Although the past decades of discovery and research have yielded drugs that improve prognosis and quality of life, the long-term survival rates for people living with PAH is still unacceptably low. A recent editorial offers thoughts on assessing risk for people living with this disease.

by Phyllis Hanlon, Contributing Writer  

In the past decades of discovery in pulmonary hypertension (PH), researchers have found drugs that improve prognosis and quality of life while reducing the burden of symptoms associated with WHO Group 1 PH (PAH, pulmonary arterial hypertension). However, the long-term survival rates of people with PAH is still unacceptably low. Teams of global researchers continue to look at what factors might predict patients at higher risk for mortality. They believe that, armed with this knowledge, clinicians can create more effective treatment plans to slow the progression of the disease.

Raymond L. Benza, M.D., who leads the PH program at Allegheny General Hospital, an accredited PH Care Center, and Mona Selej, MD, of the University of California San Francisco and Actelion Pharmaceuticals US, Inc., published an editorial that offered their thoughts on assessing risk in PAH.

Dr. Benza and his colleagues determined that since PAH is a complex disease, the best predictor of death is not any one variable, but a model that includes several different variables. The ideal risk assessment tool for patients should:

  • Be easy to use;
  • Predict accurately at any stage of PAH;
  • Apply to all patients with PAH regardless of sub-group;
  • Use the most recent available data;
  • Still be valid, even if some information is missing; and
  • Be flexible enough to change over time.

Additionally, the best tool for building such a model to identify risk factors should obtain data from a large group of people and be based on evidence, not just expert opinion. “Weighting,” which means that not all variables are treated the same and vary according to significance within the overall risk rating system, is another important factor, according to the authors.

The 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) recommended using 13 variables for risk assessment for patients with PAH. An overview of the 2015 European guidelines and some studies on which they were based was published in the European Respiratory Journal in April 2017. Marius M. Hoeper, M.D., Department of Respiratory Medicine, Hannover Medical School in Germany, led that review.

Data were analyzed from COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a large European study that looked at 1,588 newly diagnosed PAH patients in Europe who had not yet received treatment. COMPERA used a risk assessment tool that focused on only six items: World Health Organization (WHO) functional class (FC); six-minute walk distance (6MWD); N-Terminal pro—B-type Natriuretic Peptide or BNP (a blood test for cardiac failure); cardiac index (the heart’s performance in relation to the size of the patient); and mixed venous oxygen saturation (how much oxygen remains after the body’s tissues remove what they need).

The results of the COMPERA study showed one-year mortality rates after diagnosis at 2.8 percent in the low-risk group; 9.9 percent in the intermediate group; and 21.2 percent in the high-risk group. According to the authors, the strategy of using fewer variables proved to be accurate in all the PAH sub-groups and were still valid at follow up. Of note, patients who received PAH-targeted medical therapy and met low risk criteria for functional class, 6 min walk distance and NT-proBNP had a 5-year survival rate of 95 percent or more. A Swedish registry, as well as other studies and registries, have had a similar design with similar results. An interesting finding from the Swedish study reported that combination therapy proved to be better than monotherapy (taking just one drug). When that study took place in 2009, the authors noted that prescribing one drug was standard procedure; but recent evidence points to the effectiveness of using more than one drug.

Dr. Benza and his colleagues found the results from the European studies to be valuable. But they asserted that clinicians should not assume that patients fall cleanly into one of three distinct categories (low, intermediate or high-risk) and pointed out that certain risk factors, such as age, gender and PAH subtype, cannot be changed by treatment, but still should be included when projecting risk.

According to Dr. Benza, the perfect risk assessment tool has not yet been created. So he suggested researchers work as a community, rather than in silos. “Collaboration to devise a clinically meaningful prognostic algorithm, which can then be investigated in a collective, collegial and prospective manner, should be our goal.” In other words, increased cooperation among those who research PAH risk modeling could lead to more answers and better outcomes for patients.

Each PH patient is different. It is essential that you talk to your own doctor about what treatment options are best for you. For more information on finding a doctor or an accredited care center, visit