New drugs help expand treatment options for pulmonary hypertension.
The common, garden-variety type of high blood pressure (what doctors call hypertension) affects vessels throughout the body. But a less common form affects the arteries that carry blood from the right side of the heart to the lungs. The vessels tighten, become stiff and thick, or develop blood clots.
Known as pulmonary hypertension, the condition affects both the lungs and the heart. The right side of the heart works harder to pump blood to the lungs. At the same time, damage to the small vessels within the lungs means less oxygen reaches the blood. Over time, the heart’s right ventricle changes shape and can’t function effectively, says Dr. Bradley Maron, a cardiovascular disease specialist at Harvard-affiliated Brigham and Women’s hospital. “When this happens, people don’t do well. They get sick, go to the hospital often, and tend to have a shorter life span.”
Pulmonary arterial hypertension
In pulmonary arterial hypertension (PAH), the arteries to the lungs become stiff and inflexible. As a result,
Illustration: Scott Leighton
The root of the problem
Pulmonary hypertension can be tricky to diagnose because the symptoms—shortness of breath, fatigue, dizziness, swelling, and heart palpitations—aren’t specific. They are often attributed to more common problems such as asthma, lung diseases from smoking, or even anxiety. The only sure way to identify pulmonary hypertension is to insert a catheter into the right side of the heart and directly measure the blood pressure in the pulmonary arteries.
What’s more, pulmonary hypertension can arise from a wide variety of health problems. Most of the time, the problem stems from underlying heart or lung disease. In some instances, the elevated pulmonary blood pressure is due to a blood clot that grows on the artery wall. Surgery on the lung arteries provides a definitive cure in these cases.
In 2013, the FDA approved two novel drugs for PAH and an easier delivery method for a third. One of the new entries, macitentan (Opsumit), a member of the class known as endothelin-receptor antagonists, is important because clinical trials showed that it could delay the progression of the disease. The second new drug, riociguat (Adempas) targets a novel signaling pathway to relax the blood vessel walls. Although its effect on the arteries is similar to that of the PDE5 inhibitors, it may be effective in people who do not respond well to the older class of drugs. The third offering is an oral version of a prostacyclin drug called treprostinil (Remodulin). Previously, this medication had to be given directly into a vein using an implanted pump.
A rare form of the condition, known as pulmonary artery hypertension (PAH), can be especially severe, says Dr. Maron. “It generally affects younger people, often women who have connective tissue disease such as scleroderma or lupus. In most cases, the cause is unknown. But it may be associated with genetic and molecular factors that destroy the normal structure of the pulmonary blood vessels.”
Treatments for most forms of pulmonary hypertension target heart function or remove the arterial blockage causing the problem. But for people with PAH, there have been no easy answers. In recent years, however, the outlook has brightened, thanks to new medication strategies that directly target the poorly functioning blood vessels.
Expanding the arteries
The first drugs to treat PAH were prostacyclins, which help blood vessels relax. Since then, other medications have joined the list, including those that help prevent blood vessels from constricting (called endothelin-receptor antagonists). Others include PDE5 inhibitors such as sildenafil (Viagra), which open the arteries and are better known for treating erectile dysfunction.
There is still a long way to go in PAH treatment, concedes Dr. Maron. The treatments are expensive, don’t work well for all people, and may have serious side effects. “But with the greater ability of individualized treatment, we can start therapy earlier rather than later in people who can tolerate these medicines,” he says.