Several treatments are approved for all types of PAH. However, how well they work and side effects of drugs used may not be the same in all of the different types of PAH. Other than calcium channel blockers, none of the drugs produce a significant lowering of the pulmonary arterial pressure and their long-term effects on survival are undefined. Ongoing studies support that the majority of patients are helped by these medication.
Calcium channel blockers
Patients who respond to short-acting dilator drugs at the time of heart catheterization should be treated with calcium channel blockers. Calcium channel blockers are generic medications that were initially approved to treat common high blood pressure. Patients may have dramatic reductions in pulmonary artery pressure associated with improved symptoms and improved survival now documented to exceed 20 years. However, only about 10% of patients respond to calcium channel blockers in the long term.
Endothelin Receptor Antagonists (ERAs)
Endothelin Receptor Antagonists (ERA) are oral medications that work by helping to prevent blood vessels from narrowing. Three approved ERA medications:
ERAs are approved treatments of PAH because they demonstrated improvement in exercise tolerance as measured by an increase in 6-min walking distance. One side effect may be swelling of the ankles.
Phosphodiesterase Inhibitors (PDE 5 Inhibitors)
Phosphodiesterase Inhibitors (PDE 5 Inhibitors) work by allowing the lungs to produce more of its own natural vasodilators (helps relax blood vessels) and help the heart improve its function. There are two approved PDE 5 Inhibitors medications:
Sildenafil and Tadalafil are approved for the treatment of PAH. Clinical trials have shown that both medications improve exercise tolerance in PAH. The most common side effect is headache.
A recently approved medication that works in a similar fashion, is known as a ‘Soluble Guanylate Cyclase Stimulators.” This medication may also be given to some patients with blood clots in the lung.
None of this class of drugs should be given to patients who are taking nitrate compounds.
Treatment of PAH with parenteral prostacyclins is the very first approved treatment for PAH and has proven to be the most effective. These medications work directly on the pulmonary blood vessels to counteract the disease and on the heart to allow it to recover. These medications are given either intravenously or subcutaneously (a.k.a. parenteral). There are three approved parenteral prostacyclin medications:
Epoprostenol (Flolan® and Veletri®)
Intravenous Treprostinil (Remodulin®)
Subcutaneous Treprostinil (Remodulin®)
Epoprostenol, the first FDA approved therapy is approved as a chronic intravenous treatment of PAH and it is the only drug to show improved survival. Clinical trials have demonstrated an improvement in symptoms and exercise tolerance. Chronic intravenous drug administration requires placement of a permanent central venous catheter and infusion through an ambulatory infusion pump system. Side effects include flushing, jaw pain and diarrhea, all of which are generally tolerated by most patients.
Treprostinil, an analogue (a very similar compound) of epoprostenol, is approved for PAH and may be given intravenously or subcutaneously. Local pain at the infusion site with the subcutaneous administration is very common and has caused most patients to switch to another therapy. Side effects are similar to those seen with epoprostenol.
The intravenous prostacyclins have the greatest beneficial effects as treatments for PAH, and are often effective in patients who have failed all other treatments. It may take several months to titrate the dose of epoprostenol or treprostinil upwards to optimal clinical efficacy, which can be determined by symptoms, exercise testing and heart catheterization. The major problem with intravenous therapy is infection related to the indwelling venous catheter, which requires close monitoring and diligence on behalf of the patient.
The prostacyclin drugs have also been developed to be administered by inhalation and as a pill.
Inhaled Treatment Options
Inhaled Treprostinil (Tyvaso™)
Oral treatment options
Oral Treprostinil (Orenitram®)
The inhaled and oral prostacyclin drugs were developed for patients who were unwilling or unable to take these medications by the parenteral route. Unfortunately, it is not possible to achieve the same blood levels of these drugs this way. Nonetheless, some patients will respond favorably, even though the dose achieved is quite low. The inhaled forms require inhalation treatments four or more times a day from a specially designed machine. Inhaled medications can produce coughing and other side effects. The oral forms cause considerable adverse stomach side effects and sometimes can only be tolerated in very small doses.
It is recommended that every patient diagnosed with PAH be treated. While no drug has been demonstrated to be superior as a first-line therapy, many prefer to initiate treatment with an oral or inhaled form of therapy. Patients who fail to adequately improve within the first two months of therapy should be switched to a different therapy, as there is concern that delaying a more effective treatment may allow the disease to progress and become less responsive to treatment. The use of these drugs in combination has become popular, but your physician will need to decide if adding a drug vs. switching a drug is preferable.
Lung transplantation is considered for patients who, while on an intravenous prostacyclin, continue to manifest worsening symptoms and right heart failure. Acceptable results have been achieved with heart-lung, bilateral lung, and single-lung transplant. The availability of donor organs often influences the choice of procedure. The benefit of lung transplantation is that it removes the underlying disease and patients can return back to a lifestyle typical of that prior to their illness. The major challenge is chronic rejection of the transplanted lung, which is associated with a survival of approximately 50% at five years.
Atrial septostomy (the creation of a hole in the heart to connect the two atrial or top chambers) was developed in 1983. While it does not specifically treat the PH, it does improve the function of the heart along with improved symptoms. In addition, it has a greater impact on improving survival than do many of the medications. Performing atrial septostomy requires training and experience. Few centers specialize in this procedure.