Blood pressure medication and coronavirus: Do ACE inhibitors and ARBs increase the risk of COVID-19?

Analysis of COVID-19 infections has identified that older patients with pre-existing conditions are at higher risk of severe disease. Doctors treating patients further emphasize that people with hypertension and heart disease are at higher risk of complications. This article discusses the relationship between blood pressure medication and coronavirus and what you need to know to protect your overall health.

There are several types of medications used to treat hypertension (high blood pressure). Two of the main classes used to reduce blood pressure are ACE inhibitors and angiotensin receptor blockers (ARBs).  Since the 2003 SARS epidemic, there has been a known link between ACE2 receptors and coronaviruses.

What is ACE2, and how does it relate to coronavirus?

The Angiotensin-converting enzyme 2 (ACE2) is a protein receptor present on the outer surface of cells in the lungs, arteries, heart, kidney, and intestines. Normally, the ACE2 protein plays a vital role in the regulation of blood pressure. Molecular analysis of the virus that caused the SARS disease (called SARS-CoV) identified that the virus uses the ACE2 receptor to attach to and invade cells in humans and bats. ACE2 acts as a host cell receptor for all beta coronaviruses, including the SARS-CoV-2 virus that causes the COVID-19 disease. Experiments in ACE2-deficient cells show that this protein is essential for SARS-CoV-1 and SARS-CoV-2 entry. However, ACE2 receptors are needed to protect the lungs from viral and acid-induced damage. Since ACE2 receptors are present in the lungs, heart, kidney and gut, it helps to explain why COVID-19 affects more organs than flu viruses.

ACE inhibitors and ARBs for the treatment of high blood pressure

ACE inhibitors and ARBs are classes of medication commonly used to treat hypertension (high blood pressure) and reduce the risk of heart disease. They work by reducing blood vessel constriction and inhibit the secretion of aldosterone, which causes hypertension.  ACE inhibitors include drugs such as ramipril (Altace), perindopril (Coversyl) and lisinopril (Zestril). ARBs include drugs such as azilsartan (Edarbi), candesartan (Atacand), irbesartan (Avapro), losartan (Cozaar), olmesartan (Benicar) and valsartan (Diovan). ARBs are often chosen instead of ACE inhibitors because they are less likely to cause side effects such as a dry cough. Early in the pandemic, laboratory studies suggested that these medications might increase the number of ACE2 receptors in the lungs and heart and, in turn, the risk of SARS-CoV-2 infection. However, later clinical studies, including a randomized clinical trial, did not show that continuing these medications worsens COVID-19 outcomes.

This hypothesis, and the associated media coverage, has raised concern among doctors that patients may stop taking their antihypertensive medications out of fear of increase risks with COVID-19. If you are taking an ACE inhibitor or an ARB to manage blood pressure, you should continue your treatment as prescribed. Stopping your antihypertensive treatment will place you at an increased risk for heart attack or stroke and would further increase the risk of COVID-19 complications. Stopping these medications increases blood pressure, increasing your risk of heart and lung failure if you catch the coronavirus, and will not reduce the probability of infection. Furthermore, the ACE2 receptor will always be in your body whether or not you take these medications. In a randomized clinical trial of people hospitalized with COVID-19, stopping ACE inhibitors or ARBs did not improve outcomes compared with continuing them, so you are safer continuing your medication as prescribed.

Talk to your doctor if you are concerned about blood pressure medication and coronavirus

Please do not change your medications or try to get a new drug to protect yourself from coronavirus. The internet and social media are full of inaccurate and misleading publications proclaiming the risks of some medications in relation to the virus, or new “cures” for it. Trust only the press releases of regulatory agencies such as the FDA, Health Canada, European Medicinal Agency (EMA). Please seek the advice of your doctor if you are worried about your chronic conditions or the potential link between blood pressure medication and coronavirus.

It's always a good idea to optimize medications for chronic conditions

In general, if you have a chronic condition such as heart, kidney disease, or diabetes and are taking antihypertensive drugs or experience side effects to medications, you should consider personalized treatment optimization. The Pillcheck Medication Optimization Service includes a genetic test and expert pharmacist review for 355 medications, including the ARBs irbesartan and losartan. Pillcheck assesses your metabolism of many different blood pressure medications, statins and other drugs to help guide safe, effective treatment for personalized to your genetic profile and your cardiovascular conditions.

People who have inherently slower metabolism of irbesartan and losartan have higher blood concentrations of these drugs. With antihypertensive drugs, higher blood levels lead to a more significant reduction in blood pressure, but also increase the risk of side effects such as dizziness, fainting, elevated potassium levels (hyperkalemia), and skin swelling. Pillcheck can assess how your body clears irbesartan and losartan and indicate if you could benefit from a dose reduction or a switch to another type of antihypertensive medication such as calcium channel blockers.

Although Pillcheck results will not provide insights on your risk of COVID-19, this information can help you and your doctor to optimize your medications to improve treatment tolerability and reduce the risk of side effects. Pillcheck can help to optimize drug therapy management of your chronic condition in the long term.

Hoffman et al., SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell (2020)181, 1–10 April 16,
https://www.cell.com/cell/pdf/S0092-8674(20)30229-4.pdf

Haibo Zhang & Andrew Baker, Recombinant human ACE2: acing out angiotensin II in ARDS therapy Critical Care (2017):21, Article number: 305

Batlle D, Wysocki J, Satchell K., Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clin Sci (Lond). 2020 Mar 13;134(5):543-545.

Ankit B. Patel and Ashish Verma, COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. Published online March 24, 2020. doi:10.1001/jama.2020.4812

NEJM Special report: Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19 March 30, 2020 DOI: 10.1056/NEJMsr2005760

Lopes RD, Macedo AVS, de Barros E Silva PGM, et al. Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial. JAMA. 2021;325(3):254-264.

Read also: What is the best blood pressure medication? Part 1 – Types of High Blood Pressure Medications