Differences and combination therapy between macitentan (Aoposu) and bosentan in the treatment of pulmonary arterial hypertension

Macitentan (Macitentan) and bosentan (Bosentan) are both endothelin receptor antagonists (ERA), is an important drug in the treatment of pulmonary arterial hypertension (PAH), but there are certain differences in pharmacological properties, clinical application and safety. At the same time, it can be considered in combination with other drugs for comprehensive treatment under certain circumstances.

Macitentan is an oral dual endothelin receptor antagonist that can selectively inhibit ET-A and ET-B receptors, inhibit vasoconstriction and vascular remodeling, thereby reducing pulmonary artery pressure and improving right heart function. Compared with bosentan, macitentan has a longer half-life and more stable blood concentration, so it can maintain effective blood levels once a day and has better compliance. Clinical studies have shown that macitentan can significantly improve 6 minute walking distance (6MWD), cardiac function class and hemodynamic indicators, and reduce the risk of PAH related hospitalization and death.

Bosentan is also an oral endothelin receptor antagonist, but its early development was a non-selective dual receptor inhibitor. ET-A and ET-B have relatively balanced inhibitory effects and are usually administered twice daily. Bosentan is equally effective in improving exercise tolerance and pulmonary hemodynamics, but liver enzyme levels need to be monitored closely in patients with poor hepatic function because of its higher potential for hepatotoxicity than macitentan. In addition, the blood concentration of bosentan is greatly affected by food, so meal times and dosage adjustments need to be taken into consideration when administering.

In terms of combination therapy, macitentan or bosentan can often be used in combination with phosphodiesterase-5 inhibitors (PDE5i) such as sildenafil or tadalafil to achieve the dual effects of vasodilation and pulmonary vascular remodeling. Combined therapy can significantly improve patients' exercise capacity, quality of life and hemodynamic indicators, and delay disease progression. Clinical guidelines suggest that for medium- and high-risk patients whose monotherapy fails to achieve the desired effect or whose symptoms are still obvious, a combination treatment regimen of ERA and PDE5i can be used, with dose adjustment and monitoring based on patient tolerance.

In addition, macitentan shows better tolerability in terms of long-term safety, and the incidence of abnormal liver function and edema is lower than that of bosentan, making it more advantageous in long-term maintenance treatment. Bosentan is still a PAH in many countriesPAHIt is a first-line treatment drug, but adverse reactions such as liver function, hemoglobin, and swelling must be strictly monitored during use. Combination therapy needs to follow the principle of individualization, combined with patient risk stratification, hemodynamic indicators and daily functional status, and regular review of 6MWD, NT-proBNP and cardiac ultrasound to optimize treatment effect and safety.

In general, macitentan and bosentan are both endothelin receptor antagonists in the treatment of PAH, but macitentan has better compliance and higher tolerability, while bosentan has a longer history of early use and rich clinical experience. The two can be used in combination with PDE5 inhibitors and other drugs in individualized treatment plans to achieve the dual effects of vasodilation and cardiac function protection. Clinical application should select appropriate drugs based on the patient's specific conditions, and regularly evaluate efficacy and safety to delay the progression of pulmonary hypertension and improve patients' quality of life.

Keyword tags: macitentan, bosentan, pulmonary hypertension, endothelin receptor antagonist, combination therapy

Reference materials:https://en.wikipedia.org/wiki/Macitentan