Pulmonary arterial hypertension (PAH) has an estimated prevalence of 15 to 50 cases per million persons, but occurs with greater frequency in certain patient populations, including persons with HIV, systemic sclerosis, and/or sickle cell disease. PAH is diagnosed when the mean pulmonary arterial pressure (mPAP) is 25 mm Hg or higher at rest (normal mPAP, ≤20 mm Hg). Many physicians consider an mPAP of 21 mm Hg to 24 mm Hg as borderline elevated and of uncertain clinical significance. Once diagnosed, treatment focuses on reducing symptoms, slowing disease progression, and improving quality of life. This is often achieved through lifestyle changes, pharmacologic interventions, and surgery in select cases. What follows is a brief overview of some of the medications that are currently used to treat PAH.
Endothelin Receptor Antagonists
Patients with PAH often have high levels of endothelin, a group of vasoconstrictive peptides. Endothelin receptor antagonists (ERAs) block endothelin receptors, improving blood flow. Selective and nonselective ERAs are available for treating PAH, including bosentan (Tracleer) and ambrisentan (Letairis). Both agents have been shown to improve distance on the 6-minute walk test and time to clinical worsening. Liver monitoring is required when using either agent, as elevated transaminase levels have been observed. None of these agents have shown mortality benefits.
Phosphodiesterase-5 (PDE-5) inhibitors relax the muscles and facilitate blood flow through the blood vessels in the lungs. These agents were originally used to treat erectile dysfunction, but have shown benefits in treating PAH. Sildenafil (Viagra, Revatio), tadalafil (Cialis, Adcirca), and vardenafil (Levitra) have shown improvement in distance on the 6-minute walk test; however, only sildenafil and tadalafil have been approved by the US Food and Drug Administration as a treatment for PAH. These agents are generally well tolerated. The most commonly reported adverse events include gastrointestinal upset, dizziness, and vision problems.
Patients with PAH have low prostacyclin synthase levels, reducing the production of prostacyclin and preventing adequate vasodilation. Prostanoids open narrowed blood vessels, improving blood flow. Epoprostenol (Flolan) is the first drug specifically approved for the treatment of PAH and has shown efficacy in treating PAH related to congenital heart disease, lupus, scleroderma, and associated with the use of diet pills and stimulants. A major drawback of this treatment is that its effects last only a few minutes, necessitating use of an intravenous (IV) catheter and small pump to enable continuous infusion. Patient compliance is a concern, as patients must mix their own medication on a daily basis. Reported adverse effects include jaw discomfort, headache, gastrointestinal problems (eg, nausea, diarrhea), leg cramps, and pain and infection at the IV site. Increased exercise capacity and survival have been reported with this medication for patients with advanced disease.
Other available prostanoids include treprostinil (Remodulin), which is the most similar to epoprostenol but can be administered subcutaneously due to its longer half-life, and iloprost (Ventavis), which is inhaled every 3 hours through a nebulizer. Adverse events associated with iloprost include chest pain, headache, nausea, and breathlessness. None of these prostanoids have shown a mortality benefit.
Chronic Adjuvant Therapies
Patients with PAH often require use of adjuvant therapies to avoid complications and reduce symptoms associated with their disease. Common adjuvant therapies include anticoagulants such as warfarin (Coumadin, Jantoven) to prevent blood clots in the lungs; calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem, Tiazac), and nifedipine (Adalat, Procardia), to reduce constriction in the pulmonary arteries; diuretics to reduce systemic congestion; digoxin (Lanoxin) to improve heart rate and alleviate symptoms of congestive heart failure; and inhaled oxygen to reduce dyspnea.