Latest research progress on the combination of macitentan (Aopuxil) and tadalafil in the treatment of pulmonary arterial hypertension

Macitentan (macitentan) is a selective endothelin receptor antagonist (ERA) that works by blocking ET_A and ET_B Receptors, which inhibit endothelin-mediated vasoconstriction and vascular remodeling, have become one of the first-line treatments for pulmonary arterial hypertension (PAH). In recent years, researchers have combined macitentan with tadalafil (Tadalafil) for clinical use to explore the potential of dual drug combination therapy in improving hemodynamics, delaying disease progression, and improving patients' quality of life. The mechanism of dual drug combination is to act on two key vascular regulatory pathways at the same time: the endothelin pathway and the NO/cGMP pathway, thereby enhancing the efficacy on the basis of reducing pulmonary vascular resistance and reducing right heart load.

The latest multi-center randomized controlled trial shows that the combination of macitentan and tadalafil showed significant hemodynamic improvement in WHO functional class II–III grade PAH adult patients. The combination regimen significantly reduced pulmonary vascular resistance (PVR) during 16 weeks of treatment. Compared with single drug treatment, PVR could be reduced by up to 28%–29%. In addition, the combined treatment also significantly improved biomarkers such as 6 minute walking distance (6MWD ) and NT-proBNP , suggesting that patients' exercise tolerance and cardiac function have improved. These results indicate that dual drug combination is superior to single drug in short-term efficacy and can more effectively control disease progression.

Real-world studies also support the long-term clinical value of macitentan combined with tadalafil. Registration study data show that the one-year survival rate of patients receiving combination therapy can reach 88%–93%, and the hospitalization rate dropped significantly. Patients reported improved quality of life and enhanced ability to perform daily activities, demonstrating feasibility and clinical benefit for long-term use. It is worth noting that the combination of drugs can work at an early stage and help delay right ventricular remodeling and disease progression, thus having a positive impact on long-term prognosis.

In terms of safety, the adverse events of combined medication are generally controllable. Common side effects include hypotension, headache, facial flushing, and mild hematological abnormalities, but most are manageable. In clinical practice, blood pressure, liver and kidney function, and blood indicators need to be monitored regularly, and the dose should be adjusted or the medication interval extended when necessary to reduce potential risks. In addition, for patients with cardiovascular disease or abnormal renal function, individualized treatment plans should be developed under the guidance of a doctor.

In general, the combination therapy of macitentan (macitentan) and tadalafil (Tadalafil) has shown significant efficacy in the management of pulmonary arterial hypertension. This combination improves hemodynamic parameters and delays disease progression through a dual-target intervention mechanism, and has shown better long-term survival and quality-of-life improvement effects in the real world. With further research and accumulation of clinical experience, this combination regimen is expected to become an important strategy for initial or advanced treatment of PAH and provide patients with more efficient and safe treatment options.

Keyword tag:

Endothelin receptor antagonists, pulmonary arterial hypertension (PAH), targeted therapy, drug prices, medical insurance policies, imported drugs, domestic drugs, generic drugs, efficacy evaluation

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