Which drugs work similarly to aprocitentan?

Aprocitentan (aprocitentan) is a new type of endothelin receptor antagonist, mainly used to treat cardiovascular-related diseases such as refractory hypertension. Its mechanism of action is to exert its antihypertensive effect by antagonizing the activation of ETA and ETB receptors by endothelin-1 (ET-1). There are many drugs that have a similar mechanism of action to aprecitentan and can also be used to control blood pressure or improve cardiovascular disease, including other endothelin receptor antagonists, calcium channel blockers, RAAS system inhibitors, etc. The following will analyze from different categories, representative drugs with similar functions to aprecitentan and their differences.

1. Similar drugs: other endothelin receptor antagonists

Endothelin Receptor Antagonists, same as aprecitentan (Endothelin Receptor Antagonists, Drugs in the ERAs category include bosentan, ambrisentan, and macitentan. These drugs are mainly used to treat pulmonary arterial hypertension (PAH). Their mechanism is to block endothelin receptors and reduce vasoconstriction and cell proliferation.

1.Bosentan (Bosentan): is the earliest approved ERAThe drug can double block ETA and ETB receptors, and is suitable for improving symptoms such as decreased exercise capacity caused by pulmonary hypertension. However, bosentan is associated with liver function damage, so liver function needs to be monitored regularly.

2.Ambrisentan (Ambrisentan): Mainly selectively acts on ETA receptors, reducing pulmonary vascular resistance while having low liver toxicity. Because it less affects ETB receptors, its direct effect on blood pressure is relatively mild and is more suitable for long-term use.

3.Macitentan (Macitentan): It has stronger receptor binding ability and long-lasting efficacy, while reducing the incidence of adverse reactions. It has been widely used in the treatment of PAH and is also considered to have potential application value in refractory hypertension.

As an improved dual-receptor blocking drug, the main advantage of aprecitentan is its ability to treat ETA and ETB receptors have high affinity and long-lasting blocking ability, and have achieved clinical breakthroughs in hypertension indications. Compared with the above ERA, it is not only suitable for PAH, but also more suitable for resistant hypertension, showing new clinical value.

2. RAASSystem inhibitors

Although their mechanisms are different, angiotensin-converting enzyme inhibitors (ACEI) and angiotensinII receptor antagonists (ARB) also play similar roles in the treatment of hypertension, especially in dilating blood vessels and relieving myocardial burden.

1.Ramipril, benazepril (ACEI class): These drugs block the conversion of angiotensinI to angiotensinII, thereby reducing the production of vasoconstrictor substances, thereby lowering blood pressure. ACEI drugs can also increase the content of bradykinin and have the effect of relaxing blood vessels.

2.Valsartan, irbesartan (ARB type): different from ACEI ,ARBdirectly blocks the binding of angiotensinII to its receptor, which is more targeted and has relatively fewer side effects (such as dry cough). This type of drug can be used in combination with aprecitentan to improve the antihypertensive effect.

AlthoughRAAS system drugs do not act on the endothelin pathway, they also improve blood pressure control by intervening in the vasoconstriction pathway and can be used as an important auxiliary in the treatment of refractory hypertension in clinical practice.

3. Calcium channel blockers (CCB)

Calcium channel blockers (CCB) such as amlodipine and nifedipine inhibit the influx of calcium ions into vascular smooth muscle cells, dilating blood vessels and achieving antihypertensive effects. These drugs are mostly used to treat mild to moderate hypertension.

AlthoughCCBThe target of action is different from that of aprecitentan, but it has certain similarities in dilating blood vessels. Especially in the treatment of refractory hypertension, CCBs are often used in combination with endothelin receptor antagonists to enhance the antihypertensive effect and reduce single-drug resistance.

4. Diuretics andβ-blockers

Refractory hypertension in some patients is related to fluid retention or sympathetic nerve overexcitability. At this time, thiazide diuretics (such as hydrochlorothiazide) or β-blockers (such as metoprolol) may also have complementary effects with aprecitentan to form a combined antihypertensive treatment.

It should be noted that aprecitentan was developed specifically for patients with refractory hypertension who are poorly controlled by traditional drugs, so it shows stronger antihypertensive potential in people who have failed previous treatments.

In general, aprecitentan, as an endothelin receptor antagonist, has not yet been marketed in China, but it has important potential in the treatment of refractory hypertension. Its mechanism is similar to ERA drugs such as bosentan, macitentan, and ambrisentan, but it focuses more on indications for hypertension. At the same time, in clinical programs, it is often used in combination with RAAS inhibitors, CCB, etc. to form a multi-mechanism intervention treatment model. As follow-up research deepens, aprecitentan is expected to play a role in a wider range of cardiovascular diseases and bring new hope to patients for whom traditional treatments are ineffective.

Reference materials:https://go.drugbank.com/drugs/DB15059