Researchers are having a look at the evidence for using a multidrug approach in treating pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs.
The researcher said the multidrug approach has a trajectory of progress, which is exemplary among cardiopulmonary diseases.
Currently, there are 14 FDA-approved therapies for the treatment of PAH, all of which target the release of nitric oxide using phosphodiesterase type-5 (PDE5) inhibitors like sildenafil. Also, the current treatments target the endothelin receptor axis and the prostacyclin pathways.
These 14 therapies and other treatments are undergoing investigation in clinical trials since 2004.
One researcher explained that the rationale for using a multidrug approach in PAH stems from the multidrug approach used in other cardiovascular disorders, stating, “A strong precedent exists in support of diversifying drug therapy to manage a wide spectrum of diseases, including highly prevalent cardiopulmonary disorders such as systemic hypertension, atrial fibrillation, myocardial infarction and others.”
Patients with PAH were first given epoprostenol (prostacyclin), the only available PAH therapy from 1995 until 2001. Some patients received bosentan (endothelin receptor antagonist).
The researchers found that there was a significant improvement in patients who received epoprostenol and bosentan than those who received epoprostenol and a placebo.
“The wider availability and favorable safety profile of PDE-Vi drugs made add-on treatment with this class as an important consideration, and one that could be tested in a larger patient population than preceding studies,” the researcher wrote.
The evidence for multidrug therapy also includes a combination of therapy in patients using ambrisentan (endothelin receptor antagonist) and tadalafil (PDE5 inhibitor).
Researchers have also looked at the landmark multicenter Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) study that enrolled 500 PAH patients, which showed a greater reduction in biochemical evidence of heart failure.
The author wrote, “Up-front triple therapy is on the horizon, as more data using this approach becomes available.”
“Cutting-edge clinical trial enrollment methods that integrate pathobiological measures will continue to drive the field toward precision medicine, while mounting clarity on the cardiopulmonary hemodynamic spectrum of risk is likely to widen the range of patients for whom clinical trial enrollment is a consideration,” the author added. The article was originally published in the American Journal of Managed Care (AJMC), a leading peer-reviewed journal dedicated to issues in managed care.
