PAH Facts

SETTING AND TRACKING YOUR PAH PATIENT GOALS

The 2022 ESC/ERS Guidelines recommend follow-up assessments every 3 to 6 months for stable patients with PAH.² Since PAH can progress rapidly, it is critical to monitor your patients often.³

ERS=European Respiratory Society; ESC=European Society of Cardiology; PAH=pulmonary arterial hypertension; WHO=World Health Organization.

ASSESS AND MONITOR PATIENT RISK STATUS (3-STRATA MODEL)²

In the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, risk assessment of PAH patients is split into 2 treatment models—an updated 3-strata model, which is recommended for assessing risk at diagnosis, and the newer 4-strata model, which is recommended for assessing risk at follow-up. The 3-strata model, shown in the chart directly below, can help determine treatment escalation, risk assessment, and general treatment strategies.

Select a risk level:

Low Risk

Intermediate Risk

High Risk

Table to assess patient low risk status (3-Strata Model)

Table to assess patient Intermediate risk status (3-Strata Model)

Table to assess patient high risk status (3-Strata Model)

The guidelines above can assist with:

Creating goals and monitoring progress to help guide the course of treatment
Setting goals for your PAH patients that include exercise capacity (6MWD), WHO functional class, and hemodynamics

6MWD=6-minute walk distance;

BNP=brain natriuretic peptide;

CI=cardiac index;

cMRI=cardiac magnetic resonance imaging;

CPET=cardiopulmonary exercise testing;

HF=heart failure;

NT-proBNP=N-terminal pro-brain natriuretic peptide;

PAH=pulmonary arterial hypertension; pred.=predicted;

RA=right atrium;RAP=right atrial pressure;

RVEF=right ventricular ejection fraction;

RVESVI=right ventricular end-systolic volume index;

sPAP=systolic pulmonary arterial pressure;

SVI=stroke volume index;

SvO₂=mixed venous oxygen saturation;

TAPSE=tricuspid annular plane systolic excursion;

VE/VCO₂=ventilatory equivalents for carbon dioxide;

VO₂=oxygen consumption;

WHO FC=World Health Organization Functional Class.

^aOccasional syncope during heavy exercise or occasional orthostatic syncope in a stable patient.

^bRepeated episodes of syncope even with little or regular physical activity.

^cObserve that 6MWD is dependent upon age, height, and burden of comorbidities.

^dTo harmonize with the four-strata model shown in Table 18, the BNP and NT-proBNP cut-off levels have been updated from the 2015 version based on data from the REVEAL registry, acknowledging that the European validation studies have used the original cut-off levels.

^ecMRI parameters adapted from the 2022 ESC/ERS guidelines.

2022 ESC/ERS GUIDELINES: 4-STRATA RISK-ASSESSMENT TOOL (FOLLOW-UP)²

The 4-strata (low, intermediate-low, intermediate-high, and high risk) model is based on WHO FC, 6MWD, and BNP or NT-proBNP, which is recommended for assessing risk at follow-up; additional variables should be considered as needed (eg, right heart imaging, hemodynamics). At any stage, individual factors (eg, age, sex, disease type, comorbidities, kidney function) should also be considered.

Select a risk level:

Low Risk

Intermediate-Low Risk

Intermediate-High Risk

High Risk

4 Strata Risk Assessment Table containing determinants of prognosis vs Low risk

4 Strata Risk Assessment Table containing determinants of prognosis vs Intermediate low risk

4 Strata Risk Assessment Table containing determinants of prognosis vs Intermediate-high risk

4 Strata Risk Assessment Table containing determinants of prognosis vs High Risk

DOWNLOAD THE ADAPTED ESC/ERS GUIDELINES FOR PAH

Icon of an open dictionary with a book mark

CLINICAL DEFINITION

PAH is defined as a mean pulmonary artery pressure (mPAP) >25 mm Hg with a pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg measured by cardiac catheterization.³

TREATMENT LANDSCAPE

The REVEAL Registry evaluated 2525 patients, of whom 2438 were on PAH treatment with ERAs, PCAs, or PDE-5 inhibitors. More than 50% of these patients remained in WHO functional class III or IV.⁴

Evaluation for etiologies other than PAH is appropriate in all instances.
To rule out CTEPH (WHO Group 4), a V/Q scan should be performed.^3,5

CTEPH=chronic thromboembolic pulmonary hypertension; ERA=endothelin receptor antagonist; PCA=prostacyclin analog; PDE-5=phosphodiesterase type 5; V/Q=ventilation/perfusion.

WHO GROUP CLASSIFICATION^1,6

Identify which WHO group your PH patients are in.

I. PAH

II. PH due to left heart disease

III. PH due to lung disease and/or hypoxia

IV. CTEPH

V. PH with unclear multifactorial mechanisms

Adempas is approved for adults with PAH (WHO Group 1) and inoperable or persistent/recurrent CTEPH (WHO Group 4) after surgery. Adempas has been studied predominantly in WHO functional class II-III patients.¹

PH=pulmonary hypertension

DOWNLOAD THE ADAPTED ESC/ERS GUIDELINES FOR PAH

CLINICAL DEFINITION

PAH is defined as a mean pulmonary artery pressure (mPAP) >25 mm Hg with a pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg measured by cardiac catheterization.³

TREATMENT LANDSCAPE

The REVEAL Registry evaluated 2525 patients, of whom 2438 were on PAH treatment with ERAs, PCAs, or PDE-5 inhibitors. More than 50% of these patients remained in WHO functional class III or IV.⁴

Evaluation for etiologies other than PAH is appropriate in all instances.
To rule out CTEPH (WHO Group 4), a V/Q scan should be performed.^3,5

CTEPH=chronic thromboembolic pulmonary hypertension; ERA=endothelin receptor antagonist; PCA=prostacyclin analog; PDE-5=phosphodiesterase type 5; V/Q=ventilation/perfusion.

WHO GROUP CLASSIFICATION^1,2,6

Identify which WHO group your PH patients are in.

I. PAH

II. PH associated with left heart disease

III. PH associated with lung disease and/or hypoxia

IV.I CTEPH

V. PH with unclear and/or multifactorial mechanism

PH=pulmonary hypertension.

MORE IMPORTANT SAFETY INFORMATION LESS IMPORTANT SAFETY INFORMATION

Important Safety Information and Indications

WARNING: EMBRYO-FETAL TOXICITY

Do not administer Adempas (riociguat) tablets to a pregnant female because it may cause fetal harm.

Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and one month after stopping treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment.

For all female patients, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program.

Contraindications

Adempas is contraindicated in:

Pregnancy. Based on data from animal reproduction studies, Adempas may cause fetal harm when administered to a pregnant woman and is contraindicated in females who are pregnant. Adempas was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form.
Concomitant administration with specific phosphodiesterase (PDE)-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) or nonspecific PDE inhibitors (such as dipyridamole or theophylline) is contraindicated. Do not administer within 24 hours of sildenafil. Do not administer 24 hours before or within 48 hours after tadalafil.
Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators.
Patients with Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (PH-IIP).

Warnings and Precautions

Embryo-Fetal Toxicity. Based on data from animal reproduction studies, Adempas may cause embryo-fetal toxicity when administered to a pregnant female and is contraindicated in females who are pregnant. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment, monthly during treatment, and for one month after stopping treatment. Advise females of reproductive potential to use effective contraception during treatment with Adempas and for at least one month after the last dose.

For females, Adempas is only available through a restricted program under the Adempas REMS Program.

Adempas REMS Program. Females can only receive Adempas through the Adempas REMS Program, a restricted distribution program.

Important requirements of the Adempas REMS Program include the following:

Prescribers must be certified with the program by enrolling and completing training.
All females, regardless of reproductive potential, must enroll in the Adempas REMS Program prior to initiating Adempas. Male patients are not enrolled in the Adempas REMS Program.
Female patients of reproductive potential must comply with the pregnancy testing and contraception requirements.
Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive Adempas.

Further information, including a list of certified pharmacies, is available at www.AdempasREMS.com or 1-855-4ADEMPAS.

Hypotension. Adempas reduces blood pressure. Consider the potential for symptomatic hypotension or ischemia in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or concomitant treatment with antihypertensives or strong CYP and P-gp/BCRP inhibitors. Consider a dose reduction if patient develops signs or symptoms of hypotension.

Bleeding. In the placebo-controlled clinical trials, serious bleeding occurred in 2.4% of patients taking Adempas compared to 0% of placebo patients. Serious hemoptysis occurred in 5 (1%) patients taking Adempas compared to 0 placebo patients, including one event with fatal outcome. Serious hemorrhagic events also included 2 patients with vaginal hemorrhage, 2 with catheter-site hemorrhage, and 1 each with subdural hematoma, hematemesis, and intra-abdominal hemorrhage.

Pulmonary Veno-Occlusive Disease. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Therefore, administration of Adempas to such patients is not recommended. Should signs of pulmonary edema occur, the possibility of associated PVOD should be considered and if confirmed, discontinue treatment with Adempas.

Most Common Adverse Reactions

The most common adverse reactions occurring more frequently (≥3%) on Adempas than placebo were headache (27% vs 18%), dyspepsia/gastritis (21% vs 8%), dizziness (20% vs 13%), nausea (14% vs 11%), diarrhea (12% vs 8%), hypotension (10% vs 4%), vomiting (10% vs 7%), anemia (7% vs 2%), gastroesophageal reflux disease (5% vs 2%), and constipation (5% vs 1%).

Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were palpitations, nasal congestion, epistaxis, dysphagia, abdominal distension, and peripheral edema.

Indications

Adempas (riociguat) is indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
Adempas is indicated for the treatment of adults with pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.*

Efficacy was shown in patients on Adempas monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominantly patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%).

^*Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of pulmonary hypertension, start of new PAH-specific treatment, persistent decrease in 6MWD, and persistent worsening of WHO functional class.

For important risk and use information, please see the full Prescribing Information, including Boxed Warning.

References:

Adempas Prescribing Information. Whippany, NJ. Bayer Pharmaceuticals Inc., 2021.
Humbert M, Kovacs G, Hoeper M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;00:1-114.
McLaughlin VV, Archer SL, Badesch BD, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society Inc., and the Pulmonary Hypertension Association. Circulation. 2009;119(16):2250-2294.
Badesch DB, Raskob GE, Elliot CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-387.
Hoeper MM, Barberà JA, Channick RN, et al. Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S85-96.
Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34-D41.

Adempas is approved for adults with PAH (WHO Group 1) and has been studied predominantly in WHO functional class II-III patients.¹

WARNING: EMBRYO-FETAL TOXICITY

PAH FACTS

Adempas is approved for adults with PAH (WHO Group 1) and has been studied predominantly in WHO functional class II-III patients.1

WARNING: EMBRYO-FETAL TOXICITY

Adempas is approved for adults with PAH (WHO Group 1) and has been studied predominantly in WHO functional class II-III patients.¹