Tracleer improved hemodynamics in
mild to severe patients (FC II, III)

EARLY (FC II) Significantly improved in PVR, CI, and mPAP^2,3

Significantly improved CI   +0.24 L/min/m2 treatment effect; p<0.052,3

Significantly improved mPAP   –5.7 mm Hg treatment effect; p<0.052,3

Study 351 (FC III) Significantly improved 4 key hemodynamic parameters^3,4

CI Cardiac index RAP Right atrial pressure

*Parameter not available at baseline in 1 patient.

PVR Pulmonary vascular resistance PAP Pulmonary arterial pressure

*Parameter not available at baseline in 1 patient.

BREATHE-5 (Eisenmenger syndrome FC III) Significantly improved PVRi⁵

Note: In clinical studies of Tracleer, hemodynamics were not studied in FC IV patients.

CI cardiac index; FC functional class: mPAP mean pulmonary arterial pressure; PAP pulmonary arterial pressure; PVR pulmonary vascular resistance; RAP right atrial pressure.

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may preclude future use as their disease progresses.

Important safety information

Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.

Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter.

High potential for major birth defects—Pregnancy must be excluded and prevented through the use of reliable forms of birth control; monthly pregnancy tests should be obtained.

Contraindicated for use with cyclosporine A and glyburide.

Please see full prescribing information including BOXED WARNING.

Review how Tracleer improves and maintains FC status

EARLY Endothelin Antagonist tRial in miLdlY symptomatic PAH patients. The first and only randomized, double-blind, placebo-controlled trial conducted solely in mildly symptomatic (functional class II) patients with PAH (N=185). Patients were randomized to Tracleer (62.5 mg BID, 125 mg BID) or placebo. Trial duration was 6 months. Concomitant use of anticoagulants and calcium channel blockers was allowed. Baseline PVR: 839 ± 531 dyn•sec/cm⁵, Tracleer; 805 ± 531 dyn•sec/cm⁵, placebo. Baseline CI: 2.7 ± 0.8 L/min/m², Tracleer; 2.7 ± 0.6 L/min/m², placebo. Baseline mPAP: 52.5 ± 18.9 mm Hg, Tracleer; 52.3 ± 16.0 mm Hg, placebo. Both the Tracleer group and the placebo group included some patients on sildenafil at baseline (Tracleer, n=14; placebo, n=15).²

Study 351 Randomized, double-blind, placebo-controlled study of Tracleer 125 mg BID vs placebo in patients with WHO functional class III or IV pulmonary arterial hypertension (N=32).⁴

BREATHE-5 Randomized, double-blind, placebo-controlled trial in adults with PAH associated with Eisenmenger syndrome (N=54). Patients were randomized to Tracleer (62.5 mg BID, 125 mg BID) or placebo. Background therapies included anticoagulants, vasodilators, diuretics, and supplemental oxygen.⁵

1. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension. J Am Coll Cardiol. 2009;53:1573-1619.
2. Galiè N, Rubin LJ, Hoeper MM, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet. 2008;371:2093-2100.
3. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.
4. Channick RN, Simonneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet. 2001;358:1119-1123.
5. Galiè N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114:48-54.