Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension

Abstract

The safety and efficacy of adding bosentan to sildenafil in pulmonary arterial hypertension (PAH) patients was investigated.In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable sildenafil (⩾20 mg three times daily) for ⩾3 months were randomised (1:1) to placebo or bosentan (125 mg twice daily). The composite primary end-point was the time to the first morbidity/mortality event, defined as all-cause death, hospitalisation for PAH worsening or intravenous prostanoid initiation, atrial septostomy, lung transplant, or PAH worsening. Secondary/exploratory end-points included change in 6-min walk distance and World Health Organization functional class at 16 weeks, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time, and all-cause death.Overall, 334 PAH patients were randomised to placebo (n=175) or bosentan (n=159). A primary endpoint event occurred in 51.4% of patients randomised to placebo and 42.8% to bosentan (hazard ratio 0.83, 97.31% CI 0.58-1.19; p=0.2508). The mean between-treatment difference in 6-min walk distance at 16 weeks was +21.8 m (95% CI +5.9-37.8 m; p=0.0106). Except for NT-proBNP, no difference was observed for any other end-point. The safety profile of bosentan added to sildenafil was consistent with the known bosentan safety profile.In COMPASS-2, adding bosentan to stable sildenafil therapy was not superior to sildenafil monotherapy in delaying the time to the first morbidity/mortality event. @ERSpublications COMPASS-2: adding bosentan was not superior to sildenafil alone in delaying time to first morbidity/mortality event http://ow.ly/NiM65

Aspects of Modern Combination Specific Therapy of Pulmonary Arterial Hypertension: the Pros and Cons

“…Событием заболеваемости/ смертности считались случаи смерти по любой причине, госпитализации по причине ухудшения ЛАГ или инициа-ции внутривенных простаноидов, потребность в проведе-нии атриосептостомии, трансплантации легких или ухуд-шение симптомов ЛАГ [15]. Вторичные конечные точки включали: динамику Д6МХ к концу 16 недели; динамику ФК по ВОЗ к концу 16-й недели; время до первого события смерти по любой причине, госпитализацию по поводу ЛАГ или начало внутривенной терапии простаноидами, атрио-септостомии, или трансплантация легких; смерть по любой причине.…”

“…Пациенты характеризовались исходной Д6МХ 150-480 метров и должны были получать стабильную терапию силденафилом ≥20 мг 3 раза в день, по крайней мере 3 месяца до рандомизации. Иная ЛАГ-специфическая тера-пия не должна была применяться в течение 3 месяцев до рандомизации [15].…”

“…В период с 2006 по 2012 г. всего в РКИ было включе-но 334 пациента в 83 центрах из 13 стран: 175 из них были рандомизированы в группу плацебо,159 -в группу бозентана [15]. В этих группах все исходные характери-стики были сопоставимыми.…”

Navigating the uncharted waters of combination therapy in pulmonary arterial hypertension: COMPASS or dead-reckoning

“…Unlike these common diseases, however, PAH is considered an "orphan" disease, making large-scale clinical trials of multiple therapies more challenging, both logistically and practically [2,3]. Two articles in this issue of the European Respiratory Journal provide new information regarding the effects of adding a second approved oral medication to PAH patients who are not achieving a satisfactory clinical response to initial oral monotherapy [4,5].The COMPASS trial [4] enrolled 334 subjects over 6 years who were failing on first line therapy with sildenafil into a randomised trial to receive either the addition of bosentan 125 mg twice daily or placebo. The primary end-point was the time to first composite end-point of morbidity and mortality.…”

“…The COMPASS trial [4] enrolled 334 subjects over 6 years who were failing on first line therapy with sildenafil into a randomised trial to receive either the addition of bosentan 125 mg twice daily or placebo. The primary end-point was the time to first composite end-point of morbidity and mortality.…”