Bosentan for sarcoidosis-associated pulmonary hypertension, age-adjusted D-dimer levels in pulmonary embolism, and mean arterial blood pressure targets in septic shock.

Abstract

Pulmonary hypertension (PH) is present in a significant number of patients with advanced sarcoidosis, and is associated with increased mortality. Baughman and colleagues (1) performed a double-blind, randomized, placebo-controlled trial to determine whether bosentan is effective in treating sarcoidosis-associated PH. A total of 39 patients with sarcoidosis and pulmonary artery (PA) hypertension were randomized to receive either bosentan or placebo in a 2:1 ratio. Patients were excluded if they had severe exercise limitation (New York Heart Association class IV), severe airway obstruction, or significant heart failure. Right heart catheterization was performed before and after 16 weeks of therapy. Outcomes included the changes in mean PA pressure, 6-minute walk distance (6MWD), dyspnea, and quality of life as assessed by validated questionnaires. In the 30 patients with serial hemodynamic data, mean PA pressure decreased by 4 (66.6) mm Hg in the bosentan group (P , 0.02), and increased by 1 (63.7) mm Hg (P . 0.05) in the placebo group. There was no significant change in 6MWD, dyspnea, or quality of life scores in either group. Themajor limitation of this study is its emphasis on PA pressure. Changes in PA pressure correlate poorly with clinical outcomes. Contemporary studies of PH therapy generally emphasize functional outcomes, such as 6MWD (2). In this study, 6MWD decreased in the bosentan group (223 6 69.5 m; P . 0.05), whereas it increased in the placebo group (176 44.1; P. 0.05). Although not statistically significant, this difference, together with more frequent desaturation in the bosentan group, suggests that bosentan worsened gas exchange in some patients (3). In this study, 18 of 35 patients had fibrosis on chest radiograph, a forced vital capacity of less than 60%, or both. However, even a subgroup analysis of patients with forced vital capacity greater than 50% failed to demonstrate an increased 6MWD. Given the modest PH in this study (mean PA pressure, z35 mm Hg; mean right atrial pressure, 5 mm Hg), it is possible that patients with more severe PH (i.e., out of proportion to their fibrosis) would have experienced an increase in their exercise capacity. Until additional studies are performed, however, patients with sarcoidosis-associated PH should be referred to centers with expertise in PH and monitored closely for response to vasodilator therapy, if it is initiated (3). n