What is the relationship between Macitentan (Endothelin receptor antagonist) and fluid retention?

From the Guidelines

Macitentan is not significantly associated with fluid retention as a side effect, according to the most recent and highest quality study. This medication, which belongs to the endothelin receptor antagonist class, is primarily used to treat pulmonary arterial hypertension (PAH). The study 1 found that the incidence of fluid retention was no different from the placebo group, suggesting that edema may not be a significant side effect for this medication.

Key Points to Consider

• The endothelin receptor antagonist class of medications, including macitentan, can potentially affect sodium and water balance in the body, but the actual incidence of fluid retention with macitentan is not significantly higher than with placebo 1.
• Patients taking macitentan should still monitor for signs of fluid retention, including sudden weight gain, increased swelling in extremities, shortness of breath, or decreased urine output, as a precautionary measure.
• Regular weight monitoring is recommended for all patients with PAH, regardless of the treatment they are receiving.
• If fluid retention becomes problematic, healthcare providers may adjust the dose, add a diuretic like furosemide, or recommend sodium restriction, although this is not commonly required for patients taking macitentan 1.
• Patients with pre-existing heart failure or kidney disease should be monitored more closely, as they have a higher risk for fluid retention and other complications.

Important Considerations for Clinical Practice

• The benefits of macitentan in treating PAH often outweigh the potential risks, including the low risk of fluid retention 1.
• Healthcare providers should carefully consider the individual patient's risk factors and medical history when prescribing macitentan or any other medication for PAH.
• The study 1 demonstrated the efficacy and safety of macitentan in patients with PAH, with a significant reduction in clinical worsening events and improvement in 6-minute walk distance.

From the Research

Relationship between Macitentan and Fluid Retention

• Macitentan-treated patients were quantitatively more likely to experience significant fluid retention versus placebo, as observed in the MELODY-1 study 2.
• The difference in fluid retention was apparent within the first month of treatment, with 7 macitentan-treated patients and 4 placebo-treated patients experiencing significant fluid retention or worsening functional class 2.
• In contrast, other studies suggest that macitentan has a favorable safety profile with respect to hepatic safety and edema/fluid retention, compared to other endothelin receptor antagonists such as bosentan and ambrisentan 3, 4.
• However, a more recent study (SERENADE) found that macitentan neither lowered NT-proBNP nor improved heart failure outcomes, and more macitentan-treated patients developed fluid retention (16 [23%] versus 10 [14%]) and cardiac adverse events (33 [46%] versus 22 [31%]) versus placebo 5.
• The safety and tolerability of macitentan in the management of pulmonary arterial hypertension have been updated, with real-world use revealing a reduced risk of hospitalizations related to pulmonary arterial hypertension and improved health-related quality of life scores, although the risk of fluid retention remains a concern 6.