What medications are used to treat early-stage PAH?

Arterial blood pressure is the force that blood exerts on the walls of the arteries as it travels through the body. Multiple factors influence blood pressure, including the efficiency with which the heart pumps blood (cardiac output), the elasticity of the blood vessels, and peripheral vascular resistance, which is how much the body’s smaller blood vessels push back against circulating blood.

Pulmonary arterial hypertension (PAH) is a disorder that causes structural changes in the blood vessels inside the lungs. These structural changes increase the thickness of the blood vessel walls, which causes blood pressure to increase. While the underlying causes can be inherited genetic mutations or other health conditions, in many cases the cause of PAH is unknown.

While PAH can occur at any age, it most often affects females between the ages of 30 and 60, and people who are over the age of 65.

Treating early-stage PAH

Early symptoms of PAH are typically mild and nonspecific, meaning symptoms overlap with many other (and more common) conditions. Early symptoms may include shortness of breath (especially during activity), fatigue, chest pain, dizziness, fainting, and swelling. As the disease progresses, it can lead to right-sided heart failure and other serious and potentially life-threatening complications.

Early diagnosis and treatment are associated with better outcomes. While there is no cure for PAH, there are therapies that can help manage symptoms, reduce the risk of complications, slow disease progression, and help a person maintain a better quality of life.

Medications are the main treatment. Some people begin treatment with a single medication, but many people with PAH will take two or more medications as part of their treatment plan. A treatment plan will often include oral medications, but it may also include medications that are given as infusions, injections, or inhaled.

PAH medications can be categorized based on how they work inside the body:

Nitric oxide pathway medications

One of the ways the body balances blood pressure is through vasodilation and vasoconstriction. Vasodilation is the relaxing of blood vessels to allow blood to move through more easily and reduce blood pressure. Vasoconstriction is the reverse, the narrowing of blood vessels to increase blood pressure.

Nitric oxide (NO) is a vasodilating substance produced in the body. PAH reduces the body’s ability to produce and use NO.

Some drugs that treat PAH help the body maintain higher amounts of NO or increase the body’s sensitivity to NO to help reduce blood pressure:

• PDE5 Inhibitors. Phosphodiesterase-5 (PDE5) inhibitors help the body maintain higher levels of a substance called cyclic guanosine monophosphate (cGMP), which helps blood vessels stay relaxed. These drugs are a common initial treatment for PAH.
• sGC Stimulators. Soluble guanylate cyclase (sGC) stimulators increase the body’s sensitivity to nitric oxide.

Endothelin receptor antagonists (ERAs)

ERAs block endothelin-1 (ET-1), a substance that is often produced in abnormally high amounts in the lungs of people with PAH. Abnormally high amounts of ET-1 contribute to vasoconstriction and the overgrowth of cells that make up blood vessel walls (which causes blood vessel walls to become thicker and less flexible).

Because of the risk of serious side effects, these drugs are only available through a restricted distribution program. Liver function monitoring and monthly pregnancy tests (due to risk of severe birth defects) are required when taking these medications.

Prostacyclin analogues

Prostacyclin is a chemical that naturally occurs in the body that acts as a vasodilator, Prostacyclin analogues are medications that mimic prostacyclin.

There are multiple prostacyclin analogues available in multiple formulations, including options that are taken as infusions, inhalers, and oral medications. While advanced PAH often requires continuous intravenous (IV) infusions of prostacyclin, oral or inhaled prostacyclin analogues may be used in earlier stages.

Other medications and therapies

In addition to the medications above, a treatment plan may include other types of therapies:

• Other types of vasodilating medications
• Diuretics to reduce fluid buildup
• Oxygen therapy
• Medications to prevent blood clots
• Lung and heart-lung transplantations (may be recommended in severe cases where medications no longer work)
• Lifestyle interventions, including light physical activity

Multiple new treatments for PAH are under development, and clinical trials may be a topic to discuss with a healthcare team. A disease-modifying therapy that blocks signals that cause blood vessel walls to overgrow and thicken became available in 2024.

Work with your healthcare team

There is no one-size-fits all approach to treating PAH, and your best source of information about medications will be a healthcare provider. When discussing any medication, it’s important to consider potential benefits, potential risks, and anything that may prevent you from taking a medication, such as cost or complex dosing schedules.