Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the arteries that carry blood from the heart to the lungs. PAH occurs when the openings in the blood vessels of the lungs get smaller and smaller. These smaller openings can be caused by the following:

• The walls of the arteries tightening
• The walls of the arteries becoming stiff and narrow from an overgrowth of cells The increased pressure in the pulmonary arteries strains the right side of the heart and it begins to fail, causing difficulty breathing and other symptoms. As PAH progresses, symptoms get worse.

There is no cure for PAH, but several medications like endothelin receptor antagonists (ERAs), prostacyclin analogues (PCAs) and riociguat, a soluable guanylate cyclase stimulator, are available to help slow the progression of changes in the pulmonary arteries and help reduce symptoms. Riociguat can be taken together with ERAs and PCAs.

In this study, the researchers want to learn about how well riociguat works, how safe it is when patients take it in 1 of these ways:

• alone
• with ERA
• with PCA
• with ERA and PCA The dosage for each patient will be decided by their doctor. The researchers will review information collected from the patients who have decided with their doctor to start riociguat treatment for their PAH. The study will include about 500 patients in the United States who are at least 18 years old. All of the patients will have either just started taking riociguat or will have been taking it for less than 3 months No investigational products will be administered in this study. Patients will be treated with the Standard of Care (SOC) for PAH. The SOC is the currently appropriate treatment in accordance with scientific evidence and agreed upon in collaboration between medical experts for PAH. There will be no study-mandated visits or treatments.

The patients will be in the study for up to 2 years. During this time, they will visit their doctor every 3 to 6 months as part of the Standard of Care. At these visits, the patients will answer questions about their PAH symptoms and whether they have any medical problems. They will also do exercise tests to see how well they are able to breathe and how tired they get while exercising. The doctors will perform other usual examinations which are part of the Standard of Care such as echocardiograms (images of the heart to show how the heart is working) and a right heart catheters (to measure the pressures in the heart) and will take the usual blood and urine samples.

Inclusion Criteria:

• Patients aged ≥18 years at the time of riociguat treatment initiation

• Diagnosis of PAH per National Institute for Health and Care Excellence (NICE) 2018 classification

• Decision to initiate treatment with riociguat as per investigator's routine treatment practice made prior to enrollment in the study

• Initiation of riociguat, as per the FDA-approved US label:

  • At enrollment OR
  • ≤90 days prior to enrollment, with a documented titration regimen (defined as all documented dose changes including, but not limited to: starting dose and dates and highest tolerated dose and dates)

• Signed informed consent

Exclusion Criteria:

• Previously treated with and discontinued use of riociguat for any reason prior to study enrollment (discontinuation defined as an interruption of therapy ≥30 days)

• Participating in any of the following:

  1. Blinded clinical trial
  2. Clinical trial involving an unapproved drug
  3. Investigational program with interventions outside of routine clinical practice

• Life expectancy <12 months

• Contraindicated to receive riociguat per the FDA approved US label

• Use of nitrates or NO donors in any form

• Use of PDE5 inhibitors

• PH associated with idiopathic interstitial pneumonias

• Unable or unwilling to provide informed consent

US patients aged ≥18 years, diagnosed with PAH, who are naïve to and initiating treatment with riociguat as per the FDA approved US label for PAH - either at study enrollment or have initiated riociguat within 90 days prior to study enrollment.

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.