Summary of Medscape's review on Angiotensin Drugs
“Do not change medication based on no evidence.” — Prof. Franz Messerli
In wake of growing reports about the adverse effects of a pair of drugs used to treat diabetes and hypertension (high blood pressure), Medscape has reviewed the evidence and consulted a number of cardiovascular experts for their opinion. Below are my 10 notes from their article:
- The drugs in question are angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
- ACE inhibitors are used to reduce hypertension. Hypertension is induced by muscles constricting the blood vessels they surround, which in turn decreases the diametre of vessels and in turn increases blood pressure. Angiotensin II causes muscles to contract as it circulates in the blood and can, therefore, come into contact with muscles.
- ARBs are used to reduce hypertension. These drugs compete with angiotensin II to block the action of angiotensin II in the blood so muscles don’t contract, and in turn, decrease blood pressure.
- It’s been found that as a consequence of using ACE inhibitors and ARBs, there’s an increased expression of ACE2 receptors on the heart, lungs and gut.
- ACE2 receptors are believed to be the entry point for the glycoprotein that binds with cells to then deliver COVID-19 into the nucleus.
- Several studies from China indicated a high incidence of cardiovascular comorbidities in COVID-19 patients. However, this could be accounted for by confounding as patients with cardiovascular conditions are likely to be older and have other comorbidities.
- Yet, as there’s an increase in ACE2 receptors, the hypothesis is that this increases susceptibility to COVID-19.
- Alternatively, there are some suggestions that an increase in ACE2 brings positive effects. ARBs increase the availability of angiotensin II by competing for the same receptor, and this can in turn increase binding of angiotensin to the catalytic domain of ACE2, creating a structural change that’s unfavourable for COVID-19.
- There’s a proposal to use ARBs as a treatment for patients with COVID-19 to reduce the risk or severity of viral pneumonia. When ACE2 binds to the spike protein of COVID-19, there’s downregulation of ACE2 which results in excessive production of angiotensin II and less ACE2 to convert into the vasodilator angiotensin 1–7 which causes lung injury. Therefore, it’s being suggested that higher ACE2 expression with ARBs protects patients against acute lung injury.
- Competing evidence from animal models that suggests ACE inhibitors and ARBs can dually be helpful/harmful to COVID-19 patients is not complemented with clinical data. While the exact role of using ACE inhibitors and ARBs for treating COVID-19 patients is unclear, for patients with diabetes or hypertension that stop using these drugs the consequence is unanimously understood by the medical community. For instance, patients with advanced kidney disease that stop taking ACE inhibitors or ARBs have a 39% increase in mortality rates over 2 years. As Prof. Franz Messerli declares, ‘do not change medication based on no evidence’, and consequently, with such uncertainty surrounding the usage of ACE inhibitors and ARBs, the recommendation is to continue using these drugs and that there has yet to be any proven consequences with using these drugs in clinical settings.