This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutic Subcommittee. Class: Pulmonary Arterial Hypertension agents Non-Formulary Drugs: Epoprostenol (Flolan, Veletri), Treprostinil (Remodulin, Tyvasoinhaled, Orenitram-tablet), Sildenafil (Revatio), Tadalafil (Adcirca), Iloprost (Ventavis), Bosentan (Tracleer), Ambrisentan (Letairis), Macitentan (Opsumit), Riociguat (Adempas), Selexipag (Uptravi) Effective Date: February 17, 2016 Revision Date: February 17, 2016 LOB: Non-Medicare Only Policy/Criteria: 1. Phosphodiesterase Type 5 Enzyme Inhibitors: Sildenafil (Revatio), Tadalafil (Adcirca) a. Pulmonary arterial hypertension: WHO Functional Class II or above b. Sildenafil (Revatio) is the non-formulary preferred PDE-5 inhibitor 2. Endothelin Receptor Antagonist: Bosentan (Tracleer), Ambrisentan (Letairis), Macitentan (Opsumit) a. Pulmonary arterial hypertension: WHO Functional Class II or above b. Failure or contraindication to one of the phosphodiesterase type 5 enzyme inhibitors 3. Soluble Guanylate Cyclase Stimulators: Riociguat (Adempas) a. Pulmonary arterial hypertension: WHO Functional Class II or above b. Failure or contraindication to one of the phosphodiesterase type 5 enzyme inhibitors 4. Parenteral Vasodilators: Epoprostenol (Flolan, Veletri), Treprostinil (Remodulin) a. Pulmonary arterial hypertension: WHO Functional Class III with evidence of rapid progression of disease or documented markers of poor clinical prognosis OR WHO Functional Class IV b. Must be prescribed by a cardiologist or a pulmonologist 5. Inhaled Vasodilators: Iloprost (Ventavis), Treprostinil (Tyvaso-inhaled) a. Pulmonary arterial hypertension: WHO Functional Class III OR WHO Functional Class IV b. Unable to manage parental prostanoid therapy
6. Oral Prostacyclin Analogues: Treprostinil (Orenitram-tablet), Selexipag (Uptravi) a. Pulmonary arterial hypertension: WHO Functional Class III with evidence of rapid progression of disease or documented markers of poor clinical prognosis OR WHO Functional Class IV b. Unable to manage parental prostanoid therapy Clinical Justification: Phosphodiesterase Type 5 Enzyme Inhibitors: Sildenafil (Revatio), Tadalafil (Adcirca) Inhibition of the antiproliferative effects of the PDE-5 pathway, which regulates cyclic guanosine monophosphate hydrolysis, may be significant in the long-term treatment of pulmonary hypertension. Endothelin Receptor Antagonist: Bosentan (Tracleer), Ambrisentan (Letairis), Macitentan (Opsumit) Endothelin receptor antagonists (ERAs) are therapeutic alternatives to parenteral prostacyclin agents. Given orally, they competitively bind to endothelin 1 (ET-1) receptors endothelin-a and endothelin-b, causing a reduction in pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP). This agent is indicated for treatment of PAH in patients with WHO class II or III symptoms to improve exercise ability and decrease the rate of clinical deterioration. Soluble Guanylate Cyclase Stimulators: Riociguat (Adempas) Soluble guanylate cyclase (sgc) is an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). Pulmonary arterial hypertension (PAH) is associated with endothelial dysfunction, impaired synthesis of NO, and insufficient stimulation of the NO-sGC-cGMP pathway. Parenteral Vasodilators: Epoprostenol (Flolan, Veletri), Treprostinil (Remodulin) Parenteral vasodilators are used for patients whose IPAH fails to respond to calcium channel blockers or who cannot tolerate these agents and who have New York Heart Association (NYHA) type III or IV right-sided heart failure. Inhaled Vasodilators: Iloprost (Ventavis), Treprostinil (Tyvaso-inhaled) Inhaled prostacyclin (PGI 2 ) synthetic analogues are an alternative to parenteral administration. They are used in an attempt to limit systemic adverse effects. Oral Prostacyclin Analogues: Treprostinil (Orenitram-tablet), Selexipag (Uptravi) Oral prostacyclin (PGI2) synthetic analogues are an alternative to parenteral administration.
Clinical pulmonary hypertension characterized into 5 groups by pathological features (Endorsed by the ECS/ERS guidelines)
Pulmonary hypertension classification after the NYHA functional classification according to the WHO (Endorsed by the ECS/ERS guidelines)
Updated treatment algorithm of Pulmonary Arterial Hypertension: Journal of American College of Cardiology, 2013
2014 CHEST: Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults For treatment naïve PAH patients with WHO FC I symptoms, we suggest continued monitoring for the development of symptoms that would signal disease progression and warrant the initiation of pharmacotherapy Patients with PAH, in the absence of right-heart failure or contraindications to CCB therapy, demonstrate acute vasoreactivity according to consensus definition, should be considered candidates for a trial of therapy with oral CCB blocker For treatment naïve PAH patients with WHO FC II symptoms who are not candidates for, or who have failed CCB therapy, we advise monotherapy be initiated with a currently approved endothelin receptor antagonist, phosphodiesterase-5 inhibitor, or the soluble guanylate cyclase stimulator For treatment naïve PAH patient with WHO FC III symptoms who are not candidates for, or who have failed CCB therapy, we advised monotherapy be initiated with a currently approve endothelin receptor antagonist, phosphodiesterase-5 inhibitor, or the soluble guanylate cyclase stimulator For PAH patients in WHO FC III who have evidence of progression of their disease, and/or markers of poor clinical prognosis despite treatment with one or two classes of oral agents, we advise consideration of the addition of parental or inhaled prostanoid For treatment naïve PAH patients in WHO FC IV, we advise initiation of monotherapy with a parenteral prostanoid agent For treatment naïve PAH patients in WHO FC IV who are unable or do not desire to manage parental prostanoid therapy, we advise treatment with an inhaled prostanoid in combination with an endothelin receptor antagonist For WHO FC III or IV PAH patients with unacceptable clinical status despite established PAH-specific monotherapy, we advise addition of a second class of PAH therapy to improve exercise capacity.
Reference: 1. CHEST: Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults. CHEST Guideline and Expert Panel Report. June 17, 2014 2. Updated Treatment Algorithm of Pulmonary Arterial Hypertension. Galie et al. Journal of the American College of Cardiology. 2013;62:D60-72 3. 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 and of European Respiratory Society. European Heart Journal. 2015 4. Primary Pulmonary Hypertension Medication. Oudiz et al. Medscape. Updated Oct 30, 2015 5. Uptravi (Selexipag) package insert 2015