| Coverage Policy Manual | |
| Policy #: | 1998144 |
| Category: | Pharmacy |
| Initiated: | August 1998 |
| Last Review: | September 2023 |
|
|
|
|||||||||||
| Pulmonary Arterial Hypertension, Infusion and Selected Inhalation therapy | |
|
|
|
| Description: |
Pulmonary arterial hypertension (PAH) is defined by the American College of Cardiology Foundation and the American Heart Association (McLaughlin on behalf of the ACCF/AHA, 2009) as a mean pulmonary artery pressure of 25 mm Hg or greater at rest, or 30 mm Hg or greater with exercise, and a pulmonary capillary wedge or left atrial pressure less than 15 mm Hg. PAH is a rare and debilitating disease associated with abnormal proliferation of smooth muscle cells in the pulmonary arterial system. Prolonged increase in pulmonary artery pressure is associated with increasing shortness of breath and failure of pumping mechanism of the right ventricle and early death.
Elevated pulmonary artery pressure may result from a wide variety of conditions that affect either the heart, the chest/lungs, the liver, or the blood. For some individuals, pulmonary hypertension may be ameliorated by correcting the basic pathological problem; however, for individuals with idiopathic pulmonary arterial hypertension or for pulmonary hypertension secondary to certain primary diseases of the heart or lungs, drugs have been developed which may reduce the pulmonary artery pressure without compromising the normal cardiac output.
In addition to older therapy with oxygen, anticoagulation, and calcium channel antagonists, newer specialty pharmacy drugs have been proven to be effective and approved by the FDA for treatment of various stages of pulmonary arterial hypertension. Advanced pharmacologic therapies for PAH are defined as newer specialty pharmacy drugs specifically intended to impact the natural history of PAH, rather than treat disease manifestations. PAH-specific agents include prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase inhibitors.
Pulmonary Hypertension Classification
The 2013 WHO classification of Pulmonary Hypertension (PH), which is based on the consensus of an international group of experts at the Sixth World Symposium on Pulmonary Hypertension, is the most widely used system used in clinical care and research (Simonneau et al, 2013 and 2019)
There are 5 WHO categories of PH based on the etiology of the pulmonary hypertension:
For each category, there are numerous subcategories indicating more specific disease etiologies. Individuals in the first group are considered to have pulmonary arterial hypertension (PAH). Individuals in the remaining four groups are considered to have PH.
The World Health Organization (WHO) and New York Heart Association (NYHA) further classify individuals with pulmonary hypertension based on functional ability:
WHO Group 1 (PAH) Medication Classification
The classes of medications with FDA approvals for treatment of PAH are as follows:
Regulatory Status
Regulatory status of infusion and inhalation advanced treatment medications for Pulmonary Arterial Hypertension are listed below. (Listed by Drug (Brand) Name, Manufacturer, FDA Approval Date, Route of Administration)
Coding
See CPT/HCPCS Code section below.
|
|
|
|
|
Policy/ Coverage: |
This policy only addresses PAH infusion and selected inhalation therapy.
Oral agents (e.g., ambrisentan, bosentan, macitentan, riociguat selexipag sildenafil, tadalafil, treprostinil) and treprostinil inhalation are not allowed on the medical benefit, please refer to the applicable pharmacy benefit plan(s).
Effective April 01, 2022 Prior Approval is required for sildenafil.
The Step Therapy Medication Act is applicable to fully-insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart, Tyson or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
This policy addresses the use of PAH infusion and selected inhalation therapy in the outpatient setting only for chronic treatment of PAH. This policy does not apply to the use of PAH infusion and selected inhalation therapy in the inpatient or emergency room settings.
Effective September 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
PULMONARY ARTERIAL HYPERTENSION (PAH)
Combination therapy for the treatment of PAH (*World Health Organization [WHO] Group I) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL of the following conditions are met (see Policy Guidelines section):
Combination therapy with tadalafil and ambrisentan as first-line treatment meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the treatment of treatment naïve individuals with PAH who have *WHO Functional Class Groups II and III disease.
Dosage and Administration
Dosing per FDA Guidelines
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Combination therapy with macitentan, tadalafil, and selexipag, for any indiciation or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, combination therapy with macitentan, tadalafil, and selexipag, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The use of other advanced therapies for the pharmacologic treatment of PAH (*WHO group 1) that are not approved by the U.S. Food and Drug Administration for this indication, including but not limited to imatinib, simvastatin, and atorvastatin, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the use of other advanced therapies for the pharmacologic treatment of PAH (*WHO group 1) that are not approved by the U.S. Food and Drug Administration for this indication, including but not limited to imatinib, simvastatin, and atorvastatin, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
PULMONARY HYPERTENSION (PH)
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, sildenafil, tadalafil, or vardenafil does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of pulmonary hypertension (PH; *WHO Groups 2-5), including but not limited to:
For members with contracts without primary coverage criteria, the use of epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, sildenafil, tadalafil, or vardenafil is considered investigational for the treatment of pulmonary hypertension (PH; *WHO Groups 2-5), including but not limited to:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Riociguat (e.g., Adempas) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH; *WHO group 4) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the following conditions:
Dosage and Administration
Dosing per FDA Guidelines
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Riociguat or medications specific to PAH to reduce pulmonary vascular resistance before surgery in individuals with CTEPH who are considered candidates for pulmonary endarterectomy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, riociguat or medications specific to PAH to reduce pulmonary vascular resistance before surgery in individuals with CTEPH who are considered candidates for pulmonary endarterectomy is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Riociguat does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of PH (*WHO groups 2, 3, and 5), for any indication or circumstance not described above.
For members with contracts without primary coverage criteria, riociguat, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
* Pulmonary Hypertension Classification (2019 WHO classification of PH)
POLICY GUIDELINES
Treatment with epoprostenol requires 3 steps: initial dose-ranging, catheter insertion and portable pump attachment, and catheter and pump maintenance.
Treatment with iloprost requires the use of a specialized dispensing device.
Oral treprostinil should only be prescribed by a physician with expertise in treating pulmonary arterial hypertension, including administration of infused prostanoids.
For combination treatment, riociguat should not be combined with a phosphodiesterase type 5 inhibitor (sildenafil, tadalafil, vardenafil).
Effective November 16, 2022 to August 2023
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Pulmonary Arterial Hypertension (PAH)
Combination therapy for the treatment of PAH (*World Health Organization [WHO] Group I) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL of the following conditions are met (see Policy Guidelines section):
Combination therapy with tadalafil and ambrisentan as first-line treatment meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the treatment of treatment naïve individuals with PAH who have *WHO Functional Class Groups II and III disease.
Dosage and Administration
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Combination therapy with macitentan, tadalafil, and selexipag as first-line treatment does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the treatment of treatment naïve individuals with PAH.
For members with contracts without primary coverage criteria, combination therapy with macitentan, tadalafil, and selexipag as first-line treatment is considered investigational in the treatment of treatment naïve individuals with PAH.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The use of other advanced therapies for the pharmacologic treatment of PAH (*WHO group 1) that are not approved by the U.S. Food and Drug Administration for this indication, including but not limited to imatinib, simvastatin, and atorvastatin, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the use of other advanced therapies for the pharmacologic treatment of PAH (*WHO group 1) that are not approved by the U.S. Food and Drug Administration for this indication, including but not limited to imatinib, simvastatin, and atorvastatin, is considered investigational.
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Pulmonary Hypertension (PH)
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, sildenafil, tadalafil, or vardenafil does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for the treatment of pulmonary hypertension (PH; *WHO Groups 2-5), including but not limited to:
For members with contracts without primary coverage criteria, the use of epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, sildenafil, tadalafil, or vardenafil is considered investigational for the treatment of pulmonary hypertension (PH; *WHO Groups 2-5), including but not limited to:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Chronic Thromboembolic Pulmonary Hypertension
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
The use of riociguat (e.g., Adempas) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH; *WHO group 4) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the following conditions:
Dosage and Administration
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
The use of riociguat or medications specific to PAH to reduce pulmonary vascular resistance before surgery in individuals with CTEPH who are considered candidates for pulmonary endarterectomy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the use of riociguat or medications specific to PAH to reduce pulmonary vascular resistance before surgery in individuals with CTEPH who are considered candidates for pulmonary endarterectomy is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
The use of riociguat does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of PH (*WHO groups 2, 3, and 5), including but not limited to:
For members with contracts without primary coverage criteria, the use of riociguat is considered investigational for the treatment of PH (*WHO groups 2, 3, and 5), including but not limited to:
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
* Pulmonary Hypertension Classification (2019 WHO classification of PH)
POLICY GUIDELINES
Treatment with epoprostenol requires 3 steps: initial dose-ranging, catheter insertion and portable pump attachment, and catheter and pump maintenance.
Treatment with iloprost requires the use of a specialized dispensing device.
Oral treprostinil should only be prescribed by a physician with expertise in treating pulmonary arterial hypertension, including administration of infused prostanoids.
For combination treatment, riociguat should not be combined with a phosphodiesterase type 5 inhibitor (sildenafil, tadalafil, vardenafil).
Effective April 1, 2022 to November 15, 2022
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
EPOPROSTENOL (e.g., Flolan® injection, Veletri® injection)-prostacyclin analogue
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
EPOPROSTENOL injection meets primary coverage criteria for effectiveness and is covered for the treatment of PAH (World Health Organization [WHO Group I]) for:
WHO Functional Class III and IV individuals:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
EPOPROSTENOL injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, EPOPROSTENOL injection is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
ILOPROST (e.g., Ventavis® inhalation)-prostacyclin analogue
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
ILOPROST inhalation meets primary coverage criteria for effectiveness and is covered for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
WHO Functional Class III and IV individuals:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
ILOPROST inhalation does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, ILOPROST is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
SELEXIPAG (e.g., Uptravi® injection)-prostacyclin receptor agonist
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
SELEXIPAG injection meets primary coverage criteria for effectiveness and is covered for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
WHO Functional Class III and IV individuals who meet criteria for oral selexipag but are temporarily unable to take oral selexipag:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
SELEXIPAG injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, SELEXIPAG is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
SILDENAFIL (e.g., Revatio® injection)-phosphodiesterase-5 (PDE-5I) inhibitor
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
SILDENAFIL injection meets primary coverage criteria for effectiveness and is covered in adults for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
INITIAL APPROVAL for up to 12 months:
WHO Functional Class III and IV individuals unable to take oral sildenafil or in whom oral sildenafil is inadequate:
CONTINUATION OF THERAPY for 12 months:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
SILDENAFIL injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, SILDENAFIL is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
TREPROSTINIL (e.g., Remodulin® injection)-prostacyclin analogue
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
TREPROSTINIL (Remodulin® injection) meets primary coverage criteria for effectiveness and is covered for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
TREPROSTINIL injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, TREPROSTINIL is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Dosage and administration:
Please refer to a separate policy on Site of Care or Site of Service Review (policy # 2018030) for pharmacologic/biologic medications.
EFFECTIVE JANUARY 01, 2022 to March 31, 2022
This policy only addresses PAH infusion and selected inhalation therapy.
Oral agents (e.g., ambrisentan, bosentan, macitentan, riociguat selexipag sildenafil, tadalafil, treprostinil) and treprostinil inhalation are not allowed on the medical benefit, please refer to the applicable pharmacy benefit plan(s).
EPOPROSTENOL (e.g., Flolan® injection, Veletri® injection)-prostacyclin analogue
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
EPOPROSTENOL injection meets primary coverage criteria for effectiveness and is covered for the treatment of PAH (World Health Organization [WHO Group I]) for:
WHO Functional Class III and IV individuals:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
EPOPROSTENOL injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, EPOPROSTENOL injection is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
ILOPROST (e.g., Ventavis® inhalation)-prostacyclin analogue
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
ILOPROST inhalation meets primary coverage criteria for effectiveness and is covered for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
WHO Functional Class III and IV individuals:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
ILOPROST inhalation does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, ILOPROST is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
SELEXIPAG (e.g., Uptravi® injection)-prostacyclin receptor agonist
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
SELEXIPAG injection meets primary coverage criteria for effectiveness and is covered for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
WHO Functional Class III and IV individuals who meet criteria for oral selexipag but are temporarily unable to take oral selexipag:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
SELEXIPAG injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, SELEXIPAG is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
SILDENAFIL (e.g., Revatio® injection)-phosphodiesterase-5 (PDE-5I) inhibitor
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
SILDENAFIL injection meets primary coverage criteria for effectiveness and is covered in adults for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
WHO Functional Class III and IV individuals unable to take oral sildenafil or in whom oral sildenafil is inadequate:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
SILDENAFIL injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, SILDENAFIL is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
TREPROSTINIL (e.g., Remodulin® injection)-prostacyclin analogue
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
TREPROSTINIL (Remodulin® injection) meets primary coverage criteria for effectiveness and is covered for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) for:
2. Individuals who require transition from epoprostenol to reduce the rate of clinical deterioration (FDA, 2020).
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
TREPROSTINIL injection does not meet member benefit certificate primary coverage criteria for any other circumstance that is not listed as covered above including but not limited to:
For members with contracts without primary coverage criteria, TREPROSTINIL is considered investigational for any other circumstance that is not listed as covered above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Dosage and administration:
Please refer to a separate policy on Site of Care or Site of Service Review (policy # 2018030) for pharmacologic/biologic medications.
Effective December 2019 - December 2021
The following drugs meet primary coverage criteria for effectiveness and are covered for selected conditions listed as Category I causes of pulmonary hypertension (see “Rationale” section for the classification of pulmonary hypertension).
The category I conditions that are covered are:
The category I conditions that are not covered include:
These drugs are not covered for Category II, III, IV, or V conditions as some of the conditions have been studied and the drugs found not to be effective (e.g., left ventricular failure; chronic thromboembolic pulmonary hypertension); some of these conditions are presently being studied in clinical trials to determine effectiveness (e.g., interstitial fibrotic lung disease); some of these conditions are corrected or treated by other means (e.g., sleep disordered breathing, alveolar hypoventilation disorders, developmental disorders); and for some of these conditions there is no evidence of effectiveness or safety available.
AMBRISENTAN (Letaris) is administered orally, and meets primary coverage criteria for effectiveness and is covered (Effective, June 2007) for treatment of patients with WHO/NYHA functional class II or III patients with Idiopathic pulmonary hypertension, idiopathic familial pulmonary hypertension, pulmonary hypertension associated with connective tissue disease, anorexigen use, or HIV infection.
AMBRISENTAN is not covered in combination with other endothelin antagonists, phosphodiesterase antagonists, prostacyclin, or prostacyclin analogue drugs as the safety and effectiveness of this use has not been established in appropriate trials.
AMBRISENTAN is not covered in combination with sildenafil, as this combination is being studied in a randomized, double blind, placebo controlled trial to determine the safety and effectiveness of this combination. (Effective, October 2011)
BOSENTAN (Tracleer) is administered orally, and is covered (Effective, Nov 2001) for patients with pulmonary artery hypertension with NYHA class III-IV symptoms with idiopathic pulmonary hypertension, familial pulmonary hypertension, anorexigenic agent induced pulmonary hypertension, pulmonary hypertension associated with scleroderma or its variants, in patients with Eisenmenger Syndrome, and in PAH associated with AIDS. Bosentan must be obtained through the manufacturer.
BOSENTAN is covered for patients with WHO/NYHA class II functional symptoms (Effective, Oct 2008).
BOSENTAN is not covered for the treatment of congestive heart failure with left ventricular dysfunction.
BOSENTAN is not covered in conjunction with epoprostenol, treprostinil, or phosphodiesterase inhibitors (e.g., sildenafil) as these combinations are presently being studied in trials to determine safety and effectiveness.
BOSENTAN is not covered for patients with NYHA class I functional symptoms as this use of bosentan is not FDA approved and has not been studied to determine effectiveness.
BOSENTAN is not covered to treat pulmonary hypertension in patients with pulmonary fibrosis as this use of bosentan is under study in clinical trials to determine safety and effectiveness.
BOSENTAN is not covered to treat pulmonary hypertension in patients with chronic thromboembolic disease as this use has been found in a randomized controlled clinical trial to be ineffective.
EPOPROSTENOL (Flolan, Veletri)
Epoprostenol is covered for patients with idiopathic pulmonary arterial hypertension who are NYHA class III or IV (Effective, Sep 1995); and for patients with pulmonary arterial heart disease (PAH) and NYHA class III or IV symptoms secondary to (1) scleroderma or scleroderma variants (Effective, Apr 2000); (2) congenital heart disease with left to right shunts, left to right shunts that have reversed, and pulmonary hypertension that has developed following repair of left to right shunts; (Effective, Jun 1999); and (3) anorexigenic agents (Effective, Jun 2000). Epoprostenol is usually not the initial drug of choice for these covered indications unless the patient is NYHA functional class IV. Epoprostenol and the portable controlled infusion device used to administer the drug are available through restricted distribution programs and are not available through community pharmacies.
EPOPROSTENOL is covered (Effective, Jul 2003) for treatment of familial idiopathic pulmonary hypertension in patients who are WHO/NYHA functional class III or IV.
EPOPROSTENOL is covered for patients with pulmonary arterial hypertension associated with HIV disease (Effective, Sep 2003), in patients who are WHO/NYHA functional class III or IV, but there are concerns regarding the safety of long-term central venous catheter placement because of the potential for infectious complications, which are increased in patients with HIV disease (Barst, 2007).
EPOPROSTENOL is covered (Effective, Nov 2008) when used in combination with sildenafil in patients with pulmonary arterial hypertension idiopathic, associated anorexigen use, connective tissue disease, or corrected congenital heart disease) who are receiving long-term intravenous epoprostenol therapy.
EPOPROSTENOL is not covered for patients with NYHA functional class I or II symptoms, as this use is not FDA approved, has not been studied in appropriate trials, and is not recommended in position papers from national or international study groups on pulmonary hypertension.
EPOPROSTENOL is not covered for combination use with bosentan, iloprost, treprostinil, or ambrisentan (except when transitioning to these drugs) as there is lack of evidence of effectiveness.
ILOPROST (Ventavis) is administered by inhalation and is an FDA designated orphan drug and is covered (Effective, Dec 2004) to treat WHO group I pulmonary hypertension with WHO/NYHA class III or IV symptoms. Iloprost oral inhalation solution and the nebulizers used to administer the drug are available through a restricted distribution program and are not available through community pharmacies.
ILOPROST is covered as add-on therapy for patients receiving bosentan who have continued to be symptomatic (Effective, June 2007).
ILOPROST is not covered when used in conjunction with epoprostenol, treprostinil, ambrisentan, sildenafil or tadalafil (except when transitioning to these medications) as the safety and effectiveness of these combinations has not been demonstrated in appropriate clinical trials.
ILOPROST is not covered for patients with NYHA functional class I or II symptoms, as patients in these symptomatic classes have not been studied to determine effectiveness.
SILDENAFIL (Revatio, Viagra) is administered orally, and is FDA approved and covered for patients with WHO/NYHA functional class II or III disease, due to pulmonary arterial hypertension categories of disease mentioned above (Effective, June 2005).
SILDENAFIL is covered when used in combination with epoprostenol in patients with pulmonary arterial hypertension (idiopathic, associated anorexigen use or connective tissue disease, or corrected congenital heart disease) who are receiving long-term intravenous epoprostenol therapy (Effective, October, 2008).
SILDENAFIL is not covered in combination with endothelin antagonists or prostacyclin analogue drugs as the safety and effectiveness of this use has not been established in appropriate trials.
SILDENAFIL is not covered in combination with ambrisentan, as this combination is being studied in a randomized, double blind, placebo controlled trial to determine the safety and effectiveness of this combination. (Effective, October 2011)
SILDENAFIL is not covered for the treatment of PAH in children ages 1 through 17. This treatment is not recommended by the FDA to be used in this age group. (Effective, September 2012)
TADALAFIL (Adcirca, Cialis) is administered orally. Adcirca was FDA approved in 2009 for the treatment of PAH (WHO GroupI) to improve exercise ability. Tadalafil is covered (Effective June 2009) for patients who have symptomatic PAH due to categories of disease as mentioned above.
TADALAFIL and Ambrisentan combination therapy as first-line treatment is covered in the treatment of treatment naïve PAH patients with WHO Functional Class Groups II and III.
TADALAFIL is not covered in conjunction with other PDE inhibitors, endothelin antagonists, or other drugs for pulmonary hypertension because of lack of evidence for effectiveness of combination therapy.
TREPROSTINIL (Remodulin) is administered by chronic subcutaneous (Effective Nov 2001) or intravenous (Effective, Nov 2003) administration, and is covered in patients with pulmonary arterial hypertension with NYHA class III-IV symptoms due to 1) idiopathic pulmonary hypertension, 2) scleroderma and scleroderma variants, 3) congenital heart disease resulting in pulmonary hypertension, and 4) anorexigenic agents.
TREPROSTINIL is not covered in conjunction with other prostacyclin analogues, endothelin receptor antagonists, or sildenafil as this combination therapy is presently under study to determine effectiveness and safety.
TREPROSTINIL (Tyvaso) is administered by oral inhalation, and meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of patients with pulmonary arterial hypertension (WHO Group I) with NYHA Class III symptoms, to increase walk distance. (Effective June, 2010)
Treprostinil does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in for the treatment of patients with non-PAH PH conditions (WHO Groups 2-5). (Effective June, 2010)
For contracts without primary coverage criteria, treprostinil for the treatment of patients with non-PAH PH conditions (WHO Groups 2-5) is considered investigational. Investigational services are an exclusion in most member benefit certificates of coverage. (Effective June, 2010)
TREPROSTINIL (Orenitram), oral tablet formulation, for the treatment of patients with pulmonary arterial hypertension does not meet member benefit certificate primary coverage criteria. (Effective April 2015)
For members with contracts without primary coverage criteria, treatment with treprostinil (Orenitram), oral tablet formulation, is considered not medically necessary. Services that are considered not medically necessary are specific contract exclusions in most member benefit certificates of coverage. (Effective April 2015)
Dosage and administration:
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Due to the detail of the policy statement, the document containing the coverage statements for dates prior to December 2019 are not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com
|
|
|
|
| Rationale: |
Due to the detail of the rationale, the complete document is not online. If you would like a hardcopy print, please email: codespecificinquiry@arkbluecross.com
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2018. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Tyrosine Kinase Inhibitors No RCTs were identified that evaluated imatinib as monotherapy for patients with PAH. Safety of imatinib in patients with PAH was assessed by Frost et al in a long-term extension of an RCT of imatinib as add-on third-line therapy (Frost, 2015). A total of 144 patients entered the extension study (66 patients had been on imatinib for 24 weeks, 78 patients were switching to imatinib from placebo). One hundred thirty-five (94%) of 144 patients discontinued the extension study, and about one-third of the patients discontinued because of adverse events. When the study was terminated (due to high dropout rate), the mean exposure to imatinib was 931 days in the group who took imatinib in the original RCT, and 590 days in the ex-placebo group. Seventeen (12%) of the 144 patients died during the study or within 30 days of leaving it. Serious adverse events (other than death) occurred in 40 (60.6%) patients in the group originally taking imatinib, and 53 (67.9%) in the ex-placebo group. The Statins In 2016, Anand et al published a systematic review of placebo-controlled randomized trials evaluating statins for treating PAH (Anand, 2015). Reviewers identified 4 RCTs, of which two evaluated simvastatin, one assessed atorvastatin, and one evaluated rosuvastatin. The total sample size was 387; 1 study had 220 patients, and the others had fewer than 100 patients each. The primary outcomes of the review were mortality and change in 6-minute walk distance (6MWD) from baseline to follow-up. A pooled analysis of data from 3 trials did not find a significant benefit of stains on mortality (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.32 to 1.74; I2=0%). Similarly, a pooled analysis of 3 trials did not find a significant benefit of statins on the 6MWD(weighted mean difference [WMD], -9.27 meters; 95% CI, -27.7 to 9.2 meters; I2=1.7%).
The largest trial was published in 2012 by Zeng et al (Zeng, 2012). This was a 6-month, double-blind, placebo-controlled randomized trial of 220 Chinese patients with PAH (83%) or chronic thromboembolic pulmonary hypertension (CTEPH; 6%) in World Health Organization (WHO) functional class II or III. Patients received atorvastatin 10 mg orally daily or matching placebo in addition to supportive care (diuretics, digoxin, warfarin). After 6 months, the mean difference in 6MWD (atorvastatin – placebo) was 2.5 meters (95% CI, -33 to 38 meters). There was no statistically significant difference between treatment groups in the proportion of patients who improved or deteriorated in WHO functional class or in hemodynamic parameters (right atrial pressure, pulmonary artery pressure, cardiac index, pulmonary vascular resistance (PVR), or mixed venous oxygen saturation). There were 9 (8%) deaths in the atorvastatin group and 11 (10%) deaths in the placebo group (p=0.31).
The 2004 Bosentan Randomized trial of Endothelin Antagonist Therapy for PAH (BREATH-2) trial compared epoprostenol alone with the combination of epoprostenol plus bosentan (Humbert, 2004). The trial was multicenter, double-blind, and placebo-controlled. It included 33 patients with PAH who were scheduled to begin treatment with epoprostenol. After 2 days of epoprostenol therapy, patients were randomized to add bosentan (n=22) or placebo (n=11). The double-blind treatment duration was 16 weeks, and the primary efficacy outcome was change in total pulmonary resistance. Five (15%) of 33 patients did not complete the study. At 16 weeks, mean change in total pulmonary resistance did not differ significantly between groups (-36.3 dyns-1cm5 ± 4.3% in the combination treatment group vs -22.6 ± 4.3% in the epoprostenol plus placebo group, p=0.08). Secondary outcomes also did not differ significantly between groups. For example, the 6MWD increased a median of 68 meters in the combination treatment group and 74 meters in the epoprostenol plus placebo group. Moreover, the modified New York Heart Association functional class improved for 59% of patients in the combination treatment group and 5 patients in the epoprostenol plus placebo group (p=NS).
CTEPH MONOTHERAPY In 2017, data on secondary outcomes from CHEST-1 were published by Kim et al (Kim, 2017). Study findings generally favored the riociguat group. At week 16, compared with baseline, PVR significantly decreased in the riociguat group (-29%) compared with the placebo group (+3%). There were also significantly improved outcomes in the riociguat group vs placebo for other hemodynamic outcomes (eg, systemic vascular resistance, mean pulmonary artery pressure, diastolic pulmonary artery pressure, cardiac output, mixed venous oxygen saturation, mean arterial pressure, diastolic pressure gradient; p<0.001 for each).
2019 Update
A literature search conducted through April 2019 did not reveal any new information that would prompt a change in the coverage statement.
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2020. No new literature was identified that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through May 2021. No new literature was identified that would prompt a change in the coverage statement.
September 2021 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2021. The following is a summary of the key new literature to date.
In 2019, the American College of Chest Physicians (ACCP) updated their guidelines on pharmacologic therapy for PAH in adults (Klinger et al, 2019) and made the following recommendation:
Simonneau et al (2008) conducted a controlled trial that randomly assigned 267 patients with group 1 PAH who were receiving epoprostenol to have sildenafil or placebo added for 16 weeks. Most patients were WHO functional class III at the beginning of the trial. The addition of sildenafil compared with placebo improved hemodynamic parameters, exercise capacity and time to clinical worsening.
Humbert et al (2004) conducted a trial (BREATHE-2 trial) that randomly assigned 22 patients with group 1 PAH who were receiving epoprostenol to have either bosentan or placebo added for 16 weeks. The patients demonstrated improvement with Epoprostenol. The addition of bosentan improved the outcomes of hemodynamic parameters, exercise capacity, and functional class to a greater degree than the addition of placebo, although the difference was not statistically significant.
McLaughlin et al (2010) conducted a trial (TRIUMPH) in which 235 patients with group 1 PAH who were deteriorating despite bosentan or sildenafil therapy were randomly assigned to receive the addition of either inhaled treprostinil or placebo for 12 weeks. The treprostinil group had a significant improvement in 6MWD and quality of life. However, there were no differences in the time to clinical worsening, dyspnea, or WHO functional class.
Ghofrani et al (2002 and 2003) conducted studies that demonstrated that the addition of sildenafil to inhaled iloprost resulted in an improvement in exercise capacity, WHO functional class, and hemodynamics in patients with group 1 PAH.
The effect of combining bosentan with iloprost is less clear. Hoeper et al (2003) conducted an early observational study which suggested that the combination was both safe and effective when bosentan was added to pre-existing inhaled iloprost therapy. However, in the subsequent trial performed by Hoeper et al in 2006 in which 40 patients with Group I PAH were randomzed to receive either bosentan alone or bosentan plus iloprost for 12 weeks, no difference in the 6MWD was demonstrated. But the results of the trial may have been skewed by outliers in the combination therapy group.
2022 Update
In the event-driven GRIPHON randomized-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag.
Patients randomized to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3 days and 30 days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019.
Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7 months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomized to selexipag in GRIPHON. Kaplan-Meier survival estimates (95%CI) at 1, 3, 5 and 7 years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively.
These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen. (Galiè N, Gaine S, Channick R, et.al., 2022)
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2023. No new literature was identified that would prompt a change in the coverage statement.
|
|
|
|
| CPT/HCPCS: | |
|
|
|
| References: |
McCrory DC, Coeytaux RR, Schmit KM et al.(2013) Pulmonary Arterial Hypertension: Screening, Management, and Treatment. Rockville MD2013. Available online at: http://effectivehealthcare.ahrq.gov/ehc/products/370/1414/hypertension-pulmonary-arterial-report-130524.pdf. Last accessed August 2013. Almagro P, Julia J, et al.(2002) Pulmonary capillary hemangiomatosis associated with primary pulmonary hypertension: report of 2 new cases and review of 35 cases from the literature. Medicine, 2002; 81:417-24. Anand V, Garg S, Duval S, et al.(2016) A systematic review and meta-analysis of trials using statins in pulmonary arterial hypertension. Pulm Circ. Sep 2016;6(3):295-301. PMID 27683606 Aquilar RV, Farber HW.(2000) Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med, 2000; 162:1846-50. Badesch DB, Abman SH, et al.(2007) Medical therapy for pulmonary arterial hypertension: Updated ACCP evidence-based clinical practice guidelines. Chest, 2007; 131:1917-28. Badesch DB, Tapson VF, et al.(2000) Continuous intravenous epoprostenol for pulmonary hypertension due to the sclerotic spectrum disease. A randomized controlled trial. Ann Int Med, 2000; 132:424-34. Barst RJ, et al.(1994) Survival in Primary Pulmonary Hypertension with Long-Term Continuous Intravenous Prostacyclin. Ann Int Med, 1994; 6:409-415. Barst RJ, Rubin LJ, Long WA, et al.(1996) A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. NEJM, 1996; 334:296-301. Chen YF, Jowett S, Barton P, et al.(2009) Clinical and cost-effectiveness of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for pulmonary arterial hypertension within their licensed indications: a systematic review and economic evaluation. Health Technol Assess. Oct 2009;13(49):1-320. PMID 19863849 Donti A, Formigari R, et al.(2007) Pulmonary arterial hypertension in the pediatric age. J Cardiovasc Med, 2007; 8:72-7. Dweik RA.(2002) Pulmonary hypertension and the search for the selective pulmonary vasodilator. Commentary. Lancet, 2002; 360:886-7. Feldman J, Im Y, Gill K.(2015) Oral treprostinil diethanolamine for pulmonary arterial hypertension. Expert Rev Clin Pharmacol. Jan 2015;8(1):55-60. PMID 25409915 Feldman J, Im Y, Gill K.(2015) treprostinil diethanolamine for pulmonary arterial hypertension. Expert Rev Clin Pharmacol. Jan 2015;8(1):55-60. PMID 25409915 Frost AE, Barst RJ, Hoeper MM, et al.(2015) Long-term safety and efficacy of imatinib in pulmonary arterial hypertension. J Heart Lung Transplant. Nov 2015;34(11):1366-1375. PMID 26210752 Galie N, Brundage BH, Ghofrani HA, et al.(2009) Tadalafil therapy for pulmonary arterial hypertension (PHIRST study). Circulation epub May 26, 2009. Galie N, Corris PA, Frost A, et al.(2013) Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. Dec 24 2013;62(25 Suppl):D60-72. PMID 24355643 Galie N, Corris PA, Frost A, et al.(2013) Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. Dec 24 2013;62(25 Suppl):D60-72. PMID 24355643 Galie N, Corris PA, Frost A, et al.(2013) Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. Dec 24 2013;62(25 Suppl):D60-72. PMID 24355643 Galiè N, Gaine S, Channick R, Coghlan JG, Hoeper MM, Lang IM, McLaughlin VV, Lassen C, Rubin LJ, Hsu Schmitz SF, Sitbon O, Tapson VF, Chin KM.(2022) Long-Term Survival, Safety and Tolerability with Selexipag in Patients with Pulmonary Arterial Hypertension: Results from GRIPHON and its Open-Label Extension. Adv Ther. 2022 Jan;39(1):796-810. doi: 10.1007/s12325-021-01898-1. Epub 2021 Oct 30. PMID: 34727317; PMCID: PMC8799580. Galiè N, Ghofrani HA, Torbicki A, et al.(2006) Sildenafil citrate therapy for pulmonary arterial hypertension. NEJM 2006; 354:2400. Galie N, Humbert M, Vachiery JL, et al.(2015) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. Oct 2015;46(4):903-975. PMID 26318161 Galie N, Torbicki A, et al.(2004) Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J, 2004; 25:2243-78. Ghofrani HA, et al.(2002) Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 2002; 136:515-22. Ghofrani HA, et al.(2002) Sildenafil for the treatment of lung fibrosis and pulmonary hypertension: a randomized controlled trial. Lancet, 2002; 360:895-900. Ghofrani HA, Rose F, Schermuly RT, et al(2003) Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension J Am Coll Cardiol 2003; 42:158 Ghofrani HA, Rose F, Schermuly RT, et al.(2003) Oral sildenafil as long-term adjunct therapy to inhaled Iloprost in severe pulmonary artery hypertension. JACC, 2003; 42:158-64. Ghofrani HA, Wiedemann R, Rose F, et al(2002) Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension Ann Intern Med 2002; 136:515 Haworth SG.(2008) The management of pulmonary hypertension in children. Arch Dis Child, 2008: HTTP://adc.bmj.com. Hoeper MM, Bogaard HJ, Condliffe R, et al. (2013) Definitions and Diagnosis of Pulmonary Hypertension. J Am Coll Cardiol. 2013; 62(suppl 25):D42- D50. Available at: http://www.onlinejacc.org/content/62/25_Supplement/D42. Hoeper MM, Taha N, Bekjarova A, et al(2003) Bosentan treatment in patients with primary pulmonary hypertension receiving nonparenteral prostanoids Eur Respir J 2003; 22:330 Hopkins W. and Rubin LJ. (2021) Treatment of pulmonary arterial hypertension (group 1) in adults: Pulmonary hypertension-specific therapy. Aug 18, 2021. Available at: https://www.uptodate.com Humbert M, Barst RJ, Robbins IM, et al(2004) Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2 Eur Respir J 2004; 24:353 Humbert M, Barst RJ, Robbins IM, et al.(2004) Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2 Eur Respir J. Sep 2004;24(3):353-359. PMID 15358690 Ivy DD, Abman SH, Barst RJ, et al. (2013) Pediatric Pulmonary Hypertension. J Am Coll Cardiol. 2013; 62(suppl 25):D117- D126. Available from: http://www.onlinejacc.org/content/62/25_Supplement/D117. Ivy DD, Claussen L, et al.(2007) Transition of stable pediatric patients with pulmonary arterial hypertension from intravenous Epoprostenol to intravenous Treprostinil. Am J Cardiol, 2007; 99:696-8. Jais X, D'Armini AM, et al.(2008) Bosentan for treatment of inoperative chronic pulmonary hypertension: BENEFIT (Bosentan Effects in iNopErable Forms of chronic Thrombocytopenic pulmonary hypertension), a randomized placebo-controlled trial. J Am Coll Cardiol, 2008; 62:1227-34. Jaïs X, D'Armini AM, Jansa P, et al.(2008) BENEFiT (Bosentan Effects in iNopErable Forms of chronic Bosentan for Treatment of Inoperable Chronic Thromboembolic Pulmonary hypertension), a randomized, placebo-controlled trial. J Am Cardiol. 2008:52;2127-2134. Jing ZC, Parikh K, Pulido T, et al.(2013) Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. Feb 5 2013;127(5):624-633. PMID 23307827 Jing ZC, Parikh K, Pulido T, et al.(2013) Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. Feb 5 2013;127(5):624-633. PMID 23307827 Kanthapillai P, Lasserson TJ, Walters EH.(2004) Sildenafil for pulmonary hypertension. The Cochrane Database Systematic Reviews; Issue 4; CD003562; 2004. Kim NH, D'Armini AM, Grimminger F, et al.(2017) Haemodynamic effects of riociguat in inoperable/recurrent chronic thromboembolic pulmonary hypertension. Heart. Apr 2017;103(8):599-606. PMID 28011757 Klinger JR, Elliott CG, Levine DJ, et al(2019) Therapy for Pulmonary Arterial Hypertension in Adults: Update of the CHEST Guideline an Expert Panel Report CHEST. 2019; 155(3): 565-586 Krishnan U, Takatsuki S, Ivy DD et al.(2012) Effectiveness and safety of inhaled treprostinil for the treatment of pulmonary arterial hypertension in children. Am J Cardiol 2012; 110(11):1704-9. Liu C, Chen J, Gao Y et al.(2013) Endothelin receptor antagonists for pulmonary arterial hypertension. The Cochrane Database Sys Rev 2013; 2:CD004434. Liu C, Chen J.(2006) Endolthelin receptor antagonists for pulmonary arterial hypertension. Cochrane Database of Systematic Reviews, 2006; issue 3:art. No. CD004434. McLaughlin V, Channick RN, Ghofrani HA, et al.(2015) Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. Aug 2015;46(2):405-413. PMID 26113687 McLaughlin VV, Archer SL, Badesch DB, et al. (2009) ACCF/AHA 2009 expert consensus document on pulmonary hypertension. A report of the ACCF Task Force on Expert Consensus Documents and the AHA. J Am Coll Cardiol. 2009; 53:1573-1619. Available at: http://circ.ahajournals.org/content/119/16/2250.full.pdf+html. McLaughlin VV, Benza RL, Rubin LJ, et al(2010) Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial J Am Coll Cardiol 2010; 55:1915 McLaughlin VV, Benza RL, Rubin LJ, et al.(2010) Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol. 2010 May 4;55(18):1915-22. McLaughlin VV, Oudiz RJ, et al.(2006) Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med, 2006; 174:1257-63. McLaughlin VV.(2012) Has the 6-min walk distance run its course? Chest. Dec 2012;142(6):1363-1364. PMID 23208324 McLaughlin VV.(2012) Has the 6-min walk distance run its course? Chest. Dec 2012;142(6):1363-1364. PMID 23208324 Mistry PK, Sirrs S, et al.(2002) Pulmonary hypertension in Type I Gaucher;s disease: genetic and epigenetic determinants of phenotype and response to therapy. Molec Genet Metabol, 2002; 77:91-8. Montani D, Achouh L, et al.(2008) Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcomes of 24 cases confirmed by histology. Medicine, 2008; 87:220-33. National Pulmonary Hypertension Centres of the UK and Ireland.(2008) Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax, 2008; 63(suppl II):ii1-ii41. National Pulmonary Hypertension Service, Gibbs JS.(2008) Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax, 2008; 63 (suppl II):ii1-ii41. Nunes H, Humbert M, et al.(2003) Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med, 2003; 167:1433-39. Olschewski H, Simonneau GM, et al.(2002) Inhaled iloporst for severe pulmonary hypertension. NEJM, 2002; 347:322-9. Opitz CF, Wesel R, et al.(2005) Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. Eur Heart J, 2005; 26:1895-1902. Oudiz RJ, Brundage BH, Galie N et al.(2012) Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study. J Am Coll Cardiol 2012; 60(8):768-74. Oudiz RJ, Schilz RJ, et al.(2005) Treprostinil, a prostacyclin analogue, in pulomary arterial hypertension associated with connective tissue disease. Chest, 2005; 126:240-7. Packer M, McMurray J, et al.(2005) Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. J Card Fail, 2005; 11:21-2. Packer M.(2002) Effects of the endothelin receptor antagonist bosentan on the morbidity and mortality in patients with chronic hreart failure: results of the Enable 1 and 2 trial program. American College of Cardiology 51st Annual Scientific Session, Atlanta, GA, 2002. Paramothayan NS, Lasserson TJ, et al.(2005) Prostacyclin for pulmonary hypertension in adults. Cochrane Database of Systematic Reviews, 2005;CD002994. Rich S.(2007) The value of approved therapies for pulmonary arterial hypertension. Am Heart J, 2007; 153:889-90. Rosenzweig EB, Ivy DD, et al.(2005) Effects of long-term Bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol, 2005; 46:697-704. Rosenzweig EB, Kerstein D, Barst RJ.(1999) Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation, 1999;99:1858-65. Rubin LJ, Badesch DB, et al.(2002) Bosentan therapy for pulmonary arterial hypertension. NEJM, 2002; 346:896-903. Rubin LJ, Galie N, Grimminger F, et al.(2015) Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. Jan 22 2015. PMID 25614164 Rubin LJ, Galie N, Grimminger F, et al.(2015) Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. Jan 22 2015. PMID 25614164 Rubin LJ, Mendoza J, et al.(1990) Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Int Med, 1990; 112:485-91. Rubin LJ.(1993) ACCP Consensus Statement. Chest 1993; 104:236-250. Seyfarth HJ, Hammerschmidt S, et al.(2007) Long-term bosentan in chronic thromboembolic pulmonary hypertension. Respiration, 2007; 74:287-92. Shaw PS, Ohlsson A.(2007) Sildenafil for pulmonary hypertension in neonates. Cochrane Database of Systematic Reviews 2007:CD005494. Shiyanagi S, Okazaki T, et al.(2008) Management of pulmonary hyper-tension in congenital diaphragmatic hernia: nitric oxide with prostaglandin-E1 versus nitric oxide alone. Pediatr Surg Int, 2008; 24:1101-4. Sildenafil for Treatment of Pulmonary Arterial Hypertension. Hayes Alert Newsletter. VII:12; 2004. Simonneau G, Barst RJ, et al.(2002) Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized placebo-controlled trial. Am J Respir Crit Care Med, 2002; 165:800-4/ Simonneau G, Galie N, et al.(2004) Clinical classification of pulmonary hypertension. J Am Coll Cardiol, 2004; 43(12 suppl S):5S-12S. Simonneau G, Galie N, Jansa P, et al.(2014) Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients Int J Cardiol. Mar 15 2014;172(2):332-339. PMID 24525158 Simonneau G, Galie N, Jansa P, et al.(2014) Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients. Int J Cardiol. Mar 15 2014;172(2):332-339. PMID 24525158 Simonneau G, Gatzoulis MA, Adatia I, et al(2013) Updated clinical classification of pulmonary hypertension J Am CollCardiol. Dec 24 2013; 62(25 Suppl): D34-41. PMID 24355639 Simonneau G, Montani D, Celermajer DS, et al(2019) Haemodynamic definitions and updated clinical classification of pulmonary hypertension Eur Respir J. 2019; 53(1) Simonneau G, Rubin LJ, et al.(2008) Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary hypertension. Ann Int Med, 2008; 149:321-30. Skoro-Sajer N, Bonderman D, et al.(2007) Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. J Thromb Heamost, 2007; 5:483-9. Skoro-Sajer N, Lang I.(2014) Extended-release oral treprostinil for the treatment of pulmonary arterial hypertension. Expert Rev Cardiovasc Ther. Dec 2014;12(12):1391-1399. PMID 25363827 Skoro-Sajer N, Lang I.(2014) Extended-release oral treprostinil for the treatment of pulmonary arterial hypertension. Expert Rev Cardiovasc Ther. Dec 2014;12(12):1391-1399. PMID 25363827 Tapson VF, Jing ZC, Xu KF, et al.(2013) Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. Sep 2013;144(3):952-958. PMID 23669822 Tapson VF, Jing ZC, Xu KF, et al.(2013) Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. Sep 2013;144(3):952-958. PMID 23669822 Tapson VF, Torres F, Kermeen F, et al.(2012) Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. Dec 2012;142(6):1383-1390. PMID 22628490 Tapson VF, Torres F, Kermeen F, et al.(2012) Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. Dec 2012;142(6):1383-1390. PMID 22628490 U.S. Food and Drug Administration (FDA).(2013) Orenitram (treprostinil) extended release tablets: medical review(s). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203496Orig1s000TOC.cfm. Accessed February 4, 2015. U.S. Food and Drug Administration (FDA).(2015) Orenitram (treprostinil) extended release tablets: medical review(s). ). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203496Orig1s000TOC.cfm. Accessed February 4, 2015. United Therapeutics Corp.(2014) Orenitram® (treprostinil) extended-release tablets for oral use: prescribing information, October 2014. http://www.orenitram.com/dtc/index. Accessed February 3, 2015. United Therapeutics Corp.(2014) Orenitram® (treprostinil) extended-release tablets for oral use: prescribing information, October 2014. http://www.orenitram.com/dtc/index. Accessed February 3, 2015. USPDI, 2007 Watanabe H, et al.(2002) Sildenafil for primary and secondary pulmonary hypertension. Clin Pharmacol Ther 2002; 72:398-402. Zeng WJ, Xiong CM, Zhao L, et al.(2012) Atorvastatin in pulmonary arterial hypertension (APATH) study. Eur Respir J. Jul 2012;40(1):67-74. PMID 22362846 |
|
|
|
|
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association. |
|