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Facts or myths: COVID-19 medications related controversies

Could your chronic hypertension medications put you at higher risk for COVID-19?

As data emerged from China on the current pandemic, hypertension and particularly its related medications gained a lot of attention. This started with correspondence in the Lancet but also some media reports addressing this issue and even some calling for patients to consider stopping their hypertension medications.
A particular class of antihypertensives was in the spotlight; angiotensin-converting enzyme inhibitors (ACEI). These are medications that have several indications and proven benefits including in disease states like hypertension and heart failure.

Since the emergence of SARS coronavirus back in 2002 it was identified that the mechanism of cellular entry of the virus is through binding to the ACE2 receptors. These receptors are largely in the lungs and small intestines but have also been reported to be present in the heart.
This fact triggers multiple controversies regarding the interplay of the virus with the cardiovascular system and related pharmacotherapy. The first question of whether patients with chronically up-regulated ACE2 receptors, such as those on ACE inhibitors, are more prone to viral uptake has been a topic of debate. The second being the need to stop, start or continue such medications and their effect on the progression of the virus. Despite the seemingly straightforward implication in enhancing exposure to COVID-19, ACE2 has proved to be a rather complex molecule.

This ACE like enzyme appears to partially reverse the effects of its homolog by reverse converting angiotensin II to angiotensin 1-7. This will theoretically result in lessening the known vasoconstriction and remodeling effects associated with the RAAS and this hypothesis has been utilized to explain the benefits of this strategy in animal models.3,4 In fact, there are currently ongoing randomized controlled trials to explore the potential role of losartan for hospitalized and non-hospitalized COVID-19 patients. Lack of data and randomized trials in humans has led many cardiovascular societies to advise against changing clinical practice with regard to the use of RAAS inhibition for the sole purpose of mitigating the pandemic and continue the standard indication based utilization.7,8,9,10

Previous data from China has indicated that hypertension is common in the adult population. We also know that age is related to worse outcomes with this infection and hypertension is more common in the elderly.

Moreover, the use of the medications of concern here (ACEI) is not very common in hypertensive patients in china and thus we do not expect many of the patients who contracted the virus to have been on these medications. All these facts result in questioning any data linking this pandemic to the use of such medications.

In brief, and until more data is available, do not stop any of your indicated hypertension medications as there is not enough data to implicate these drugs at this time in any risk of contracting the virus or getting sicker if exposed to it.

 

Do we have proven medical therapy for COVID-19?

All the currently suggested medications are rather experimental. Their use is off-label with the exception of hydroxychloroquine which was granted an emergency-use authorization by the FDA.
In fact the only randomized trial we have so far is with the combination antiviral lopinavir/ritonavir and it did not reduce the time to clinical improvement or viral load while resulting in numerically lower mortality.12 Regardless of the weak evidence, it is important to use the current suggested medications in a timely manner that matches their mechanism of action in the cycle of the viral infection.
During the early stages of infection when the virus is multiplying, antiviral medications would be of most benefit. However, as the infection evolves to pulmonary involvement and systemic hyper-inflammation, the host response predominates and anti-inflammatory therapy that targets the cytokines storm would be more useful.11

Should patients who contract the virus be started on blood thinners?

There is emerging data relating the COVID-19 infection to blood clots (venous thromboembolism) and micro emboli. However, the decision to use blood thinners should be based on a series of clinical and laboratory investigations for infected patients who have pneumonia that requires hospital admission.

At this time, all patients who are admitted for treatment and have symptoms should be considered for DVT (deep venous thromboembolism) prophylaxis. This includes using injectable blood thinners such as heparin or low molecular weight heparin (LMWH) to prevent clots.

The decision to use a higher level of anticoagulation with full dose intravenous heparin or therapeutic dose LMWH should follow a specific algorithm that leads to the highest risk patients receiving such therapy. All patients who develop a clot that is confirmed through imaging studies should be placed on full dose blood thinners to resolve the clot and prevent further clotting.

References

  1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens

TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C and Pöhlmann S. SARS-CoV-2 Cell

Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease

Inhibitor. Cell. March 5, 2020. doi: 10.1016/j.cell.2020.02.052. [epub ahead of print].

  1. Tikellis C and Thomas MC. Angiotensin-Converting Enzyme 2 (ACE2) Is a Key

Modulator of the Renin Angiotensin in Health and Disease. Int J Pept. 2012;2012:256294-256294.

  1. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi

H, Crackower MA, Fukamizu A, Hui C-C, Hein L, Uhlig S, Slutsky AS, Jiang C and Penninger

  1. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature.

2005;436:112-116.

  1. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W,

Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky

AS, Liu D, Qin C, Jiang C and Penninger JM. A crucial role of angiotensin converting enzyme 2

(ACE2) in SARS coronavirus–induced lung injury. Nat Med. 2005;11:875-879.

  1. ClinicalTrials.gov. Randomized Controlled Trial of Losartan for Patients With COVID-

19 Not Requiring Hospitalization. Identifier: NCT04311177. March 17, 2020.

https://clinicaltrials.gov/ct2/show/NCT04311177.

  1. ClinicalTrials.gov. Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization. Identifier: NCT04312009. March 17, 2020.
  2. https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang.
  3. https://ish-world.com/news/a/A-statement-from-the-International-Society-of-Hypertension-on- COVID-19/
  4. https://www.eshonline.org/spotlights/esh-statement-on-covid-19/.
  5. https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19
  6. Siddiqu HK, Mehra MR. COVID-19 Illness in Native and Immunosuppressed States: A Clinical-Therapeutic Staging Proposal. Journal of Heart and Lung Transplantation. doi: 10.1016/j.healun.2020.03.012
  7. Cao B, Wang Y, Wen D et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020; (PubMed 32187464) (DOI 10.1056/NEJMoa2001282)

 

 

 

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