What is the difference between macitentan (Aoposu) and ambrisentan? Which one is more suitable for long-term treatment?

Macitentan (Macitentan) and ambrisentan (Ambrisentan) are both endothelin receptor antagonists (ERA) and are mainly used to treat pulmonary arterial hypertension (PAH). This class of drugs reduces pulmonary artery pressure, improves hemodynamics and delays disease progression by inhibiting the contraction and proliferation of endothelin-1 (ET-1) on vascular smooth muscle. However, although their mechanisms of action are similar, there are certain differences in molecular structure, receptor selectivity, pharmacokinetic properties and long-term clinical application, thus affecting their indications, tolerance and long-term treatment effects.

First, there are significant differences in pharmacological properties. Macitentan is a dual ET_A/ET_B receptor antagonist that can inhibit the activity of both receptors at the same time and has a high affinity for the ET_A receptor, but it still has a certain inhibitory effect on the ET_B receptor. In contrast, ambrisentan is a highly selective ET_A receptor antagonist and has almost no inhibitory effect on ET_B receptors. ET_BThe receptor is mainly involved in the clearance of endothelin and the release of nitric oxide (NO). Theoretically, the slight inhibition of ET_B by macitentan may lead to differences in vascular regulation, but clinical studies have shown that its comprehensive efficacy will not be weakened. The dual receptor inhibitory properties make macitentan more comprehensive in reducing pulmonary artery pressure and improving right heart function.

In terms of pharmacokinetics, macitentan has a long half-life, a more stable steady-state plasma concentration, and can be administered orally once a day, which is convenient for long-term management of PAH patients. Ambrisentan is also taken once daily, but its half-life is slightly shorter and it is more sensitive to fluctuations in blood concentration. In addition, macitentan has a lower risk of drug interactions and is less dependent on liver metabolism, while ambrisentan is mainly metabolized by the liver CYP3A4. Pay attention to potential interactions with CYP3A4 inhibitors or inducers. Therefore, for patients with multi-drug combination or slightly impaired liver function, macitentan has a slight advantage in drug tolerability and safety.

In terms of clinical efficacy, both drugs can improve 6 minute walking distance (6MWD), reduce pulmonary vascular resistance and improve functional class. However, large-scale long-term clinical trials have shown that macitentan has more significant advantages in delaying PAH disease progression and reducing clinical events. For example, the SERAPHIN study showed that macitentan can significantly reduce the risk of PAH-related hospitalization and death. However, long-term studies on ambrisentan mainly focus on improving exercise capacity and symptom relief, and there is a lack of long-term significant improvement data on mortality in large-scale randomized controlled studies.

In terms of safety and tolerability, both may cause angioedema, headache, nasopharyngeal congestion and abnormal liver function. However, ambrisentan's high selectivity for ET_A results in a slightly lower incidence of edema, while macitentan may slightly increase the risk of fluid retention in individual patients due to dual receptor inhibition. However, long-term studies of macitentan have shown that edema and liver function abnormalities can mostly be controlled through dose adjustment or supportive treatment, without affecting the feasibility of long-term treatment.

To sum up, there are certain differences between macitentan and ambrisentan in terms of mechanism, pharmacokinetics and long-term clinical efficacy. For PAH patients who require long-term management and focus on delaying disease progression and reducing the risk of clinical events, macitentan has more advantages in terms of pharmacological properties, steady-state plasma concentration, long-term survival benefit and comprehensive efficacy. Ambrisentan is suitable for patients with mild to moderate symptoms, good tolerance and high selectivity requirements for ET_A. The final drug selection should be based on the patient's specific condition, liver and kidney function, concomitant medications, and the physician's individualized assessment to achieve optimal long-term treatment effects.

Reference materials:https://www.drugs.com/