PAH Prognosis and Risk

Advances in PAH
Why is it critical to reach low risk in 1 year?
Extensive patient registry data informs prognosis

Advances in PAH

Advances in understanding pulmonary arterial hypertension (PAH) continue, constantly reshaping how we approach care and treatment of this challenging disease. PAH care decisions are now driven by combining the results of functional capacity, biomarkers, and hemodynamic parameters to forecast potential complications and estimate survival as part of a more comprehensive prognosis. This information provides the foundation for care and treatment plans today.¹

The overall approach of PAH has shifted from a reactive "take action with decline" to a proactive, goal-based approach highly influenced by a patient's calculated risk score and their right heart health. For most patients, the generally accepted treatment goals are achieving and maintaining low-risk status, ideally within the first year.¹

Graph showing the impact on survival per change in risk category from baseline to follow-up (3 months to 2 years) in the COMPERA Registry

Improve prognosis by achieving low-risk

The effort to understand patient prognosis is based on data collections from large, retrospective global registries that follow thousands of patients with PAH over long periods. These data help make informative predictions of patient survival according to their risk scores.^2,3

Global registries consistently reveal that patients who achieve low-risk status, particularly in their first year after diagnosis, have a better likelihood of survival. Setting a treatment goal to achieve low-risk status in the first year of therapy can help give your patients a better long-term prognosis.^3-6

For patients not at low risk, guidelines and consensus recommendations indicate treatment plan adjustments, including the addition of therapies from different treatment classes.¹

“We have very well-established data now that tells us our goal should be to get a patient to low-risk status. We know that their prognosis is going to be much better if we get them there.”

— Vallerie McLaughlin, MD, Director, Pulmonary Hypertension Program and endowed Professor of Medicine, University of Michigan, Ann Arbor, MI

For example, as shown by data from the SPAHR Registry, patients who stayed at or improved to low risk at first follow-up had a significantly better 5-year survival rate than those who were intermediate or high risk.* These data validate the critical need for comprehensive risk assessments and the urgency to treat to achieve low-risk status in patients with PAH.⁴

*The median time from diagnosis to first follow-up was 4 (IQR 3-5) months, but within a year of diagnosis.⁴

5-year Kaplan-Meier survival estimates based on risk category (P<0.001)^4†

Image Description

5-year Kaplan-Meier survival estimates based on risk category (P<0.001)⁴

96% of patients who improved to "low risk" were estimated to survive to 5 years
89% of patients who were stable "low risk" were estimated to survive to 5 years
50% of patients who were stable "intermediate risk" or "high risk" were estimated to survive to 5 years
43% of patients who worsened to "intermediate risk" or "high risk" were estimated to survive to 5 years

^†A Swedish observational study (2008-2016) of 530 patients with PAH using the SPAHR Registry: Patients were assessed with 8 risk assessment variables from the 2015 ESC/ERS Treatment Guidelines (WHO FC, 6MWD, RA area, NT-proBNP, mRAP, pericardial effusion, CI, and SvO₂).⁴

Guidelines recommend low-risk goal

Low-risk status is the PAH treatment goal established by 2022 ESC/ERS Treatment Guidelines and supported by the 2024 WSPH Proceedings.^1,7 These recommendations are based on the compelling real-world data collected from more than 6000 patients during ~20 years in registries across the globe. By improving patients’ risk status, the data show that survival may be extended.^1,3-6

Detailed registry information provided the data to generate risk assessment methods. Calculating a patient’s risk score consistently can help you determine your patient’s estimated survival and track their progress to low risk.^1,7

Aim for low risk: Find the risk calculation method that will work for you and your practice

Examine Risk Calculators

Why is it critical to reach low risk in 1 year?

According to treatment guidelines, patients who are not at low risk at follow-up are considered to have an inadequate treatment response, and therapy escalation is recommended. While the baseline risk assessment informs the initial management plan, reassessment within 3 months is required to determine whether achieving low risk in the first year is likely. For patients not at low risk, making timely treatment adjustments is critical to their outcomes.¹

Aim for low risk, even in intermediate-risk patients

Getting to low-risk status is critical for patient outcomes. In a study using the SPAHR Registry,* patients who did not reach low-risk status at first follow-up^† were unlikely to achieve low-risk status in the following 2 years. Indeed, among patients who were at intermediate risk at year 1, only 12% made it to low risk by year 3, while 43% had either died or had a lung transplant by year 3.⁸

*A Swedish observational study (2008-2019) of 530 patients with PAH. Patients were initiated on treatment within 3 months of diagnosis. Image is part of main cohort of 340 patients aged ≤75 years with <3 comorbidities who were at intermediate-risk status at year 1; patients were on mono (35%), dual (48%), or triple PAH therapy (12%), or standalone CCB (1%).⁸^†First year of follow-up was defined as the visit registered closest to 12 months in a window of 6 to 18 months after baseline, which is the day of diagnosis.⁸

Image Description

For patients at intermediate risk at year 1⁸:

12% improved to low risk at year 3
38% remained at intermediate risk at year 3
7% worsened to high risk at year 3
43% were deceased or had undergone a transplant at year 3

Stable is not the same as low risk

In studies from the COMPERA Registry, patients who remained at intermediate-risk status from baseline assessment to follow-up (3 months to 2 years) had only a ~50% chance of survival over 5 years.³

Impact on survival per change in risk category from baseline to follow-up (3 months to 2 years) in the COMPERA Registry³

Adapted from Hoeper MM, et al. Eur Respir J. 2017;50(2):1700740.

Image Description

Impact on survival per change in risk category from baseline to follow-up (3 months to 2 years) in the COMPERA Registry³:

Stable low-risk patients had the highest survival at 5 years
Patients who worsened from low to intermediate risk had the next highest survival at 5 years
Stable intermediate-risk patients had lower survival than patients who improved from intermediate risk to low risk
Patients who worsened from intermediate to high risk had a lower survival than patients who improved from high to intermediate risk at 5 years
Stable high-risk patients had the lowest survival at 5 years

It is important to remember that 2022 ESC/ERS Treatment Guidelines recommend that the treatment goal is to strive for low-risk status, not the perception of "stability."^1,9 Even when patients appear “stable,” the risk for disease progression exists.^1,3 Calculating risk using a multiparameter method provides an objective measure of disease status.¹

Extensive patient registry data informs prognosis

ESC/ERS Treatment Guidelines rely on both clinical trial data as well as data from registries to generate their recommendations.¹ Multiple ongoing, retrospective registries from the US and Europe, including from Sweden and France, have collected countless data from more than 6000 patients with PAH. Each of these registries contains its own inherent nuances, as they reflect the varied populations and care systems from their specific countries.^3-6

Consistent data span multiple registries

These rich datasets repeatedly demonstrate that patient survival rates improve when they achieve low-risk status. Across registries, patients who achieved or maintained low-risk status at first follow-up within 1 year after diagnosis had improved survival at 1 and 5 years.^3-6,10* This improved prognosis is seen in spite of the intrinsic differences within the registries and serves to emphasize the strength of the data.

Survival of low-risk patients across registries^3-6,10*

*Survival were based on low-risk status at baseline and follow-up for SPAHR and COMPERA and low-risk status at follow-up for the French Registry and REVEAL.^3-6^†Low risk defined as patient having 4 low-risk criteria: WHO/NYHA FC I/II, 6MWD >440 m, RAP <8 mm Hg, and CI ≥2.5 L/min/m².⁵^‡Low risk defined as patient having 3 low-risk criteria: WHO/NYHA FC I/II, 6MWD >440 m, BNP <50 ng/L or NT-proBNP <300 ng/mL.⁵

Image Description

Survival of low-risk patients across registries.⁵*

1-year survival with low-risk status

SPAHR⁴: 100%
COMPERA³: 97%
French⁵: 100%^†
French⁵ (noninvasive): 100%^‡
REVEAL 2.0^6,10: 98%

5-year survival with low-risk status

SPAHR⁴: 89%
COMPERA³: 76%
French⁵: 91%^†
French⁵ (noninvasive): 97%^‡
REVEAL 2.0^6,10: 89%

*Survival were based on low-risk status at baseline and follow-up for SPAHR and COMPERA and low-risk status at follow-up for the French Registry and REVEAL.^3-6^†Low risk defined as patient having 4 low-risk criteria: WHO/NYHA FC I/II, 6MWD >440 m, RAP <8 mm Hg, and CI ≥2.5 L/min/m².⁵ ^‡Low risk defined as patient having 3 low-risk criteria: WHO/NYHA FC I/II, 6MWD >440 m, BNP <50 ng/L or NT-proBNP <300 ng/mL.⁵

REVEAL and European registries support risk assessment calculations

Investigate Registries

Hone your treatment of PAH with risk assessment

Learn About Risk Assessment

6MWD=6-minute walk distance; BNP=B-type natriuretic peptide; CCB=calcium channel blocker; CI=cardiac index; COMPERA=Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; ERS=European Respiratory Society; ESC=European Society of Cardiology; FC=functional class; IQR=interquartile range; mRAP=mean right atrial pressure; NT-proBNP=N-terminal pro–B-type natriuretic peptide; NYHA=New York Heart Association; RA=right atrium/right atrial; RAP=right atrial pressure; REVEAL=Registry to EValuate Early And Long-term pulmonary arterial hypertension disease management; SPAHR=Swedish Pulmonary Arterial Hypertension Registry; SvO₂=mixed venous oxygen saturation; WHO=World Health Organization; WSPH=World Symposium on Pulmonary Hypertension.

References: 1. Humbert M, et al. Eur Heart J. 2022;43(38):3618-3731. 2. Benza RL, et al. Circulation. 2010;122(2):164-172. 3. Hoeper MM, et al. Eur Respir J. 2017;50(2):1700740. 4. Kylhammar D, et al. Eur Heart J. 2018;39(47):4175-4181. 5. Boucly A, et al. Eur Respir J. 2017;50(2):1700889. 6. Benza RL, et al. Chest. 2019;156(2):323-337. 7. Dardi F, et al. Eur Respir J. 2024;64(4):2401323. 8. Bouzina H, et al. ESC Heart Fail. 2021;8(1):680-690. 9. Galiè N, et al. Eur Respir J. 2019;53(1):1801889. 10. Benza RL, et al. Chest. 2021;159(1):337-346.