CurrentCignaPolicy IP0631

Endothelin Receptor Antagonists

This policy governs medical necessity and coverage criteria for endothelin receptor antagonists (ambrisentan, macitentan, macitentan/tadalafil combination, and bosentan) for treatment of pulmonary arterial hypertension (WHO Group 1) and selected other uses (CTEPH, systemic sclerosis digital ulcers) for Cigna-administered health plans.

Policy Summary

PayerCigna

PolicyEndothelin Receptor Antagonists

Policy CodePolicy IP0631

Change TypeMaterial updates and additions

Effective DateDec 15, 2024

Next Review DateN/A

Key ActionObtain prior authorization and document right heart catheterization confirmation of WHO Group 1 PAH; initial approvals are generally for 1 year when criteria are met.

SourceLink

POLICY UPDATE CHANGES

Opsynvi (macitentan/tadalafil) was added to the policy with preferred product criteria requirements and guidance for initiation/transition.

Clarified PAH confirmation requirement to require right heart catheterization (echocardiogram removed as an option) and separated 'Initial Therapy' versus 'Currently Receiving' pathways.

New criteria added allowing bosentan (Tracleer/generic) for CTEPH when Adempas is tried or contraindicated, and for systemic sclerosis digital ulcers after trial of CCB or PDE5 inhibitor.

Policy adds a contraindication/Not Covered statement for concurrent use of Opsynvi with guanylate cyclase stimulators (e.g., riociguat).

4products listed

1 yeartypical approval duration

RHCdiagnostic confirmation

CTEPH/digital ulcersother supported indications

Coverage Criteria and Indications

Initial and ongoing therapy for WHO Group 1 PAH

Covered when ONE of the following is met; approvals typically for 1 year.

PAH coverage pathways

A) Initial Therapy
- Patient has a diagnosis of World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH).
- Patient meets BOTH of the following: (a) Patient has had a right heart catheterization; and (b) results of the right heart catheterization confirm the diagnosis of WHO Group 1 PAH.
- The medication is prescribed by or in consultation with a cardiologist or a pulmonologist.
- Preferred product criteria is met for the product(s) as listed in the policy tables.
B) Patient is Currently Receiving the Requested Endothelin Receptor Antagonist or Opsynvi
- Patient has a diagnosis of World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH).
- Patient meets BOTH of the following: (a) Patient has had a right heart catheterization; and (b) results of the right heart catheterization confirm the diagnosis of WHO Group 1 PAH.
- The medication is prescribed by or in consultation with a cardiologist or a pulmonologist.

CTEPH (bosentan)

Approve bosentan for CTEPH for 1 year when ALL of the following are met:

CTEPH bosentan criteria

A) Prior therapy or current bosentan
- Patient has tried Adempas (riociguat).
- According to the prescriber, use of Adempas is contraindicated (examples include concurrent use of nitrates or nitric oxide donors, use of phosphodiesterase inhibitors, hypotension or risk for hypotension).
- Patient is currently receiving bosentan (Tracleer or generic).
The medication is prescribed by or in consultation with a cardiologist or a pulmonologist.

Digital ulcers in systemic sclerosis (bosentan)

Approve bosentan for digital ulcers in systemic sclerosis for 1 year when the following are met:

Digital ulcers criteria

Prior vasodilator trial
- Patient has tried one calcium channel blocker (examples include amlodipine, felodipine, nifedipine).
- Patient has tried one phosphodiesterase type 5 (PDE5) inhibitor (examples include sildenafil, tadalafil, vardenafil).
Preferred product criteria is met for the product(s) as listed in the policy tables.

Any use of ambrisentan (Letairis, generic), Opsumit, or bosentan (Tracleer, generic) that is not specifically listed in this policy is considered experimental, investigational, or unproven. This includes indications and treatment situations for which there is not sufficient published evidence to support clinical benefit; the policy will be updated as new data become available.

Uses of these endothelin receptor antagonists beyond the indications explicitly covered in this policy (WHO Group 1 PAH; bosentan for CTEPH; bosentan for systemic sclerosis-related digital ulcers) are considered not medically necessary/experimental unless and until supported by peer-reviewed evidence and added to the policy. Providers seeking coverage for off-label or other supportive-evidence uses should be prepared to provide clinical trial data or peer-reviewed literature demonstrating efficacy for the requested indication.

Billing and Diagnostic Codes

Prior authorization affected codesmixed

affected codes

Placeholder in policy indicating prior authorization may be required for some products and codes

Hemodynamic diagnostic thresholds — right heart catheterization values

Mean pulmonary artery pressure (mPAP)mPAP > 20 mmHg (at rest)

Pulmonary arterial wedge pressure (PAWP)PAWP ≤ 15 mmHg

Pulmonary vascular resistance (PVR)PVR > 2 Wood units (measured by cardiac catheterization)

Prior Authorization, Documentation, and Prescriber Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Initial approvals are generally for 1 year when criteria are met. Ensure the prescriber documents specialty and supporting clinical evidence as described below.

Documentation Required

Required documentation for PAH

Required documentation for PAH: patient must have WHO Group 1 PAH confirmed by right heart catheterization. Include documentation that a right heart catheterization was performed and the results that confirm WHO Group 1 PAH. The request must indicate the medication is prescribed by or in consultation with a cardiologist or pulmonologist. Include any supporting clinical notes (e.g., hemodynamic measurements, diagnostic reports) and evidence that preferred product criteria are met or that patient is currently receiving the requested endothelin receptor antagonist or Opsynvi when applicable.

Right heart catheterization report confirming WHO Group 1 PAH

Clinical Background

Pulmonary arterial hypertension (PAH, WHO Group 1) is a progressive disorder characterized by elevated pulmonary arterial pressures and vascular resistance that impair exercise capacity and can lead to right heart failure. Diagnosis requires invasive hemodynamic confirmation by right heart catheterization with thresholds of mean pulmonary arterial pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance > 2 Wood units. Endothelin receptor antagonists (ambrisentan, macitentan, macitentan/tadalafil combination, and bosentan) are oral therapies used to improve exercise tolerance and delay clinical worsening in WHO Group 1 PAH and may be used alone or in combination with other PAH-targeted agents.

Key Definitions and Terms

PAH — Pulmonary arterial hypertension (short facts)

DefinitionPulmonary arterial hypertension (PAH) — Group 1 pulmonary hypertension; progressive narrowing of small pulmonary arteries causing elevated pulmonary arterial pressures and impaired exercise capacity.

Diagnostic confirmationDiagnosis requires right heart catheterization with mPAP > 20 mmHg, PAWP ≤ 15 mmHg, and PVR > 2 Wood units.

Typical clinical goalMedications (endothelin receptor antagonists, PDE5 inhibitors, combination therapy) aim to improve exercise ability and delay clinical worsening.

Affected populationRare condition with fewer than 20,000 patients in the U.S.; mean age of diagnosis 36–50 years but can affect any age.

CTEPH — Chronic thromboembolic pulmonary hypertension (short facts)

Definition

Policy Summary

PayerCigna

PolicyEndothelin Receptor Antagonists

Policy CodePolicy IP0631

Change TypeMaterial updates and additions

Effective DateDec 15, 2024

Next Review DateN/A

Key ActionObtain prior authorization and document right heart catheterization confirmation of WHO Group 1 PAH; initial approvals are generally for 1 year when criteria are met.

SourceLink

On This Page

Preferred product criteria is met for the product(s) as listed in the policy tables.

Prescriber specialty (cardiologist or pulmonologist) or documentation of consultation

Clinical supporting documentation: hemodynamics, diagnostic reports, prior therapies

If continuation: documentation of current use of requested endothelin receptor antagonist or Opsynvi

Documentation Required

Required documentation for CTEPH

Required documentation for CTEPH: include documentation of diagnosis and prescriber specialty (cardiologist or pulmonologist). For bosentan (Tracleer) approval, provide documentation that the patient has tried Adempas (riociguat) or that Adempas is contraindicated per the prescriber (examples: concurrent nitrates or nitric oxide donors, concurrent PDE5 inhibitor use, hypotension or risk for hypotension), or documentation that the patient is currently receiving bosentan. Include supporting clinical notes and any relevant prior therapy records.

Documentation of CTEPH diagnosis
Prescriber specialty (cardiologist or pulmonologist) or documentation of consultation
Evidence of trial of Adempas OR documented contraindication to Adempas (e.g., concurrent nitrates or PDE5 inhibitors, hypotension) OR documentation of current bosentan use
Supporting clinical notes and prior therapy records

Step Therapy

Step therapy requirements for bosentan

Step therapy for bosentan (Tracleer): approve for 1 year when the patient meets criteria and ONE of the following is documented: trial of Adempas (riociguat) with lack of response or intolerance; or prescriber documents a contraindication to Adempas (examples include concurrent use of nitrates/nitric oxide donors, concurrent phosphodiesterase-5 inhibitors such as sildenafil or tadalafil, or hypotension/at risk for hypotension); or the patient is currently receiving bosentan. Include documentation of the trial, intolerance, or contraindication in the prior authorization request.

Documented trial of Adempas (riociguat) OR
Documented contraindication to Adempas (e.g., concurrent nitrates/nitric oxide donors, concurrent PDE5 inhibitors, hypotension) OR
Documentation that patient is currently receiving bosentan (Tracleer)

Denial Risk

Contraindicated combination

Contraindicated combinations: concurrent use of Opsynvi (macitentan/tadalafil) with guanylate cyclase stimulators (e.g., riociguat/Adempas) is contraindicated and should be avoided. Document prior to approval if there is any concurrent or planned use of these agents.

Opsynvi + guanylate cyclase stimulators (e.g., riociguat) — contraindicated

Chronic thromboembolic pulmonary hypertension (CTEPH) — persistent obstruction of pulmonary arteries, often a complication of pulmonary embolism (classified as Group 4 pulmonary hypertension).

Preferred therapyPulmonary endarterectomy is the treatment of choice for most patients; medical therapy is an option when inoperable (≈40% of patients may be inoperable).

Common symptomsProgressive dyspnea on exertion, fatigue, syncope, hemoptysis, and signs of right heart failure.

Adjunctive careAnticoagulant therapy is typically given; medical therapy (e.g., bosentan per policy) may be used in selected patients.