ModifiedPremera BluecrossPolicy 5.01.522

Advanced Therapies for Pharmacological Treatment of Pulmonary Arterial Hypertension

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Defines when specific advanced medications (oral, inhaled, IV/SC) for pulmonary arterial hypertension (PAH, WHO Group 1) may be considered medically necessary for Premera members and informs providers about coverage criteria and documentation expectations.

Policy Summary

PayerPremera Bluecross

PolicyAdvanced Therapies for Pharmacological Treatment of Pulmonary Arterial Hypertension

Policy CodePolicy 5.01.522

Change TypeReplaces prior PAH medication policies

Effective DateAug 1, 2026

Last ReviewJul 14, 2026

Next Review DateJul 14, 2026

Key ActionSubmit prior authorization with documentation of a PAH (WHO Group 1) diagnosis and, for combination therapy, evidence of inadequate response to a single medication and that agents are from different therapeutic classes.

SourceLink

POLICY UPDATE CHANGES

This policy (5.01.522) replaces prior policies 5.01.09 and 5.01.509.

2026-08-01Policy effective date

WHO Group 1Targeted condition

Failed single medCombo therapy rule

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ModifiedPremera BluecrossPolicy 5.01.522

Advanced Therapies for Pharmacological Treatment of Pulmonary Arterial Hypertension

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Policy Summary

PayerPremera Bluecross

PolicyAdvanced Therapies for Pharmacological Treatment of Pulmonary Arterial Hypertension

Policy CodePolicy 5.01.522

Change TypeReplaces prior PAH medication policies

Effective DateAug 1, 2026

Last ReviewJul 14, 2026

Next Review DateJul 14, 2026

SourceLink

POLICY UPDATE CHANGES

This policy (5.01.522) replaces prior policies 5.01.09 and 5.01.509.

2026-08-01Policy effective date

WHO Group 1Targeted condition

Failed single medCombo therapy rule

Distinct agents listed

InfusionsMedical benefit items

Coverage Criteria for PAH Therapies

Medical necessity for listed PAH therapies (initial and combination use)

Covered when ALL of the following are met

Primary coverage conditions: The individual has a diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1).

Policy specifies WHO Group 1; documented diagnosis required

Combination therapy conditions

Failed single‑agent response: Has failed to demonstrate an adequate response to a single medication (documented).
Clinical documentation of inadequate response required
Different therapeutic classes: Medications used in combination are from different therapeutic classes.
Requests for combinations from the same class are not supported

Prior authorization and documentation: Prior authorization is required and submission must include medical records documenting diagnosis, treatment history, and rationale for combination use when applicable.

Initial and re‑authorization approvals may be granted up to 12 months; see Coding/Authorization sections for required documentation

Medical necessity criteria for listed PAH medications

Covered when ALL of the following are met

Primary coverage criteria: The individual has a diagnosis of PAH, WHO Group 1.

Documented WHO Group 1 diagnosis required

Combination therapy requirements: When used as combination therapy, the individual has failed to demonstrate an adequate response to a single medication AND the medications are from different therapeutic classes.

Both subconditions must be met for combination therapy coverage

Agent applicability: Coverage applies to listed PAH medications and formulations (examples include tadalafil/Alyq/Tadliq, bosentan/Tracleer, epoprostenol/Flolan/Veletri, macitentan/Opusmit, treprostinil/Remodulin/Orenitram/Tyvaso/Yutrepia, sildenafil/Revatio, selexipag/Uptravi).

Agent list illustrative; refer to Table 1 for full benefit assignment

Initial and combination therapy criteria

Covered when ALL of the following are met

Main coverage conditions: 1) The individual has a diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1). 2) When the requested medication is used as combination therapy, BOTH: a) the individual has failed to demonstrate an adequate response to a single medication; AND b) the medications used in combination are from different therapeutic classes.N/A

Applies to listed agents such as tadalafil (Tadliq/Adcirca), treprostinil (Orenitram/Remodulin), epoprostenol (Flolan/Veletri), bosentan (Tracleer), macitentan (Opsumit), sildenafil (Revatio generics), selexipag (Uptravi), and others.

Prior authorization requirement: Prior authorization is required for listed therapies and combination regimens and will be evaluated against these criteria.

Providers must submit clinical documentation to support diagnosis and prior treatment history

General coverage rules for listed PAH agents

Covered when ALL of the following are met

Primary indication: The individual has a diagnosis of PAH, WHO Group 1.

Coverage limited to WHO Group 1 unless otherwise specified (see Adempas for CTEPH).

Monotherapy or combination: When used as combination therapy, medications must be from different therapeutic classes.

Policy emphasizes class-difference for combination regimens; same‑class combinations are not supported.

Combination therapy prerequisite: For many agent‑specific entries, combination therapy is allowed only after the individual has failed to demonstrate an adequate response to a single medication.

Documented inadequate response to monotherapy required for add‑on therapy in applicable entries.

Coverage criteria for listed PAH therapies

Covered when ALL of the following are met

Primary diagnosis: The individual has a diagnosis of PAH, WHO Group 1.

Documented diagnosis required for coverage of listed therapies.

Combination therapy conditions: When used as combination therapy, the following ALL must be met: has failed to demonstrate an adequate response to a single medication; and medications are from different therapeutic classes.

Applies only when combination therapy is being requested; prior clinical evidence required.

Covered agents examples: Examples of covered therapies include: Flolan (epoprostenol) IV infusion; Macitentan oral; Orenitram (treprostinil) oral; Sildenafil (Revatio generics) oral formulations; Tadliq/Alyq (tadalafil) oral; Treprostinil (SC/IV/inhaled/oral); Uptravi (selexipag).

Refer to Table 1 for complete listing and benefit assignment.

Coverage criteria for listed PAH therapies

Covered when ALL of the following are met

PAH diagnosis: The individual has a diagnosis of PAH, WHO Group 1.

Required across medication‑specific entries.

Combination therapy conditions: When used as combination therapy: the individual has failed to demonstrate an adequate response to a single medication AND the medications are from different therapeutic classes.

Both subconditions must be documented for combination therapy coverage.

Agent examples: Listed therapies subject to these criteria include (but are not limited to): bosentan, epoprostenol (Flolan/Veletri), macitentan, treprostinil (oral/SC/IV/inhaled), sildenafil formulations, tadalafil formulations, and selexipag (Uptravi).

Agent list repeated throughout the policy; see Coding Table for benefit application.

Initial and combination therapy coverage criteria

Covered for pulmonary arterial hypertension (PAH, WHO Group 1) when ALL of the following criteria are met:

Primary coverage criteria: The individual has a diagnosis of PAH, WHO Group 1.

Supported across multiple agent entries; RHC and clinical documentation expected per standard practice

Combination therapy criteria: When used as combination therapy, ALL of the following must be met: (1) Has failed to demonstrate an adequate response to a single medication; (2) Medications are from different therapeutic classes.

Combination therapy precondition; documentation must show treatment history and rationale

Covered agents: Therapies named include: Flolan (epoprostenol) IV infusion; Macitentan oral; Orenitram (treprostinil) oral; Sildenafil (10 mg/mL oral and 20 mg tablet); Tadliq (tadalafil) oral; Treprostinil SC/IV; Uptravi (selexipag).

Agent list illustrative; additional agents appear in Table 1

Combination therapy coverage criteria

Covered when ALL of the following are met

Main eligibility: The individual has a diagnosis of PAH, WHO Group 1.

Documented diagnosis required

Combination therapy conditions: When used as combination therapy, the individual has failed to demonstrate an adequate response to a single medication AND the medications are from different therapeutic classes.

Applies to combination therapy requests and must be documented

Coverage for listed PAH therapies

Covered when ALL of the following are met

Main coverage conditions: The individual has a diagnosis of PAH, WHO Group 1; when used as combination therapy, the individual has failed to demonstrate an adequate response to a single medication AND the medications are from different therapeutic classes.

Applies to listed agents such as Flolan, Macitentan, Orenitram, sildenafil generics, Tadliq, treprostinil formulations, Uptravi, Veletri, Bosentan, and others enumerated in this section.

Coverage for listed PAH medications

Covered when ALL of the following are met:

Primary diagnosis requirement: The individual has a diagnosis of PAH, WHO Group 1.

Required across the policy

Combination therapy requirement: When used as combination therapy, the individual has failed to demonstrate an adequate response to a single medication AND the medications are from different therapeutic classes.

Documentation of prior treatment failure and class‑difference required

Combination therapy (medical necessity)

Covered when ALL of the following are met for combination therapy

Combination therapy prerequisites: The individual has a diagnosis of PAH, WHO Group 1 AND has failed to demonstrate an adequate response to a single medication AND the medications used in combination are from different therapeutic classes.

Examples of medications across classes are listed in the policy (see Table 1); contraindicated combinations (e.g., riociguat + PDE5 inhibitors) must be avoided.

General PAH coverage criteria

Covered when ALL of the following are met for PAH (WHO Group 1) unless otherwise specified for a given agent

Diagnosis: The individual has a diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1).

Coverage limited to WHO Group 1 unless agent‑specific exceptions noted (e.g., riociguat for CTEPH).

Combination therapy requirements: When used as combination therapy, ALL of the following must be met: Has failed to demonstrate an adequate response to a single medication; Medications are from different therapeutic classes.

This requirement is repeated across multiple agent‑specific sections; documentation of prior therapy and rationale required.

Adempas (riociguat) for CTEPH

Adempas (riociguat) — CTEPH (WHO Group 4)

Indication: The individual is diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH, WHO Group 4).

Adempas (riociguat) is FDA‑approved for CTEPH

Surgical candidacy: One of the following must be met: is not a surgical candidate; has inoperable CTEPH; or has recurrent or persistent CTEPH after surgical treatment.

Medical therapy recommended when pulmonary endarterectomy is contraindicated or residual PH persists post‑surgery

Brand vs generic step requirements

Brand-specific criteria where noted (examples)

Ambrisentan (Letairis) brand step: Has tried and had an inadequate response or intolerance to generic ambrisentan before Letairis; when used in combination, meets combination therapy requirements.

Letairis may be first‑line in combination with tadalafil for treatment‑naïve PAH FC II or III when criteria met (AMBITION evidence cited).

Macitentan (Opsumit) brand step: Has tried and had an inadequate response or intolerance to generic macitentan before Opsumit; when used in combination, meets combination therapy requirements.

Agent‑specific brand step examples from policy entries

Treprostinil (Remodulin/brand products): Has tried and had an inadequate response or intolerance to generic treprostinil injection (SC or IV) before brand products; when used in combination, meets combination therapy requirements.

Policy lists prior trial/intolerance to generic formulations as a step for some branded agents.

Yutrepia coverage criteria

Yutrepia (treprostinil inhalation powder) specific criteria

Indication and severity: Is experiencing signs and symptoms of WHO functional class II, III, or IV.

Yutrepia intended for symptomatic individuals per agent‑specific entry

Hemodynamics: Has pulmonary vascular resistance (PVR) >= 5 Wood units AND pulmonary capillary wedge pressure (PCWP) <= 15 mmHg from right heart catheterization.PVR >= 5 Wood units; PCWP <= 15 mmHg

RHC‑derived hemodynamics required for Yutrepia per policy; cite RHC values

Prior therapy: Has tried and had an inadequate response to an endothelin receptor antagonist AND a phosphodiesterase‑5 inhibitor OR a soluble guanylate cyclase (sGC) stimulator.

Documented prior trials required before Yutrepia initiation

Winrevair coverage criteria

Winrevair (sotatercept‑csrk) specific criteria

Age: Individual is aged 18 years or older.>= 18 years

Per agent‑specific entry in policy

Diagnosis: Diagnosed with PAH, WHO Group 1.

Coverage limited to adult PAH (WHO Group 1) for Winrevair per policy

Benefit Application / Table of Therapies

Benefit assignment and therapies listed for PAH (WHO Group 1).

Benefit assignment: Specific agents are managed under the medical or pharmacy benefit as listed: Flolan (epoprostenol), generic treprostinil, Remodulin (treprostinil), Uptravi (selexipag), and Veletri (epoprostenol) are managed under the medical benefit; many oral agents (e.g., riociguat, tadalafil/Alyq/Tadliq, ambrisentan/Letairis, macitentan/Opsumit, Orenitram, sildenafil/Revatio, bosentan/Tracleer, Tyvaso, Yutrepia) are managed under the pharmacy benefit; Winrevair is managed under both benefits.

See Table 1 for the full enumeration of therapies and benefit application

Covered clinical scenarios

Coverage stance and when therapies are considered medically necessary

Indication scope: Therapies are intended for individuals with PAH (WHO Group 1) or CTEPH (WHO Group 4) as appropriate to the drug's FDA‑approved indication.

Riociguat is FDA‑approved for CTEPH; most other advanced therapies target PAH

Benefit application: Specific agents are assigned to the medical or pharmacy benefit as listed (e.g., Flolan and Remodulin under medical; riociguat and tadalafil under pharmacy; Winrevair under both).

Refer to Benefit Application/Table 1 for details

Combination therapy role: For individuals with inadequate response to monotherapy, add‑on combination therapy using two FDA‑approved drug classes for PAH is supported by RCTs and meta‑analyses and may be covered when clinically indicated.

Meta‑analyses and RCTs (e.g., AMBITION) support add‑on and some initial combination strategies; contraindicated combinations (riociguat + PDE5 inhibitors) must be avoided

Clinical evidence supporting monotherapy

Evidence summary and implication for coverage decisions

Evidence-supported effects: Meta‑analyses and randomized trials demonstrate improved 6‑minute walk distance (6MWD) across prostanoids, endothelin receptor antagonists, and PDE5 inhibitors and show clinical benefit for monotherapy; prostanoids showed some low‑strength evidence for mortality reduction in pooled analyses.

AHRQ and other meta‑analyses summarized in policy; magnitudes of benefit vary by class and trial population

Combination therapy evidence: RCTs and meta‑analyses support add‑on combination therapy reducing clinical worsening and hospitalizations compared with monotherapy; initial combination (eg, ambrisentan + tadalafil in AMBITION) reduced clinical failure in the primary analysis set.

Evidence limitations include composite endpoints and variable trial designs; document clinical rationale when using combinations

Evidence caveats and applicability

Population and trial‑specific modifiers

Severity‑dependent applicability: Mortality reductions in pooled analyses appear concentrated in trials with higher baseline mortality or inclusion of WHO functional class IV individuals; caution is advised when generalizing survival benefit to lower‑risk populations.

Meta‑analyses note mortality benefit driven by sicker cohorts

Trial limitations: Evidence limitations include short median trial duration (eg, ~12 weeks in many RCTs), heterogeneous populations across studies, and sensitivity of some trial results (eg, oral treprostinil) to analytic methods and missing data handling.

Consider trial context when applying evidence to coverage decisions

Administration-route criteria

Route-specific considerations affecting coverage and utilization

Infused prostanoids requirements: Intravenous/subcutaneous prostanoid therapy requires documentation of the multi‑step initiation process (initial dose‑ranging, central venous access and pump plan) and ongoing maintenance strategy due to risks of catheter‑related complications and rebound pulmonary hypertension if infusion stops.

Epoprostenol and treprostinil infusion logistics affect authorization and benefit application (medical benefit); backup pump often required

Inhaled prostanoids and devices: Inhaled formulations require specialized dispensing devices and have specific quantity limits (eg, Tyvaso DPI, Yutrepia) and adverse effects (cough, throat irritation) that should be documented and considered in utilization decisions.

Policy lists device/quantity limits and notes device‑related dispensing requirements

Oral prostanoid considerations: Oral treprostinil demonstrated modest short‑term improvement in 6MWD in FREEDOM‑M but trial results are sensitive to analytic approach; adverse events and limited effect size may influence decisions about monotherapy versus background/combination therapy.

Clinical utility debated; consider prior background therapy and individual patient factors

The policy limits coverage of the advanced PAH agents listed to patients with a confirmed diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1). Coverage for these therapies is described only for that diagnostic group; use for other WHO pulmonary hypertension groups or for unrelated indications is not addressed in these coverage criteria.

Within the extracted coverage criteria there is no explicit list of general exclusions presented; the document instead frames coverage by required diagnostic and combination-therapy conditions rather than enumerating standalone exclusions.

Beyond the implicit exclusion that therapies are intended for individuals with PAH (WHO Group 1), this excerpt does not present additional explicit exclusions for use of the listed agents.

The policy does not support combination regimens in which the concomitant medications are from the same therapeutic class. For combination therapy to be considered, the agents must be from different therapeutic classes.

In this document segment there is no explicit exclusion list; coverage is defined by meeting the stated PAH (WHO Group 1) diagnosis and any applicable combination‑therapy conditions rather than by listing additional excluded clinical scenarios.

This portion of the policy does not state additional explicit exclusions; coverage determinations are driven by fulfillment of the specified diagnostic and combination‑therapy criteria.

Combination therapy is covered only when the patient has failed to demonstrate an adequate response to a single medication and the drugs added are from different therapeutic classes. The policy therefore does not support initiating combination regimens without documented prior inadequate response to monotherapy and class‑difference between agents.

No explicit exclusions are listed in this excerpt; authorization and coverage are contingent on meeting the policy’s diagnostic and combination‑therapy requirements.

This segment does not list explicit exclusions. Coverage is presented in terms of required conditions (e.g., PAH diagnosis, combination‑therapy prerequisites) rather than as an exclusions list.

No explicit exclusions are provided in this excerpt; the policy reiterates that coverage depends on meeting the specified PAH (WHO Group 1) and combination‑therapy conditions.

Within these chunks there are no explicit exclusions; the guidance focuses on eligibility criteria (diagnosis and combination‑therapy preconditions) that must be met for coverage.

The policy considers use of the listed advanced therapies for non‑PAH pulmonary hypertension (WHO Groups 2–5) to be investigational and excluded from coverage; riociguat (Adempas) and other agents are noted as appropriate only for their specified WHO group indications.

Yutrepia (treprostinil inhalation powder) includes specific clinical exclusions in its coverage criteria: individuals with uncontrolled systemic hypertension, left ventricular ejection fraction <45%, a history of untreated portal hypertension or liver disease, untreated obstructive sleep apnea, symptomatic coronary disease, or a platelet count <50,000/mm3 are excluded from receiving Yutrepia per the policy.

These chunks do not provide additional agent‑specific clinical exclusions. Instead, benefit assignment and management details (medical vs pharmacy benefit) are emphasized for listed therapies.

Evidence is limited regarding perioperative use of prostacyclin analogues, endothelin receptor antagonists, or riociguat for patients with operable CTEPH; the available studies are small and do not establish clear benefit, so perioperative use is not supported by sufficient evidence in this policy context.

The policy explicitly notes a contraindication: riociguat (Adempas) must not be used concurrently with phosphodiesterase type 5 inhibitors (for example, sildenafil, tadalafil, or vardenafil); concomitant use is contraindicated and should not be prescribed.

Introductory material and background information are informational and intended for providers; within these introductory excerpts there are no specific statements declaring particular services as not medically necessary.

In this excerpt there are no explicit ‘not medically necessary’ statements; instead the policy defines coverage by stating required diagnostic and combination‑therapy conditions that must be met.

Therapies subject to these criteria are considered not medically necessary when the individual does not have PAH (WHO Group 1), or when combination therapy is sought without documentation that the patient has failed to demonstrate an adequate response to a single medication or when the agents are from the same therapeutic class.

The policy does not support initiating combination therapy unless there is documentation that the patient has failed to demonstrate an adequate response to a single agent. Combination regimens started without this prior inadequate response are not supported by the coverage criteria.

Use of the listed agents for indications outside their specified WHO group approvals (for example, treating non‑PAH conditions) is not covered and is considered investigational according to the policy.

Combination therapy that does not meet the policy’s prerequisites (documented inadequate response to monotherapy and use of agents from different therapeutic classes) is not supported and would not meet coverage criteria.

Requests for combination therapy must include documentation of prior failure or inadequate response to a single medication and must show the proposed agents are from different therapeutic classes; combination therapy lacking this documentation is implied to not meet coverage requirements.

Combination therapy is not supported unless the individual has a diagnosis of PAH (WHO Group 1) and there is documented evidence of an inadequate response to single‑agent therapy with the added agents coming from different therapeutic classes.

The policy repeatedly requires documentation of failed/inadequate response to monotherapy and that concomitant agents be from different therapeutic classes; combination regimens that do not meet these conditions are not supported.

No additional ‘not medically necessary’ statements beyond the requirement to meet the WHO Group 1 diagnosis and the combination‑therapy documentation conditions are included in these excerpted chunks.

Within these chunks there are no explicit ‘not medically necessary’ declarations; the policy instead defines coverage by the diagnostic and combination‑therapy criteria to determine medical necessity.

Coding and Diagnostic Criteria

Listed PAH pharmacologic therapiesmixed

Alyq / tadalafil	Named product (tadalafil) referenced as Alyq and other tadalafil products (Tadliq, generic)
bosentan	Bosentan oral
Flolan / epoprostenol	Flolan (epoprostenol) IV infusion; Veletri (epoprostenol) also listed
macitentan	Macitentan oral
Orenitram / treprostinil	Orenitram (treprostinil) oral; treprostinil referenced generally
sildenafil	Sildenafil (generic for Revatio) in multiple formulations (10 mg/mL oral, 20 mg tablet) referenced
Uptravi / selexipag	Uptravi (selexipag)

Listed PAH medications and formulationsmixedCovered

tadalafil (Adcirca) - oral	tadalafil oral; generic of Adcirca
bosentan - oral	Bosentan oral
epoprostenol (Flolan/Veletri) - IV infusion	Flolan (epoprostenol) IV infusion; Veletri (epoprostenol) also listed
macitentan - oral	Macitentan oral
treprostinil (Orenitram) - oral	Orenitram (treprostinil) oral
sildenafil 10 mg/mL - oral solution	Sildenafil 10 mg/mL oral; generic of Revatio
sildenafil 20 mg - tablet	Sildenafil 20 mg tablet oral
selexipag (Uptravi) - oral	Uptravi (selexipag)
tadliq - (brand/formulation unspecified)	Tadliq

Listed medications and formulationsmixed

Tadliq (tadalafil)	listed oral therapy
Treprostinil (Orenitram/treprostinil)	oral formulation listed
Flolan (epoprostenol)	IV infusion formulation listed
Bosentan	oral endothelin receptor antagonist listed
Macitentan	oral endothelin receptor antagonist listed
Sildenafil 10 mg/mL - oral	oral liquid formulation listed; generic of Revatio
Sildenafil 20 mg - tablet	oral tablet formulation listed; generic of Revatio
Adcirca (tadalafil)	listed therapy name present in text

Medications referencedmixed

Bosentan	Bosentan oral
Flolan	Flolan (epoprostenol) IV infusion
Macitentan	Macitentan oral
Orenitram	Orenitram (treprostinil) oral
Sildenafil_10mg_per_mL	Sildenafil 10 mg/mL oral; generic of Revatio
Sildenafil_20mg_tablet	Sildenafil 20 mg tablet oral; generic of Revatio
Tadliq	Tadliq (tadalafil) oral
Treprostinil	Treprostinil (oral/SC/IV) formulations
Adcirca	Adcirca (tadalafil) oral
Uptravi	Uptravi (selexipag) — mentioned in section as covered under criteria

Listed PAH therapies in this sectionmixed

Bosentan	Bosentan oral
Flolan (epoprostenol)	Flolan (epoprostenol) IV infusion
Macitentan	Macitentan oral
Orenitram (treprostinil)	Orenitram (treprostinil) oral
Sildenafil 10 mg/mL	Sildenafil 10 mg/mL oral; generic of Revatio
Sildenafil 20 mg	Sildenafil 20 mg tablet oral; generic of Revatio
Tadliq (tadalafil)	Tadliq (tadalafil) oral
Treprostinil SC/IV	Treprostinil SC, IV
Uptravi (selexipag)	Uptravi (selexipag)

Listed medicationsNDC | drug namesCovered

Bosentan	oral
Flolan (epoprostenol)	IV infusion
Macitentan	oral
Orenitram (treprostinil)	oral
Sildenafil 10 mg/mL	oral; generic of Revatio
Sildenafil 20 mg	tablet oral; generic of Revatio
Tadliq (tadalafil)	oral
Treprostinil	SC, IV
Uptravi (selexipag)	oral

Listed agents (by product)NDC

NDC (multiple agents listed)

Flolan (epoprostenol) IV infusion; Macitentan oral; Orenitram (treprostinil) oral; Sildenafil 10 mg/mL oral; Sildenafil 20 mg tablet; Tadliq (tadalafil) oral; Treprostinil SC, IV; Uptravi (selexipag)

Listed medications and formulationsmixed

Sildenafil 10 mg/mL	oral; generic of Revatio
Sildenafil 20 mg	tablet oral; generic of Revatio
Tadliq	tadalafil oral
Treprostinil	SC, IV, and oral formulations (Orenitram)
Uptravi	selexipag oral, IV
Flolan / epoprostenol	IV infusion
Macitentan	oral
Veletri	epoprostenol IV formulation

Coding table (document placeholder)mixed

No codes listed

HCPCS / J-codesHCPCS

J1325	Injection, epoprostenol (use to report: Flolan and Veletri), 0.5 mg
J3285	Injection, treprostinil (use to report: Remodulin), 1 mg
J3490	Unclassified Drugs (Use to report: Uptravi and Yutrepia)
J3590	Unclassified biologics (use to report: Winrevair)
J7686	Treprostinil (Tyvaso), inhalation solution, FDA-approved final product, noncompounded, administered through DME, unit dose form, 1.74 mg
K0455	Infusion pump used for uninterrupted parenteral administration of medication (e.g. epoprostenol or treprostinil)
Q4074	Iloprost, inhalation solution, FDA-approved final product, noncompounded, administered through DME, up to 20 mcg (code termed 04/01/2026)

Medical benefit billing notesmixed

HCPCS

Infusion pumps and home infusion therapy may be billed through medical benefit HCPCS codes (specific codes referenced in Coding section).

Therapies by benefitmixed

NDC / drug list

List of agents (e.g., riociguat, tadalafil, ambrisentan, bosentan, sildenafil, treprostinil, selexipag, epoprostenol, sotatercept) managed under pharmacy or medical benefit as specified.

Combination therapy precondition — Failure to demonstrate adequate response to a single medication

Requirement before adding a second agentHas failed to demonstrate an adequate response to a single medication prior to approval of combination therapy

Therapeutic class requirementMedications used in combination must be from different therapeutic classes

Diagnosis requirementIndividual must have a diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1)

Documentation expectationMedical record must document inadequate response to prior single-agent therapy when combination therapy is requested

Prior Authorization, Documentation, and Billing Guidance

Prior Authorization

Prior authorization required for listed PAH medications

Prior authorization is required for advanced PAH therapies listed in the policy and will be evaluated against the policy criteria; approval requires documentation that the individual has PAH (WHO Group 1).

Prior Authorization

PAH prior authorization — WHO Group 1 and combo prerequisites

Requests for listed PAH medications require prior authorization and approval is contingent on a documented diagnosis of PAH (WHO Group 1); for combination regimens, documentation of prior inadequate response to single‑agent therapy and that agents are from different therapeutic classes is required.

Prior Authorization

Prior authorization — criteria for listed therapies

Prior authorization must be submitted for the advanced therapies enumerated; authorization is granted only when the individual meets PAH (WHO Group 1) diagnostic criteria and, for combination therapy, evidence of failure/inadequate response to a single medication plus different therapeutic classes is documented.

Background and Evidence Summary

BACKGROUND: Pulmonary arterial hypertension (PAH) is elevated pressure in the pulmonary arteries caused by narrowing or obstruction of small pulmonary arteries, increasing right‑heart workload and potentially progressing to right heart failure. Definitive diagnosis typically requires right heart catheterization and hemodynamic measurements. Treatment selection is guided by underlying cause, disease severity, and the distinct mechanisms of available drug classes; this policy specifies when targeted PAH therapies are medically necessary.

PAH, defined as World Health Organization Group 1 pulmonary hypertension, is the population for whom the policy’s listed advanced therapies may be considered medically necessary. The policy consistently requires a documented diagnosis of PAH (WHO Group 1) to meet coverage criteria.

Combination therapy, as used by this policy, denotes concurrent use of more than one PAH‑targeted medication. Coverage of combination regimens requires that the patient has failed to demonstrate an adequate response to a single medication and that the combined agents are from different therapeutic classes.

The policy reiterates that coverage applies only to individuals with a documented diagnosis of PAH (WHO Group 1); treatments for other WHO groups are not the primary population described for these therapies.

Coverage of the listed advanced therapies requires a documented diagnosis of PAH, WHO Group 1. Requests must demonstrate that the individual meets this diagnostic requirement to be considered medically necessary.

The policy includes agent‑specific criteria (for example, Yutrepia and Winrevair) within the PAH, WHO Group 1 population; such agents are covered only when both the general PAH coverage rules and any drug‑specific criteria are satisfied.

Definitions and Clinical Terms

inv-131: PAH, WHO Group 1 — Pulmonary arterial hypertension classified as WHO Group 1; policy population

DefinitionPulmonary arterial hypertension (PAH) classified as World Health Organization (WHO) Group 1 — the population for which listed therapies are considered medically necessary.

Coverage scopePolicy coverage and criteria apply specifically to PAH, WHO Group 1; use for other WHO groups requires separate review or is investigational for some agents.

DocumentationRequests must document the diagnosis of PAH (WHO Group 1) to meet coverage criteria.

inv-132: Combination therapy (as used here) — definition: concurrent use requiring prior inadequate response and different classes

DefinitionConcurrent use of more than one PAH-targeted medication; coverage requires prior documented inadequate response to a single medication before adding a second agent.

Policy Revision History

2026-08-01policy_effectiveLatest

New consolidated policy 5.01.522 became effective; it replaces prior policies 5.01.09 and 5.01.509.

2026-07-14policy_revision

Policy 5.01.522 was last revised (document header shows last revised date), finalizing consolidation and superseding earlier PAH medication policies.

Policy Summary

PayerPremera Bluecross

PolicyAdvanced Therapies for Pharmacological Treatment of Pulmonary Arterial Hypertension

Policy CodePolicy 5.01.522

Change TypeReplaces prior PAH medication policies

Effective DateAug 1, 2026

Last ReviewJul 14, 2026

Next Review DateJul 14, 2026

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Concomitant therapy: Will continue current PAH treatments unless not tolerated.

Policy expects continuation of background PAH therapy

Exclusion conditions: Does not have uncontrolled systemic hypertension, LVEF <45%, history of untreated portal hypertension/liver disease/untreated OSA/symptomatic coronary disease, or platelet count <50,000/mm^3.

These are agent‑specific exclusion criteria for Yutrepia

Initial combination therapy with two drug classes (example: ambrisentan plus tadalafil per AMBITION) is supported by evidence and may be covered when clinically appropriate.

Consider trial limitations and patient selection in applying initial combination therapy

CTEPH surgical candidacy: Pulmonary endarterectomy is standard of care for operable CTEPH; medical therapy (eg, riociguat) is recommended when endarterectomy is contraindicated or when pulmonary pressures remain elevated after surgery.

Surgical candidacy determines appropriateness of riociguat for CTEPH

Pulmonary vascular resistance (PVR) — >= 5 Wood units

PVR threshold for Yutrepia and PAH hemodynamicsPulmonary vascular resistance (PVR) ≥ 5 Wood units as measured by right heart catheterization

Measurement methodPVR must be obtained from right heart catheterization (RHC)

Context of useRequired for Yutrepia (treprostinil inhalation powder) coverage along with other criteria

Pulmonary capillary wedge pressure (PCWP) — <= 15 mmHg

PCWP threshold for Yutrepia and PAH hemodynamicsPulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg as measured by right heart catheterization

Measurement methodPCWP must be obtained from right heart catheterization (RHC)

Context of useRequired for Yutrepia (treprostinil inhalation powder) coverage along with other criteria

Hemodynamic diagnostic threshold — Mean pulmonary arterial pressure ≥ 25 mm Hg

Diagnostic mean PAP thresholdMean pulmonary arterial pressure ≥ 25 mm Hg confirms pulmonary hypertension by right heart catheterization

Diagnostic methodDiagnosis is usually made following measurement by right heart catheterization

Clinical implicationMean PAP ≥ 25 mm Hg used to define pulmonary hypertension and guide eligibility for PAH/CTEPH therapies

European criteria for CTEPH (additional) — PCWP ≤ 15 mm Hg and PVR > 2 Wood units

European additional CTEPH criteriaPulmonary capillary wedge pressure ≤ 15 mm Hg and pulmonary vascular resistance (PVR) > 2 Wood units (per European guidelines)

Mean PAP noteCTEPH is characterized by mean pulmonary artery pressure > 25 mm Hg in addition to the European criteria

Surgical contextIn patients with poor hemodynamics eligible for pulmonary endarterectomy, pretreatment with IV epoprostenol may be recommended

Prior Authorization

Document PAH diagnosis and combination criteria for PAH agents

When requesting authorization for any PAH agent, providers must demonstrate the diagnosis of PAH (WHO Group 1) and, if combination therapy is requested, that the combination meets policy criteria (different therapeutic classes and prior inadequate response when specified).

Prior Authorization

Prior authorization requirement for advanced PAH therapies

Prior authorization is required for advanced PAH therapies and for combination use; requests must document WHO Group 1 PAH and, for combination therapy, prior inadequate response to single‑agent therapy and class difference between agents.

Prior Authorization

PAH coverage — prior authorization and combo evidence

Authorization for listed PAH therapies requires documentation of a PAH (WHO Group 1) diagnosis; for combination therapy, submit evidence of failure/inadequate response to a single medication and that medications are from different therapeutic classes.

Prior Authorization

Prior authorization for advanced PAH therapies — combination documentation

Prior authorization is required for advanced PAH therapies; combination therapy requests must document prior inadequate response to a single medication and that the agents are from different therapeutic classes.

Prior Authorization

Prior authorization — listed PAH medications

Prior authorization is required for the listed PAH medications; for combination requests include documentation of WHO Group 1 PAH, failure of a single agent when specified, and that agents are from different therapeutic classes.

Prior Authorization

Prior authorization — combination prerequisites required

Prior authorization must accompany requests for the advanced PAH therapies listed; combination therapy requests must document failed response to single‑agent therapy and that combined agents belong to different therapeutic classes.

Prior Authorization

Prior authorization — WHO Group 1 and combo requirements

Prior authorization is required demonstrating WHO Group 1 PAH diagnosis and, if combination therapy is requested, prior inadequate response to a single medication plus use of medications from different therapeutic classes.

Prior Authorization

Prior authorization for combination therapy — confirm failed monotherapy

Prior authorization for combination therapy requires confirmation of a PAH (WHO Group 1) diagnosis and documentation that the patient had an inadequate response to a single medication before escalation to combination therapy.

Prior Authorization

Authorization length and re-authorization documentation

Initial and re‑authorizations for listed PAH drugs may be approved for up to 12 months; re‑authorization requires chart documentation demonstrating continued positive clinical response to therapy.

Prior Authorization

Benefit-specific prior authorization — medical vs pharmacy

Benefit assignment affects prior authorization processing — some parenteral/infusion therapies (e.g., Flolan, Remodulin, Veletri) are managed under the medical benefit while many oral agents are managed under the pharmacy benefit; prior authorization follows the assigned benefit.

Prior Authorization

Benefit-specific prior authorization for parenteral/infusion therapies

Parenteral and infusion therapies are often administered under the medical benefit and may require medical‑benefit prior authorization and supporting clinical documentation consistent with infusion/home‑infusion processes.

Prior Authorization

Prior authorization for infused prostanoids — document initiation and pump plan

Parenteral prostanoid therapies (continuous IV/subcutaneous infusion) require prior authorization with documentation of the multi‑step initiation process (inpatient dose‑ranging if applicable), central venous access, infusion pump plan, and ongoing maintenance/backup strategy.

Document inpatient initial dose‑ranging if performed
Document central venous catheter insertion and pump plan
Provide plan for pump maintenance and backup pump/access

Step Therapy

Combination therapy step requirement — document failed monotherapy

When used as combination therapy, the policy requires that the individual has failed to demonstrate an adequate response to a single medication and that combined medications are from different therapeutic classes; include this in the prior authorization submission.

Step Therapy

Step therapy for combination regimens — failure of single agent required

For combination regimens, step‑therapy logic requires evidence the patient failed to demonstrate an adequate response to a single medication before adding another class; explicit trial durations are not specified in the policy excerpt.

Step Therapy

Step therapy requirement — document inadequate response to single agent

Providers must document clinical evidence of failure or inadequate response to a single medication before coverage of additional agent(s) in combination therapy will be approved.

Step Therapy

Step therapy — require failure of single agent and different classes for combination

Before adding agents from other classes, provide documentation that the patient failed to demonstrate an adequate response to a single medication; combinations of agents from the same class are not supported.

Confirm prior trial of single agent from a different therapeutic class than the proposed add‑on
Avoid combinations of medications from the same therapeutic class

Step Therapy

Step/sequence requirement before combination therapy

Combination therapy is covered only after documented failure to demonstrate adequate response to a single medication; the single medication must be from a different therapeutic class than the proposed add‑on.

Step Therapy

Step-therapy for combination use — failed single agent required

For combination therapy requests, include documentation that the patient failed to demonstrate an adequate response to a single medication before approval of combination regimens will be considered.

Step Therapy

Step requirement before combination therapy — submit evidence of failure

Individuals must have failed to demonstrate an adequate response to a single medication prior to escalation to combination therapy; include clinical notes showing the inadequate response.

Step Therapy

Step requirement — prior failed monotherapy required

Combination therapy is authorized only after failure to demonstrate adequate response to a single medication; ensure prior therapy and response are clearly documented in the request.

Step Therapy

Step therapy for combination regimens — document prior inadequate response

Step criteria for combination therapy require documented failure to an adequate response to a single medication prior to coverage of combination regimens; include medication history and response.

Step Therapy

Step therapy — prior failure required before adding agents

Prior to adding additional agents in combination, submit documentation showing prior failure to a single medication; the policy requires prior inadequate response before approving combination use.

Step Therapy

Step requirement — document inadequate response before combination

The policy indicates a step requirement: failure or inadequate response to a single medication is required before approving combination therapy; provide clinical evidence in chart notes.

Step Therapy

Step and brand-specific requirements — trial of generic before brand

Many brand products require prior trial and inadequate response or intolerance to generic versions (e.g., ambrisentan, macitentan, treprostinil); combination therapy also requires prior failure to single‑agent therapy and agents from different classes.

Document prior trial and inadequate response/intolerance to generic where brand step is specified
When combining agents, document failed response to single‑agent therapy from a different class

Note

Step therapy — no additional explicit rules in benefit table

No additional explicit step‑therapy rules beyond those stated are present in the referenced chunks.

Documentation Required

Document conventional/background therapy when applicable

The policy endorses use of conventional therapies (e.g., diuretics, oxygen, anticoagulation where appropriate) as part of management; document concurrent conventional therapy as clinically indicated when requesting advanced agents.

Document use of diuretics, oxygen, and anticoagulation when clinically indicated

Step Therapy

Consider background therapy for oral treprostinil

Consider background therapy when using oral treprostinil — trial evidence shows modest short‑term benefit and many RCTs enrolled treatment‑naïve or background‑treated individuals; include prior PAH therapy history in the request.

Include prior use of PDE5 inhibitors, endothelin receptor antagonists, or prostanoids when relevant

Documentation Required

Provide clinical documentation supporting PAH diagnosis and therapy choice

Providers should supply documentation supporting the diagnosis of PAH (WHO Group 1) and the clinical rationale for selecting the specified agent(s); the policy is intended for providers and the criteria set coverage requirements.

Documentation Required

Required clinical documentation — PAH diagnosis and combo evidence

Required clinical documentation must include a diagnosis of PAH, WHO Group 1; for combination therapy include documentation showing prior inadequate response to a single medication and that the combined agents are from different therapeutic classes.

Diagnosis specifying WHO Group 1
Medication history showing prior trial and response
Evidence that combined agents are from different therapeutic classes

Documentation Required

Required documentation — failed response and class difference for combos

Documentation must show diagnosis of PAH (WHO Group 1) and, when combination therapy is requested, evidence the patient failed to demonstrate an adequate response to a single medication and that concomitant medications are from different therapeutic classes.

Documentation Required

Documentation — support PAH diagnosis, agent class, and prior response

Documentation supporting requests must include PAH (WHO Group 1) diagnosis and, for combination therapy, either that medications are from different therapeutic classes and that the patient had an inadequate response to a single medication when required by the criteria.

Documentation Required

Documentation — PAH diagnosis and combination prerequisites

Documentation submitted must support the diagnosis of PAH (WHO Group 1) and, for combination therapy, include evidence of inadequate response to a single medication and that the medications are from different therapeutic classes.

Documentation Required

Documentation — confirm WHO Group 1 and failed monotherapy for combos

Documentation must demonstrate the diagnosis of PAH (WHO Group 1) and, for combination therapy, evidence of inadequate response to a single medication plus that medications are from different therapeutic classes.

Documentation Required

Documentation for combination therapy — show failed response to single agent

When requesting combination therapy, documentation must show diagnosis of PAH (WHO Group 1) and clinical evidence that the patient failed to demonstrate an adequate response to a single medication.

Documentation Required

Required clinical documentation — medication trials and responses

Clinical documentation must support PAH (WHO Group 1) diagnosis and show that the patient failed to demonstrate an adequate response to a single medication when combination therapy is requested; include medication trial details.

Documentation Required

Required clinical documentation — PAH diagnosis and combo evidence

Documentation must support PAH (WHO Group 1) diagnosis and, for combination therapy, evidence of inadequate response to a single medication and that agents are from different therapeutic classes.

Documentation Required

Required clinical documentation — failed response and class verification

Required clinical documentation includes proof of PAH (WHO Group 1) diagnosis and, for combination therapy, documentation that the patient failed to demonstrate an adequate response to a single medication and that medications are from different classes.

Documentation Required

Submit office visit notes and medication history

Submit medical records documenting medical necessity including office visit notes with diagnosis, relevant history, physical evaluation, and medication history when requesting authorization.

Billing Rule

Use specified billing codes from Coding section

Use the HCPCS/J-codes and other billing codes listed in the Coding section when submitting claims (examples include J1325, J3285, J3490, J3590, J7686, K0455, Q4074).

Documentation Required

Document agent and route to match benefit assignment

Ensure the medical record or claim indicates the specific agent and route of administration so benefit assignment aligns with the plan (e.g., IV infusions like Flolan/Remodulin under the medical benefit; oral riociguat under pharmacy benefit).

Documentation Required

Prostanoid administration documentation — initiation, catheter, pump

For prostanoid administration (e.g., epoprostenol), include documentation of inpatient initial dose‑ranging (if performed), central venous catheter insertion and pump training, and availability of backup pump/access to reduce risk of rebound pulmonary hypertension.

Record inpatient dose‑ranging details if done
Document central venous catheter placement and portable pump plan
Document backup pump/access availability and maintenance plan

Denial Risk

Diagnosis requirement — coverage limited to PAH (WHO Group 1)

Coverage is limited to individuals with a diagnosis of pulmonary arterial hypertension (PAH, WHO Group 1); requests for other WHO groups or non‑PAH indications risk denial.

Denial Risk

Denial risk — missing diagnosis or combo documentation

Requests that do not document a diagnosis of PAH (WHO Group 1) or, for combination therapy, failure to demonstrate an adequate response to a single medication and that agents are from different therapeutic classes may be denied.

Denial Risk

Denial triggers — lack of WHO Group 1 diagnosis or failed monotherapy

Requests may be denied if the individual does not have a diagnosis of PAH (WHO Group 1) or, when combination therapy is requested, has not failed to demonstrate an adequate response to a single medication from a different therapeutic class.

Denial Risk

Denial triggers for combination therapy — missing class or failure evidence

Combination therapy requests lacking documentation that medications are from different therapeutic classes or lacking documentation of inadequate response to a single medication may be denied.

Denial Risk

Denial triggers — unmet diagnosis or combination criteria

Requests that do not document WHO Group 1 PAH or do not meet the combination‑therapy criteria (failed response to single medication and agents from different therapeutic classes) risk denial.

Denial Risk

Potential denial triggers — criteria not met

Coverage is for PAH (WHO Group 1); requests failing to meet required criteria (e.g., incorrect diagnosis group or missing combination‑therapy prerequisites) may trigger denial.

Denial Risk

Denial triggers for combination therapy — failed monotherapy required

Requests for combination therapy may be denied if the individual does not have a diagnosis of PAH (WHO Group 1) or has not failed to demonstrate an adequate response to a single medication from a different therapeutic class.

Denial Risk

Combination therapy prerequisites — risk of denial if unmet

Requests for combination therapy may be denied if the individual lacks a PAH (WHO Group 1) diagnosis or has not failed to demonstrate an adequate response to a single medication from a different therapeutic class.

Denial Risk

Denial triggers for therapy requests — missing diagnosis or combo evidence

Requests for listed PAH agents may be denied when the individual does not have a PAH (WHO Group 1) diagnosis, or when combination therapy lacks documentation of prior inadequate response to single‑agent therapy and/or contains agents from the same therapeutic class.

Denial Risk

Denial triggers — ensure diagnostic and combo requirements met

Requests may be denied if the individual does not have PAH (WHO Group 1) or does not meet combination therapy requirements; include diagnostic and trial documentation to avoid denial.

Denial Risk

Combination therapy prerequisites — document failed response and class difference

When used as combination therapy, coverage requires that the individual has failed to demonstrate an adequate response to a single medication and that medications are from different therapeutic classes; lack of documentation of these conditions could trigger denial.

Denial Risk

Investigational use exclusions — non‑PAH PH (WHO Groups 2–5)

Use of listed medications for non‑PAH pulmonary hypertension (WHO Groups 2–5) is considered investigational and may be denied; ensure indication matches WHO Group 1 (or Group 4 for riociguat where indicated).

Denial Risk

Benefit assignment impacts coverage and processing

Benefit assignment (medical vs pharmacy) may affect coverage processing; therapies billed to the wrong benefit (e.g., medical‑managed infusion billed to pharmacy) may be denied or denied for incorrect benefit assignment.

Denial Risk

Benefit application mismatch — verify medical vs pharmacy benefit

Requests may be denied if benefit application is inconsistent with the plan's designation of specific agents under medical versus pharmacy benefit; verify benefit assignment prior to billing/submission.

Denial Risk

Riociguat — do not combine with PDE5 inhibitors (contraindicated)

Concurrent use of riociguat with a phosphodiesterase‑5 inhibitor (sildenafil, tadalafil, or vardenafil) is contraindicated; such combinations should not be requested and may be denied.

Do not combine riociguat with PDE5 inhibitors (sildenafil, tadalafil, vardenafil)

The policy’s combination therapy rule requires documented failure or inadequate response to monotherapy prior to coverage of add‑on therapy. When combination therapy is requested, the request must show the patient has failed to demonstrate an adequate response to a single medication before escalation to a regimen that includes additional classes.

The policy repeatedly emphasizes that the covered population is patients with PAH (WHO Group 1); coverage entries across multiple agent sections restate this requirement to ensure correct application.

The combination therapy requirement is restated throughout the criteria: to be covered, combination regimens must show prior inadequate response to monotherapy and include agents from different therapeutic classes; this rule is applied across listed agents and formulations.

PAH diagnosis typically requires right heart catheterization to measure pulmonary hemodynamics; the policy references hemodynamic thresholds (e.g., mean pulmonary artery pressure) used to define pulmonary hypertension and to support agent‑specific criteria where applicable.

The policy defines ‘failed to demonstrate an adequate response’ as a clinical determination that the individual did not achieve an adequate therapeutic response to a single medication; documentation of this inadequate response is required before combination therapy is authorized.

Multiple sections consistently require the PAH (WHO Group 1) diagnosis for coverage and reiterate the combination‑therapy preconditions, underscoring that these are core elements of the policy’s applicability.

The policy’s definition of the population—PAH, WHO Group 1—is restated in several locations to emphasize that the listed agents and coverage conditions apply within this specific diagnostic group.

Operationally, an ‘inadequate response’ is the clinical finding that, despite therapy, the patient has not achieved the expected therapeutic benefit and therefore requires consideration for combination therapy; the policy requires documentation of this finding prior to approving combination regimens.

Right heart catheterization hemodynamic criteria are referenced in the policy and are necessary to define the presence and severity of pulmonary hypertension in some agent‑specific criteria (for example, Yutrepia requires PVR and PCWP thresholds from RHC).

Table 1 maps therapies and therapeutic classes to PAH (WHO Group 1) and indicates benefit assignment (medical vs pharmacy) for many agents; this supports clinical application of the coverage rules to specific products.

The policy notes that pulmonary hypertension is classified by WHO into five groups and that PAH corresponds to Group 1; correct WHO group classification is essential to determining whether a requested therapy falls within covered indications.

Therapeutic-class requirement

Medications used concurrently must be from different therapeutic classes for combination therapy to meet criteria.

DocumentationMedical records must show failed/inadequate response to single-agent therapy and that agents are from different classes when combination therapy is requested.

inv-133: PAH (WHO Group 1) — reiteration of required diagnostic group

ReiterationPAH (WHO Group 1) is the explicit diagnostic group required for coverage of listed therapies in this policy section.

Clinical applicationEach agent-specific coverage entry references PAH, WHO Group 1 as the indication for medical necessity determinations.

Provider requirementProviders must supply documentation supporting the PAH, WHO Group 1 diagnosis when requesting authorization.

inv-134: PAH, WHO Group 1 — requirement for coverage

Coverage requirementCoverage for listed PAH agents requires a documented diagnosis of PAH, WHO Group 1.

Combination exceptionWhen used in combination, additional conditions (failed single-agent response and different therapeutic classes) must be documented.

Policy scopeApplies across the listed oral, inhaled, and parenteral PAH therapies unless agent-specific criteria state otherwise.

inv-135: PAH, WHO Group 1 — additional mention

MentionPAH, WHO Group 1 is repeatedly specified as the required diagnosis for consideration of listed therapies and combination regimens.

ConsistencyThe requirement is consistent across multiple agent entries and coverage sections in the policy.

ImplicationRequests lacking PAH, WHO Group 1 documentation risk denial per the policy's denial triggers.

inv-136: Combination therapy coverage rule — restated definition

Definition restatedCombination therapy coverage requires that the patient has failed to demonstrate an adequate response to a single medication before adding another agent.

Different classesConcurrent agents must be from different therapeutic classes to qualify as a covered combination regimen.

Documentation neededMedical records must document the inadequate response and class-difference to support prior authorization requests.

inv-137: PAH, WHO Group 1 — noted in chunk set

Policy notePAH, WHO Group 1 is the indicated diagnosis for combination therapy consideration; coverage contingent on meeting combination preconditions.

Agent-level consistencyAgent-specific entries mirror the general requirement for PAH, WHO Group 1 and combination therapy conditions.

Provider actionEnsure documentation of WHO Group 1 diagnosis in authorization submissions for combination regimens.

inv-138: Combination therapy requirement — restated requirement

RequirementCombination therapy is allowed only after documented failure to demonstrate an adequate response to a single medication AND when agents are from different therapeutic classes.

Step logicPolicy applies a step requirement before approving combination regimens; explicit trial durations are not specified in the excerpt.

Denial riskLack of documentation for either condition may trigger denial under the policy's denial triggers.

inv-139: PAH, WHO Group 1 — defined

DefinitionPAH, WHO Group 1 — the population for which the listed therapies and combination regimens are medically necessary when criteria are met.

Coverage implicationTreatment for non-WHO Group 1 pulmonary hypertension (Groups 2-5) is not covered under these PAH criteria and may be investigational.

Provider guidanceConfirm WHO Group 1 classification when submitting authorization requests for PAH therapies.

inv-140: Failed to demonstrate an adequate response — defined operationally

Operational definition'Failed to demonstrate an adequate response' means there is documented clinical evidence that a single medication did not provide an adequate therapeutic response prior to initiating combination therapy.

Documentation examplesClinical notes indicating persistent or progressive symptoms, lack of objective improvement, or intolerance leading to discontinuation can support the determination (policy requires documentation but does not prescribe exact metrics in the excerpt).

RequirementThis documented failure is a prerequisite for approval of combination therapy under the policy.

inv-147: CTEPH — chronic thromboembolic pulmonary hypertension definition

DefinitionChronic thromboembolic pulmonary hypertension (CTEPH) — pulmonary hypertension due to organized thrombi obstructing pulmonary vasculature; diagnosed by V/Q scan and pulmonary angiography.

Clinical contextCTEPH may follow acute pulmonary embolism and is characterized by progressive vascular remodeling leading to right heart failure.

Policy implicationAdempas (riociguat) is addressed under CTEPH-specific criteria within the policy (WHO Group 4 entries).

inv-148: Hemodynamic criteria for Yutrepia — PVR >= 5 Wood units and PCWP <= 15 mmHg

Agent-specific hemodynamicsFor Yutrepia (treprostinil inhalation powder), required hemodynamics are: PVR >= 5 Wood units AND PCWP <= 15 mmHg from right heart catheterization.

Associated clinical criteriaAlso requires WHO functional class II–IV symptoms and prior inadequate response to an ERA and a PDE5 inhibitor or an sGC stimulator.

Quantity limit noteYutrepia quantity is limited to 140 capsules per 28 days as specified in the policy.

inv-150: Pulmonary hypertension (PH) — diagnostic mean PAP >= 25 mm Hg

Diagnostic definitionPulmonary hypertension (PH) is increased arterial pressure in the lung vasculature; definitive diagnosis is usually by right heart catheterization with mean pulmonary arterial pressure of at least 25 mmHg.

ClassificationThe WHO classifies PH into five groups; PAH corresponds to WHO Group 1.

Clinical relevancemPAP ≥ 25 mmHg is the hemodynamic threshold used to confirm PH and direct further evaluation and management.

inv-152: CTEPH — diagnostic characterization by V/Q scan and hemodynamics

CTEPH hemodynamic characterizationEuropean criteria for CTEPH include PCWP ≤ 15 mm Hg and PVR > 2 Wood units; diagnosis is aided by V/Q scan and pulmonary angiography.

Policy cross-referenceYutrepia and riociguat entries reference hemodynamic criteria when applicable to agent-specific coverage decisions.

OperabilitySurgical candidacy (pulmonary endarterectomy) remains mainstay for operable CTEPH; medical therapy reserved when surgery is not an option or residual disease persists.

inv-153: 6MWD — six-minute walk distance definition and typical values

DefinitionSix-minute walk distance (6MWD) — exercise capacity measure commonly used as a primary outcome in PAH trials; pooled mean improvements across drug classes are approximately 27–46 meters.

Evidence role6MWD improvements support short‑term efficacy findings in RCTs and meta‑analyses but are imperfect surrogates for long‑term clinical outcomes.

Provider note6MWD changes may be included in documentation but policy cautions reliance on 6MWD alone for long‑term clinical benefit determinations.

inv-154: Parenteral prostanoid initiation — three-step process described

ProcessParenteral prostanoid initiation typically involves: (1) inpatient initial dose‑ranging; (2) central venous catheter insertion with portable infusion pump and backup pump access; (3) ongoing pump/catheter maintenance and monitoring due to risks of rebound PH if infusion stops.

ComplicationsPotential complications include catheter thrombosis, sepsis, and pump malfunction; documentation of mitigation plans is required for authorization of infused therapies.

Authorization implicationPrior authorization for continuous IV/subcutaneous prostanoids requires documentation of the multi‑step initiation and maintenance plan per policy guidance.