Pulmonary arterial hypertension (PAH) is a form of high blood pressure that affects the arteries that carry blood from the right side of the heart to the lungs. PAH is a progressive disease, meaning it worsens over time. However, treatment can help slow its progression and improve both life expectancy and quality of life.

Treatment varies based on PAH symptoms and their severity, PAH type, and other diseases or health conditions a person may have. Researchers have observed that factors like age, sex, race, and ethnicity can influence which PAH medications are prescribed and how well they work.

Keep reading to learn seven important facts about PAH treatment — information that can empower you or a loved one living with PAH to take a more active role in care.

1. Current Treatment Options Can Reduce Symptoms but Won’t Cure PAH

There’s no cure for PAH, but treatments can help slow disease progression and decrease your symptoms.

The U.S. Food and Drug Administration (FDA) has approved several medications to treat symptoms of PAH, a rare but serious disease that can quickly worsen if left untreated. Currently, there is no cure for PAH, but treatment of pulmonary arterial hypertension can help slow the disease and decrease your symptoms.

Many medications for PAH work as vasodilators, which means they help relax and open the blood vessels that run from the heart to the lungs. This helps increase blood flow and reduce stress placed on the heart — specifically, the right ventricle (its lower right chamber that pumps blood to the lungs).

The Four Main Pathways of PAH Medications

PAH medications work through four key biological pathways in the body. Each pathway involves a chemical in the body that helps control blood vessel function:

• Prostacyclin
• Endothelin
• Nitric oxide
• Activin

Treatment differs based on individual circumstances, so each person needs to work closely with their healthcare team to find out which medication suits them best.

2. Some PAH Treatments Target the Prostacyclin Pathway

All blood vessels in the body have an inner layer made of cells called vascular endothelial cells. These produce a chemical called prostacyclin, which attaches to special receptors on the smooth muscle that surrounds blood vessels.

Prostacyclin connects to this receptor much like how a key fits into the lock of a door. Once this connection is made, multiple chemicals interact, leading the smooth muscle to relax. This relaxation of smooth muscle enlarges the opening of blood vessels, increasing blood flow to the entire body.

In people with PAH, prostacyclin levels are often too low. Medications that mimic prostacyclin help fill that gap, improving blood flow and lowering the high pressure in the lungs.

These drugs can cause systemic vasodilation (enlargement of blood vessels in the body). Healthcare professionals consider this group of medications to work well for the high blood pressure that accompanies PAH, but these drugs can have side effects. Drugs that work on this pathway are often doctors’ first choice for treating the most severe forms of PAH.

All of these medications need careful dose monitoring by a doctor. Depending on the drug, it may be administered through a vein, inhaled, or swallowed as a tablet.

3. Some PAH Treatments Work on the Nitric Oxide Pathway

The inner layer of vascular cells in all blood vessels makes nitric oxide. This gas plays a key role in controlling blood pressure by helping blood vessels relax. When the inner layer of a blood vessel makes nitric oxide, the molecule travels to the smooth muscle and relaxes it. This allows blood vessels to open up and increases blood flow.

People with PAH have low levels of nitric oxide in their lungs. This deficiency adds to the tightening of the arteries leading to the lungs, creating the high blood pressure and increased risk of blood clots seen in PAH.

In addition, an enzyme called phosphodiesterase-5 (PDE5) lives in the walls of all blood vessels. The job of PDE5 is to block the effect of nitric oxide.

When PDE5 blocks the effect of nitric oxide in people with PAH — who already have too little nitric oxide in the blood vessels of their lungs — it becomes even harder for the body to relax the blood vessels that run from the heart to the lungs.

Medications that work on this pathway to block PDE5 are known as PDE5 inhibitors. A PDE5 inhibitor allows the body’s nitric oxide to work more effectively to relax the blood vessels. Researchers have noted that doctors’ prescribing patterns for PDE5 inhibitors differ based on factors such as type of PAH, ethnicity, and race.

Nitric oxide also turns on another enzyme called soluble guanylate cyclase (sGC). This enzyme helps increase blood flow in the entire body by causing vasodilation of all blood vessels. Medications that serve as sGC stimulators help the body make more nitric oxide, thus decreasing PAH symptoms.

4. Another Group of PAH Drugs Affects the Endothelin Pathway

Endothelin is a molecule made in the inner layer of all vascular cells in the body. From there, endothelin travels to the deeper smooth muscle cells, leading to the narrowing of the blood vessels. People with PAH usually have too much endothelin, causing the blood vessels of their lungs to narrow and restricting blood flow to the lungs.

Medications called endothelin receptor antagonists (ERAs) counteract this effect, which helps promote relaxation of the blood vessels. This, in turn, can help to improve symptoms and even increase survival.

Research suggests that ERA effectiveness may vary somewhat depending on a person’s sex and race, which is why a personalized treatment approach is so important.

5. The Final Group of PAH Drugs Affects the Activin Signaling Pathway

The fourth major pathway involved in PAH is called the activin signaling pathway. It’s part of a larger family of cell signals known as the transforming growth factor-beta (TGF-beta) superfamily.

In PAH, too much activin is often produced. This chemical increases abnormal growth and expansion of the blood vessel walls. Over time, this can cause the pulmonary arteries to become stiff, inflamed, and narrowed, making it harder for blood to flow and the heart to do its job.

Medications that block the activin pathway may help by relaxing and repairing damaged blood vessels in the lungs. This can reduce pressure, make breathing easier, and improve energy levels and quality of life for people living with PAH.

6. PAH Severity Helps Guide Treatment Choices

There are four classes of PAH. Doctors select medications based on your class and severity of PAH.

Doctors choose different PAH medications based on how advanced the disease is and how it affects a person’s daily activities. The World Health Organization (WHO) has established four functional classes of PAH to describe severity:

• Class 1 — No limits on physical activity
• Class 2 — Slight restriction to physical activity
• Class 3 — Moderate limits on physical activity
• Class 4 — Symptoms even at rest and severely limited physical activity

Determining the Best Treatment

Doctors often start with a test called acute pulmonary vasodilator testing. This test allows a doctor to check if the lung arteries quickly relax in response to specific vasodilating medications. If lung arteries relax and open up in response to this test, the doctor may prescribe a calcium channel blocker depending on the person’s condition and symptoms.

If a calcium channel blocker is not effective or vasodilator testing does not work, a doctor may prescribe one or a combination of medications that affect one of the four pathways discussed above.

People with class 3 or 4 PAH who do not improve with vasodilator testing may begin a combination of prostacyclin, endothelin, and PDE5 therapy.

In addition, doctors may recommend supportive therapies and medications like:

• Diuretics (water pills) to help treat swelling
• Anticoagulants, which help prevent blood clots
• Lifestyle changes, including heart-healthy eating, regular movement, and pulmonary rehab

Working closely with your healthcare team to monitor symptoms and adjust treatment over time is key to living with PAH.

7. Most People With PAH Take a Combination of Medications

Using more than one type of medication, known as combination therapy, can improve the quality of life for people with pulmonary arterial hypertension.

Taking more than one type of PAH medication can improve the quality of life for people with PAH.

One clinical trial examined using two PAH medications together in 500 people with class 2 or 3 PAH who had not previously taken medication for the condition. Researchers found that the combination — one ERA and one PDE5 inhibitor — was more effective for treating PAH than using either alone. Some side effects were more common with combination therapy, including swelling, headache, and nasal congestion.

Another study on 18 people with class 3 or 4 PAH showed that taking an endothelin receptor antagonist, a prostacyclin analog, and a PDE5 inhibitor together helped decrease the risk of heart failure.

In 2024, a single-tablet combination of an endothelin receptor antagonist and a PDE5 inhibitor was approved by the FDA to treat people with class 2 or 3 PAH.

Be sure to talk to your doctor when starting, switching, or combining medications for PAH. Based on the severity and symptoms of your PAH, they can help determine the best treatment plan for you.

Talk With Others Who Understand

On myPHteam, the social network for people with pulmonary hypertension and their loved ones, more than 56,000 members come together to ask questions, give advice, and share their stories.

Are you living with pulmonary arterial hypertension? Which treatments have helped your symptoms? Share your experience in the comments below, start a conversation by posting on your Activities page, or connect with like-minded members in Groups.