Tracleer consistently reduced the rate of
clinical worsening in all 3 pivotal studies

EARLY (FC II) 77% relative risk reduction in clinical worsening at month 6^*1-3

Clinical worsening defined as1:   Death   Hospitalization due to PAH   Symptomatic progression of PAH† At week 243:   7.6% absolute risk reduction

Study 351 (FC III) 100% of Tracleer patients were event-free at week 32⁴

Clinical worsening defined as4:   Right ventricular heart failure   Aggravated pulmonary hypertension

BREATHE-1 (FC III-IV) 71% relative risk reduction at week 28^2,3,5

Clinical worsening defined as5:   Death   Hospitalization related to PAH   Discontinuation of therapy   Initiation of epoprostenol therapy At week 283,5:   26% absolute risk reduction

FC functional class; NNT number needed to treat.

*All patients (n=80, Tracleer; n=77, placebo) participated in the first 24 weeks. Observations for up to 32 weeks were recorded in some patients (n=15, Tracleer; n=9, placebo). Patients experiencing worsening events: n=3, Tracleer; n=13, placebo.¹

†Symptomatic progression of PAH was defined as the presence of 1 of the following: appearance or worsening of right heart failure (as assessed by the investigator), decrease ≥10% from baseline in two 6-minute walk tests performed ≥2 weeks apart, or ≥5% decrease from baseline in two 6-minute walk tests performed ≥2 weeks apart associated with ≥2-point increase in Borg dyspnea index.¹

‡NNT = 1 ÷ absolute risk reduction.

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 the clinical experience of Tracleer

EARLY Endothelin Antagonist tRial in miLdlY 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. Both the Tracleer group and the placebo group included some patients on sildenafil at baseline (Tracleer, n=14; placebo, n=15). Clinical worsening defined as death, hospitalization due to PAH, or symptomatic progression of PAH.¹

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). Clinical worsening defined as right ventricular heart failure or aggravated pulmonary hypertension.⁴

BREATHE-1 Multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of Tracleer (125 mg BID, 250 mg BID) in patients with WHO functional class III or IV pulmonary arterial hypertension (N=213). All patients (n=144 in the Tracleer group and n=69 in the control group) participated in the first 16 weeks. A subset of this population (n=35 in the Tracleer group and n=13 in the control group) continued for up to 28 weeks. Clinical worsening was defined as the combined endpoint of death, hospitalization for treatment related to PAH, discontinuation of therapy due to worsening PAH, or initiation of epoprostenol therapy.^3,5

1. 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.
2. Tracleer (bosentan) full prescribing information. Actelion Pharmaceuticals US, Inc. August 2009.
3. Data on file, Actelion Pharmaceuticals.
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. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002;346:896-903.