About Sartans: An Overview with Consideration of Their Position in the Current Coronavirus Situation

Action of Sartans

The mechanism of action involves antagonism of the AT₁ receptors for angiotensin II. Their advantage over ACEi is a more comprehensive inhibition of angiotensin II and the fact that they do not interfere with the catabolism of other neuropeptides, which at higher concentrations can cause a dry cough.

There are differences among sartans primarily in terms of duration of action, receptor affinity, and inhibition method. These differences can be advantageous to consider when selecting a medication. Losartan has the shortest half-life, while telmisartan is among the longest-acting. The highest receptor affinity has been demonstrated in azilsartan and telmisartan.

Indications

In addition to treating arterial hypertension, sartans can also be used for other indications. They are considered in cases of left ventricular hypertrophy, congestive heart failure, and ischemic heart disease, diabetic nephropathy, and renal insufficiency. In type 1 diabetic patients, sartans have been shown to reduce proteinuria. If angioedema or hyperkalemia develops when initiating ACEi, sartans cannot be used as an alternative.

Beneficial effects of sartans include mitigating erectile dysfunction or preventing its development during hypertension treatment. The potential impact of sartans on reducing migraine frequency is also being investigated. Other positive effects include the uricosuric effect of losartan.

Given the trend towards combination hypertension therapy, combining sartans with a dihydropyridine calcium channel blocker is advisable, having the most favorable safety profile.

Side Effects and Contraindications

Treatment with sartans can lead to hyperkalemia. Therefore, regular monitoring of potassium, urea, and creatinine levels is recommended. Another side effect can be excessive blood pressure reduction and orthostatic hypotension. To avoid first-dose hypotension, careful dose titration is advisable.

Due to their teratogenicity, sartans are contraindicated in women of childbearing age. Other contraindications include intravascular volume depletion due to bleeding, diarrhea, or vomiting, and bilateral renal artery stenosis.

Recommendations for Patients with COVID-19 Infection

In the context of the COVID-19 pandemic, the safety of sartans and ACEi has been frequently discussed. Questions arise regarding the ACE2 surface receptors in the lungs and intestines, which are entry points for SARS-CoV-2. The initially presumed adverse effect of ACEi and ARBs has not been definitively confirmed. Conversely, a recently published Chinese study describes cases of hospitalized patients who were using ACEi/ARBs, showing an overall lower mortality risk compared to those not treated with these drugs. Studies worldwide are ongoing on this topic, and conclusions are not yet definitive.

According to recent recommendations, it remains advisable not to change the treatment of patients on ACEi or sartans. For patients who contract COVID-19, their status should be individually assessed before adjusting their treatment. Although there are indications that mortality rates may be higher among patients treated with ACEi than with sartans, these studies are not yet extensive enough and do not consider comorbidities, age, and other factors.

Given that the therapeutic effects of ACEi and sartans are comparable, but the safety profile of sartans is more favorable, sartans may represent a more suitable alternative for treating hypertension in patients with COVID-19 at risk of severe disease.

(sobo)

Sources:
1. Pardini C. Joint statement issued addressing concerns over COVID-19 and ACE inhibitor, ARB use. Cardiology Advisor, 2020 Mar 24. Available at: www.thecardiologyadvisor.com/general-cardiology/joint-statement-issued-addressing-concerns-over-covid-19-and-ace-inhibitor-arb-use
2. Sanchis-Gomar F., Lavie C. J., Perez-Quilis C. et al., Angiotensin-converting enzyme 2 and antihypertensives (angiotensin receptor blockers and angiotensin-converting enzyme inhibitors) in coronavirus disease 2019. Mayo Clin Proc 2020 Apr 4, doi: 10.1016/j.mayocp.2020.03.026 [Epub ahead of print].
3. Murray S. New evidence concerning safety of ACE inhibitors, ARBs in COVID-19. PharmacyTimes, 2020 Apr 28. Available at: www.pharmacytimes.com/news/new-evidence-concerning-safety-of-ace-inhibitors-arbs-in-covid-19
4. Widimský J. Doporučení pro léčbu a diagnostiku arteriální hypertenze ČSH 2017. Česká společnost pro hypertenzi. Available at: www.hypertension.cz/sqlcache/widimsky-1-hypertenze-kv-prevence-2018.pdf