• mean pulmonary artery pressure (PAP) of more than 30 mm Hg with exercise;
• mean PAP of more than 25 mm Hg at rest;
• exclusion of left-sided cardiovascular disease, myocardial disease, congenital heart disease, or clinically important respiratory, connective tissue, or chronic thromboembolic diseases.

• Diagnosis of pulmonary hypertension has been confirmed by right heart catheterization, AND
• Member has pulmonary hypertension with World Health Organization (WHO)/New York Heart Association (NYHA) class III to IV symptoms (for treprostinil sodium, members who are WHO/NYHA class II symptoms are also eligible) (see appendix A) OR
• For members requesting intravenous sildenafil, member has pulmonary hypertension with NYHA class II-III symptoms (see appendix A) AND
  • Member is currently prescribed oral sildenafil for continued PAH treatment and is temporarily unable to take oral medication; AND
  • Member is not currently taking another phosphodiesterase-5 inhibitor; AND
• Member has PAH due to any of the causes listed in WHO group 1 classification (See appendix B) AND
• The member does not have any FDA labeled contraindications to the requested agent; AND
• The prescriber is a specialist in the area of the patient’s diagnosis (e.g. cardiologist, pulmonologist) or has consulted with a specialist in the area of the patient’s diagnosis

[INFORMATIONAL NOTE:
According to the ACCP and ACCF/AHA practice guidelines, right-heart catheterization is required to confirm the presence of pulmonary hypertension, establish the specific diagnosis, and determine the severity of pulmonary hypertension and to guide therapy. Doppler echocardiography should be performed as a noninvasive screening test that can detect pulmonary hypertension, though it may be imprecise in determining actual pressures compared to invasive evaluation in a portion of patients.
In a 12-week study by Barst, et al. patients receiving continuous IV infusion of epoprostenol had improvements in exercise capacity, WHO functional class, and quality of life; however survival advantage has yet to be determined.]

• Continuous administration of epoprostenol sodium (i.e. Flolan, Veletri) with a portable infusion pump attached to a permanent indwelling central venous catheter when patient has NYHA functional class III or IV symptoms;
  • Epoprostenol sodium (Veletri) - Infusion of Veletri should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established
  • Epoprostenol sodium (Flolan) - Initiate intravenous infusion through a central venous catheter at 2 ng/kg/min. Change dose in 1-to 2-ng/kg/min increments at intervals of at least 15 minutes based on clinical response.
• Continuous intravenous or subcutaneous infusion of treprostinil sodium (i.e. Remodulin) when patient has NYHA functional class II to IV symptoms;
  • Treprostinil sodium (Remodulin) - Initial dose for new to prostacyclin infusion therapy: 1.25 ng/kg/min; increase based on clinical response (increments of 1.25 ng/kg/min per week for the first 4 weeks of treatment, later 2.5 ng/kg/min per week). Avoid abrupt cessation.
• Inhalation of treprostinil (i.e. Tyvaso) with pulmonary delivery device in patients with NYHA functional Class III symptoms;
  • Treprostinil (Tyvaso) - Administer undiluted, as supplied. A single breath of Tyvaso delivers approximately 6 mcg of treprostinil. Administer in 4 separate treatment sessions each day approximately four hours apart, during waking hours. Initial dosage: 3 breaths (18 mcg) per treatment session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths. Dosage should be increased by an additional 3 breaths per session at approximately 1-2 week intervals, if tolerated. Titrate to target maintenance dosage of 9 breaths or 54 mcg per treatment session as tolerated
• Inhalation of iloprost (i.e. Ventavis) with pulmonary drug delivery device in patients with NYHA functional Class III or IV symptoms and inhalation of treprostinil (i.e. Tyvaso) with pulmonary delivery device in patients with NYHA functional Class III symptoms.
  • Iloprost (Ventavis) - Initially, 2.5 mcg (as delivered at the mouthpiece via the I-neb AAD system). If well tolerated, the dose may be increased and maintained at 5 mcg. Inhaled iloprost should be administered 6 to 9 times daily, but no more than every 2 hours, during waking hours; based on individual need and tolerability
• Intravenous bolus of sildenafil (i.e. Revatio) three times daily when patient has with NYHA Functional Class II–III symptoms
  • Sildenafil (Revatio) - 2.5 mg or 10 mg three times a day administered as an intravenous bolus injection
• 
  [INFORMATIONAL NOTE: Candidates for epoprostenol and bosentan therapy include those with New York Heart Association Class III or Class IV symptoms who are refractory to other therapies. Epoprostenol, available under the trade names Flolan and Veletri, have differences between their formulations. Veletri is available as a first generation and second generation formulation, which vary in vial strength, differences in storage and stability, and differences in dilution and reconstitution concentrations that can affect infusion rates. Candidates for treprostinil sodium also include those with Class II-IV symptoms. Bosentan is indicated for patients with functional class III and IV to improve exercise ability and decrease clinical worsening. Macitentan is indicated for WHO Group 1 PAH in patients with WHO Functional Class II-III symptoms as monotherapy or in combination with phosphodiesterase (PDE)-5 inhibitors or inhaled prostanoids. Macitentan is also indicated for patients with idiopathic and heritable PAH, PAH caused by connective tissue disorders, and PAH caused by congenital heart disease with repaired shunts. Iloprost is indicated for WHO (World Health Organization) Group I pulmonary arterial hypertension in patients with NYHA Class III or IV symptoms and treprostinil is indicated for WHO Group I pulmonary arterial hypertension in patients with NYHA Class III symptoms. Sildenafil and tadalafil are indicated for patients with pulmonary arterial hypertension WHO Group I. Riociguat is indicated for patients with persistent/recurrent CTEPH, WHO Group 4, after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class. Riociguat is also indicated for patients with pulmonary arterial hypertension WHO Group 1; with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue disease as monotherapy or in combination with ERAs or prostanoids, to improve exercise capacity, WHO functional class, and to delay clinical worsening.]

• Member has had clinical benefit with the requested agent
• Member has not experienced any unacceptable toxicities to the requested agent

• ischemic vascular disease without pulmonary hypertension,
• congestive heart failure without pulmonary hypertension,
• chronic obstructive lung disease without pulmonary hypertension,
• angina,
• cardiopulmonary bypass operation,
• nitric oxide withdrawal,
• achalasia,
• secondary Raynaud’s phenomenon,
• claudication
• peripheral ischemia
• pulmonary hypertension in pediatric patients
• left ventricular systolic dysfunction
• digital ulcers
• idiopathic pulmonary fibrosis
• Eisenmenger Syndrome (with the exception of bosentan)
• recurrent glioblastoma
• radiographic contrast agent for nephropathy prophylaxis
• pulmonary hypertension vasoreactivity-testing (iloprost)
• transient oedema
• short-term treatment of pulmonary hypertension
• Acute Kidney Failure
• Type 2 Diabetes
• Subarachnoid Hemorrhage
• COPD
• One Lung Anesthesia
• Severe Traumatic Brain Injury
• Ischemia Reperfusion Injury
• Systemic Sclerosis
• Interstitial Lung Disease
• Combined Pulmonary Fibrosis and Emphysema
• Acute Respiratory Distress Syndrome
• Hypoxic Pulmonary Vasoconstriction
• Traumatic brain injury
• Migraine

• Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatique, palpitation, or dyspnea (shortness of breath)
• Class II: Slight limitation of physical activity. Ordinary physical activity results in symptoms.
• Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms.
• Class IV: Unable to engage in any physical activity without discomfort. Symptoms may be present even at rest.

• WHO Group 1. Pulmonary Arterial Hypertension (PAH)

1.2.2 Activin receptor-like kinase type 1 (ALK1), endoglin (with or without hereditary hemorrhagic telangiectasia) ENG, SMAD9, CAV1, KCNK3

1.6 Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)

· WHO Group 2. Pulmonary Hypertension Owing to Left Heart Disease

2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies

· WHO Group 3. Pulmonary Hypertension due to Lung Disease and/or Hypoxia

• WHO Group 4. Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• WHO Group 5. Pulmonary Hypertension with Unclear Multifactorial Mechanisms

5.2 Systemic disorders: Sarcoidosis, Pulmonary histiocytosis, Langerhans cell histiocytosis
(lymphangioleiomyomatosis, neurofibromatosis, vasculitis)

5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis, segmental PH

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Non Oral Drug Therapy for Pulmonary Hypertension
Drug Therapy of Pulmonary Hypertension
Bosentan (Tracleer)
Endothelin Receptor Antagonist
Epoprostenol (Flolan and Veletri)
Flolan (Epoprostenol Sodium)
Prostacyclin
Remodulin (treprostinil Sodium)
Tracleer (Bosentan)
Treprostinil Sodium (Remodulin)
Sildenafil (Revatio)
Revatio (sildenafil)
Ventavis (iloprost)
Iloprost (Ventavis)
Ambrisentan (Letairis)
Letairis (ambrisentan)
Tyvaso (treprostinil)
Treprostinil (Tyvaso)
Taladafil (Adcirca)
Adcirca (taladafil)
Veletri (Epoprostenol)
Macitentan (Opsumit)
Opsumit (macitentan)
Riociquet (Adempas)
Adempas (riociquet)

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Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

J1325
J3285
J7686
J7699
J8499
Q4074
S0155
S0090