examination of numerous medical records, the suspected link was not identified, despite the effect of the drugs in increasing ACE2 – molecules SARS-CoV-2 require to infect human cells. They published their findings in the Journal of Clinical and Translational Science.
The Link Between Hypertension Drugs and COVID-19
Some studies on COVID-19 and its causative pathogen SARS-CoV-2 unveiled how human cells are infected. The virus requires a specific molecule to infect healthy cells. This molecule is called ACE2 and has everything the virus needs to hijack a cell. So, the more ACE2 molecules available, the greater the chance the virus can infect numerous cells. Any mechanism that increases the molecules may potentially enhance the pathogen’s virulence.
From that angle, many experts suggested that medications for high blood pressure or hypertension might raise COVID-19 risk. The risk was correlated to hospitalization, admission to ICUs, and premature death. Certain hypertension drugs could increase the levels of ACE2 molecules to help lower blood pressure. Theoretically, the abundance of the molecules would assist the virus in infecting healthy cells. Thus, those who have been taking such drugs for their hypertension might be at a higher risk of severe COVID-19 outcomes.
According to Statista, a German portal for statistics, about 45.4% of US adults aged 18 years and older had been diagnosed with hypertension, between 2017 and 2018, as of April 2020. Around 22.4% of US adults aged 18 to 39 years, 54.5% of aged 40 to 59 years, and 74.5% of aged 60 years and older suffered from hypertension. Between gender, 51% of US male adults and 39.7% of US female adults suffered from the condition. Across all ages between gender, US male adults had a higher prevalence of hypertension with 31.2% for aged 18 to 39 years, 59.4% for aged 40 to 59 years, and 75.2% for aged 60 years and older, compared to women with prevalence rates of 13% for aged 18 to 39 years, 49.9% for aged 40 to 59 years, and 73.9% for aged 60 years and older.
Based on the 2012 data from the American Heart Association, approximately 12% of US adults aged 20 and older were on angiotensin-converting enzyme inhibitors (ACE-Is), while 5.8% were on angiotensin II receptor blockers (ARBs). Those percentages represented hundreds of thousands of individuals who regularly took the medications. But the percentages have ballooned in later years, which made hypertension drugs one of the most widely used medications in the US alone.
Suspected Link Not Identified as Aggravator of COVID-19 Risk
At Stanford, a group of researchers found evidence that the link between hypertension drugs and COVID-19 risk was not apparent. The relationship did not support the increase in hospitalization, admission to ICUs, and death risk of those who are taking the medications. Even though the drugs would increase ACE2 molecules in the body, the effect could not be exploited by SARS-CoV-2.
"Most clinical trials investigating ACE-I and ARB effects on COVID-19 severity have focused on hospitalized patients and outcomes such as ICU admission, ventilation, and death rates," said Dr. Samuel Rubin, the first author of the study and immunology postdoctoral at Stanford.
Compared to previous studies, their study went beyond hospitalization and outcomes of patients. They also assessed the effects of both ACE-Is and ARBs in raising the chances of outpatients to be hospitalized. Moreover, researchers included patients of all ages and analyzed the results from both drug classes from each other. This gave them a better view of the statistical evidence of the suspected link.
In the study, researchers collected the medical records of 1,023 patients diagnosed with COVID-19 at Stanford Hospital and Clinics, through April 8, 2020, after receiving approval from the review board. The patients were confirmed with COVID-19 by RT-PCR tests – the gold standard in COVID-19 testing. The cohort was comprised of both inpatients and outpatients, but the primary reason for hospital admission of 123 patients was COVID-19.
Twelve other patients were admitted for other primary causes related to COVID-19, two for altered mental status (AMS), one for AMS secondary to metabolic or septic encephalopathy, one for AMS-related hypercapnia, one for anti-N-methyl-D-aspartate receptor autoimmune encephalitis, one for hyponatremia, one for pancytopenia, one for C-section delivery, one for hip fracture, one for urinary tract infection, one for acute cholecystitis, and one for fever. As detailed by the study, many inpatients were admitted due to preexisting medical conditions, not just because of COVID-19.
From April 8, 2020, all patients in the study were followed until April 22, 2020, or for a total of 14 days. The youngest patient was aged six months while the oldest was 100 years of age, which depicted the diversity in age. The most common preexisting medical conditions among patients were hypertension at 29.1% and diabetes at 16%. Out of 29.1% of patients with hypertension, 30% of them were on ACE-Is and 30.6% were on ARBs.
Results showed that neither ACE-Is nor ARBs caused an increase in the risk of hospitalization, ICU admission, and death of COVID-19 patients. The comparison between the study cohorts and charted past medical history even showed a decrease in the risk. The odds for patients on ACE-Is to be hospitalized were 0.43 lower, while the odds for patients on ARBs to be hospitalized were 0.39 lower. Compared to patients who were not on either ACE-Is or ARBs, the odds of those on ARBs to be hospitalized was 0.09 lower.
Although the lower odds might not be statistically high, the numbers highlighted that the use of either ACE-Is or ARBs do not exacerbate the risk of adverse outcomes from COVID-19. If the numbers would mean something, the medications might help reduce the chance of adverse outcomes from the disease. The improvement in COVID-19 outcomes could be correlated to the drugs’ ability to regulate blood pressure, which helps prevent major organs from quickly declining during infection.
The reason why ACE2 molecules exacerbated by drugs are not exploitable has been their position. Most of the molecules are likely floating freely in the bloodstream. The virus needs the molecules on the surfaces of host cells, and only cells that produce the molecules will likely have them on the surface. Also, the free-floating ACE2 molecules may serve as decoys for the virus to attach to.