Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension.

Background— Ambrisentan is a propanoic acid–based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension. Methods and Results— Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m ( P =0.008) and 51 m ( P <0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m ( P =0.022) and 59 m ( P 3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m. Conclusions— Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.

According to current guidelines, pulmonary arterial hypertension (PAH) is diagnosed when mean pulmonary arterial pressure (P̄_pa) exceeds 25 mmHg at rest or 30 mmHg during exercise. Issues that remain unclear are the classification ofP̄_pavalues 30 mmHg during exercise is always pathological.We performed a comprehensive literature review and analysed all accessible data obtained by right heart catheter studies from healthy individuals to determine normalP̄_paat rest and during exercise. Data on 1,187 individuals from 47 studies in 13 countries were included. Data were stratified for sex, age, geographical origin, body position and exercise level.P̄_paat rest was 14.0±3.3 mmHg and this value was independent of sex and ethnicity. RestingP̄_pawas slightly influenced by posture (supine 14.0±3.3 mmHg, upright 13.6±3.1 mmHg) and age (<30 yrs: 12.8± 3.1mmHg; 30–50 yrs: 12.9±3.0 mmHg; ≥50 yrs: 14.7±4.0 mmHg).P̄_paduring exercise was dependent on exercise level and age. During mild exercise,P̄_pawas 19.4±4.8 mmHg in subjects aged <50 yrs compared with 29.4±8.4 mmHg in subjects ≥50 yrs (p<0.001).In conclusion, whileP̄_paat rest is virtually independent of age and rarely exceeds 20 mmHg, exerciseP̄_pais age-related and frequently exceeds 30 mmHg, especially in elderly individuals, which makes it difficult to define normalP̄_pavalues during exercise.