Coverage for treatment of pulmonary hypertension is determined according to individual or group customer benefits. 

A diagnosis of pulmonary hypertension is substantiated by results from Doppler echocardiography and/or direct measurement of pulmonary arterial pressure. Pulmonary arterial hypertension is defined as a mean pulmonary arterial pressure of greater than or equal to 25 mmHg, with a pulmonary capillary wedge pressure of less than 15 mmHg.

The patient must meet the criteria specific to the individual drug as listed below.

Epoprostenol sodium (Flolan®)
Treatment with continuous intravenous infusion of epoprostenol sodium (Flolan®)(J1325) is covered for patients who meet the following criteria:

1. Primary pulmonary hypertension (416.0) and associated New York Heart Association Class III or IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).
   
   
2. Secondary pulmonary hypertension (416.8) related to congenital heart disease and associated New York Heart Association Class III or IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).
   
   
3. Secondary pulmonary hypertension (416.8) related to connective tissue diseases (i.e., scleroderma, CREST syndrome, systemic lupus erythematosus) and associated New York Heart Association Class III or IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).

Treprostinil (Remodulin®)
Treatment with continuous subcutaneous infusion of treprostinil (Remodulin®)(J3285) is covered for patients who meet the following criteria:

1. Primary pulmonary hypertension (416.0) and associated New York Heart Association Class II, III or IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).
   
   
2. Secondary pulmonary hypertension (416.8) related to congenital heart disease and associated New York Heart Association Class II, III or IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).
   
   
3. Secondary pulmonary hypertension (416.8) related to connective tissue diseases (i.e., scleroderma, CREST syndrome, systemic lupus erythematosus) and associated New York Heart Association Class II, III or IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).

Iloprost (Ventavis®)
Treatment with inhalation administration of iloprost (Ventavis®)(Q4080) is covered for patients who meet the following criteria:

1. Primary pulmonary hypertension (416.0) and New York Heart Association (NYHA) Class III or Class IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).
   
   
2. Secondary pulmonary hypertension (416.8) related to collagen vascular disease, congenital systemic-to-pulmonary shunt, portal hypertension, Human Immunodeficiency Virus (HIV) infection, drugs and toxins, and appetite suppressants; and persistent pulmonary hypertension of the newborn and New York Heart Association (NYHA) Class III or Class IV symptoms that do not respond adequately to conventional therapy (e.g., oral vasodilator therapy).
   

Ventavis has not been studied in children under the age of 18.

Ventavis is formulated for inhalation only via the Prodose® Adaptive Aerosol Delivery (AAD) System (K0730). On August 24, 2005, the I-Neb Adaptive Aerosol Delivery (AAD) System was FDA approved as an additional drug delivery system.

Bosentan (Tracleer^TM), Ambrisentan (Letairis™ ) and sildenafil (Revatio^TM) are indicated for the treatment of pulmonary hypertension and are only available through the retail prescription drug benefit.

Bosentan, ambrisentan, or sildenafil may be used alone or in combination with calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics, digoxin, and anticoagulants, but will not be covered when used concomitantly with bosentan (Tracleer^TM), ambrisentan (Letairis™), sildenafil (Revatio^TM), epoprostenol sodium (Flolan®), treprostinil sodium (Remodulin®), or iloprost (Ventavis®), due to the lack of clinical data to support combination therapy with these agents.

Flolan, Remodulin, and Ventavis do not have FDA approval to be used as combination therapy with each other.

Currently there is no established criterion or algorithm for the transitioning of patients from one pulmonary hypertension drug product to another (e.g., sildenafil to bosentan). To accommodate potential overlapping titration schedules when changing therapy from one drug product to another the use of two agents concomitantly may be authorized for a period of up to one month. Coverage will not be provided for the use of two agents (bosentan, ambrisentan, sildenafil, epoprostenol, iloprost, treprostinil) as maintenance combination therapy for pulmonary hypertension.

Refer to the Text Attachment below for New York Heart Association Classifications.

Any use for conditions other than those with FDA approval will be denied as not medically necessary, and therefore, not covered. A participating, preferred, or network provider cannot bill the member for the denied service. 

Refer to Medical Policy Bulletin E-17 for information on portable (external) infusion pumps.

Description

Epoprostenol sodium (Flolan® ) is a naturally occurring prostacyclin that decreases pulmonary vascular resistance and increases cardiac output.  It is administered as a continuous intravenous infusion. Surgical implantation of a central venous access device is required. A backup pump is utilized to assure continuous administration. Flolan has a rapid onset of action, within seconds of infusion, and has a short half-life of approximately six minutes. The medication must be kept cold at all times during administration with ice packs to cool the pump cassette.

Treprostinil (Remodulin®) is a prostacyclin analogue that decreases pressure in the pulmonary artery, causing patients to experience significant improvements in the signs and symptoms of this disease. It is administered as a continuous, subcutaneous infusion. The patient is taught to self-administer via a MiniMed 407C infusion pump. Two pumps are required to ensure continuous delivery of the therapy. This is necessary and even critical since interruption in the infusion may cause the patient to begin to experience rebound symptoms. Remodulin is chemically stable at room temperature and has a half-life of three hours.

Iloprost (Ventavis®) is an inhaled formulation of iloprost, a synthetic prostacyclin analogue. Inhaled iloprost acts as a vasodilator directly on the pulmonary arterial circulation to lower pulmonary artery pressure and improve cardiac output and oxygen saturation. The effects of the inhaled drug last approximately 60 minutes; therefore, multiple inhalations are required daily.

NOTE:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Under the Federal Employee Program, all services that utilize FDA-approved drugs, devices, or biological products are eligible when intended for the treatment of a serious or life-threatening condition and when medically necessary and appropriate for the patient's condition.

Flolan, Physician's Desk Reference, Edition 55, 2001, Medical Economics Company, Inc.

USPDI, Vol.1, Edition 24, 2004, Micromedex, Inc.

United Therapeutics Corporation, Remodulin® (treprostinil), Product Information, United Therapeutics; March, 2002

CoTherix^TM, Ventavis® (iloprost), Product Information, CoTherix, Inc.; 2005

Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2, European Respiratory Journal, Vol. 24, No. 3, 2004

Combination therapy for pulmonary arterial hypertension: Still more questions than answers, European Respiratory Journal, Vol. 24, No. 3, 2004

Efficacy and Safety of Sildenafil Added to Treprostinil in Pulmonary Hypertension, American Journal of Cardiology, Vol. 95, 2006

Randomized Study of Adding Inhaled Iloprost to Existing Bosentan in Pulmonary Arterial Hypertension, American Journal of Respiratory and Critical Care Medicine, Vol. 174, No. 11, 12/2006

Combination Therapy and New Types of Agents for Pulmonary Arterial Hypertension, Clinics in Chest Medicine, Vol. 28, 2007

In 1928, the New York Heart Association published a classification of patients with cardiac disease based on clinical severity and prognosis. This classification has been updated in seven subsequent editions of Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels (Little, Brown & Co.). The ninth edition, revised by the Criteria Committee of the American Heart Association, New York City Affiliate, was released March 4, 1994. The new classifications are summarized below:

Functional Capacity

Class I. Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain.

Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Objective Assessment

1. No objective evidence of cardiovascular disease
2. Objective evidence of minimal cardiovascular disease
3. Objective evidence of moderately severe cardiovascular disease
4. Objective evidence of severe cardiovascular disease