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Best Practices for Treating Comorbidities in Patients with COVID-19 

Apr 7, 2020
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Mia Flowers, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy

Patients with diabetes and hypertension may be affected differently in COVID-19 infections. 

Currently, COVID-19, also known as coronavirus disease 2019 or coronavirus for short, is causing a worldwide uproar due to a plethora of unanswered questions. Recent studies in China have revealed some information regarding comorbidities associated with the virus. Studies show that patients suffering fatalities from the pandemic had previous medical histories of cerebrovascular diseases, cardiovascular diseases including hypertension and coronary artery diseases, and diabetes mellitus. Angiotensin-converting enzyme (ACE) inhibitors were a common treatment found in three studies involving patients with these diseases that did not survive the coronavirus. There has not been much focus on the treatment regimens of these disease states within the population diagnosed with COVID-19.  

This form of the coronavirus is a severe acute respiratory syndrome (SARS) that binds to its target cells via a mechanism involving the angiotensin-converting enzyme 2 (ACE 2) found in the blood vessels, lungs, intestines, and kidneys. Patients with diabetes, type 1 or 2, who are taking ACE inhibitors or angiotensin ii receptor blockers (ARBs) have an increase in the expression of ACE 2, which is thought to aid in the spread of the virus throughout the body. ACE inhibitors and ARBs are most commonly used in patients with hypertension and heart failure. The diabetes treatment thiazolidinediones (pioglitazone and rosiglitazone) and non-steroidal anti-inflammatory drug (NSAID) ibuprofen have the capability of increasing ACE 2. Also, the expression of ACE 2 is increased in patients with diabetes. Thus, researchers have hypothesized that treatment with ACE inhibitors and ARBs can stimulate the development of a fatal and severe version of COVID-19 infections within patients with diabetes and hypertension.  

Another facet of this problem is the role of genetics. Polymorphisms of ACE 2 linked to chronic diseases like hypertension, diabetes mellitus, and cerebral vascular accidents could genetically predispose people to increase the risk of developing the coronavirus. Further investigation would be needed to confirm these findings in addition to determining therapeutic substitutes and whether patients using ACE inhibitors or ARBs have worse outcomes that would warrant putting them at risk for other adverse events such as an increase in cardiovascular events, heart failure symptoms or renal impairment. An alternative antihypertensive treatment to ACE inhibitors or ARBs recommended by this author is calcium channel blockers which have not been found to increase the incidence of angiotensin-converting enzyme 2 expressions.  

Other healthcare care experts argue that drugs could offer protection by increasing the amount of soluble ACE 2 in the body. The soluble version of the enzyme would serve as a decoy to the coronavirus in that the binding of the virus to these cells could prevent replication. However, this is theoretical and no reports have yet discerned whether the soluble ACE 2 is placed in an aqueous layer that would inhibit the virus’ penetration of the lungs. Also, other studies claim that angiotensin ii is required for scarring of the lungs. Fibrosis of the lungs has been a significant consequence of COVID-19 seen in most of the survivors in severe cases. ACE 2 is the enzyme responsible for the breakdown of angiotensin II which could aid in the prevention of lung fibrosis. ACE inhibitors and ARBs could be useful in this sense. On March 17, 2020, the American College of Cardiology, American Heart Association, and the Heart Failure Society of America released statements recommending that ACE inhibitors and ARBS be continued in patients who were previously prescribed those therapies for ischemic heart disease, heart failure, and hypertension. While individualized treatment is encouraged, there is insufficient evidence to support the discontinuation of the specified antihypertensive medications. It also recommended for healthcare providers to stay up-to-date on the latest research regarding the virus. Some may argue that the risk of worsening cardiovascular and renal complications in patients with chronic disease is not worth the possibility that these drugs may contribute to the replication of COVID-19 within the body.  

Studies in Italy, who lead the world in fatalities from the coronavirus at time of writing, have revealed findings that are in agreeance with age and cardiovascular comorbidities increasing the risk of severity of the infection. In those who have passed in Italy, coronary artery disease, diabetes, and hypertension have the highest incidence. However, only age was found to be an independent risk factor in a study for a predictor of mortalities associated with COVID-19. The PEACE Million Persons Project in China studied 1.7 million patients and less than 10% could reach their therapeutic targets for 30% who were diagnosed and treated for hypertension. Over 50% of those subjects were treated with CCBs and less than 30% utilized ACE inhibitors or ARBs.  The CCBs ultimately have not been found to offer the same evidence-based clinical benefits and could leave patients more vulnerable to chronic illness. These statements all suggest that further comprehensive studies involving the treatment of these disease states during COVID-19 infection are necessary.  

Practice Pearls: 

  • Discussion of whether antihypertensives may be of harm or help to patients with COVID-19 is a current hot button during this pandemic.  
  • The ACC/AHA recommends keeping patients on ACE inhibitors and ARBS if they are not treatment naïve. 
  • Further studies are needed to determine the best course of action for this patient population.  

 

Fang, Lei, et al. “Are Patients with Hypertension and Diabetes Mellitus at Increased  Risk for COVID-19 Infection?” The Lancet Respiratory Medicine, Elsevier, Mar. 2020,  doi:10.1016/S2213-2600(20)30116-8. 

Zhao, Binghao, et al. “Association of Magnesium Intake with Type 2 Diabetes and Total  Stroke: An Updated Systematic Review and Meta-Analysis.” BMJ Open, vol. 10, no. 3,  Mar. 2020, p. e032240, doi:10.1136/bmjopen-2019-032240. 

 

Mia Flowers, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy 

 

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