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Pulmonary Vascular Disease |

Effect of Bosentan and Sildenafil Combination Therapy on Morbidity and Mortality in Pulmonary Arterial Hypertension (PAH): Results From the COMPASS-2 Study FREE TO VIEW

Vallerie McLaughlin; Richard Channick; Hossein-Ardeschir Ghofrani; Jean-Christophe LeMarie; Robert Naeije; Milton Packer; Rogério Souza; Victor Tapson; Jonathan Tolson; Marius Hoeper
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University of Michigan Health System, Ann Arbor, MI


Chest. 2014;146(4_MeetingAbstracts):860A. doi:10.1378/chest.1992777
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Abstract

SESSION TITLE: Pulmonary Hypertension

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 28, 2014 at 02:45 PM - 04:15 PM

PURPOSE: Combining drugs that target different pathophysiological pathways is a recommended treatment strategy in PAH [1]. COMPASS-2 investigated the safety and efficacy of adding bosentan in PAH patients already receiving sildenafil.

METHODS: In this double-blind, placebo-controlled, Phase IV, add-on, event-driven study, patients with symptomatic PAH receiving stable dose sildenafil (≥20mg TID) for at least 12 weeks were randomized (1:1) to receive placebo or bosentan (125mg BID). The primary endpoint was time to first morbidity or mortality (M/M) event, defined as death, hospitalization for PAH worsening or intravenous prostanoid initiation, atrial septostomy, lung transplant, or worsening PAH.

RESULTS: 334 patients with PAH were randomized to placebo (n=175) or bosentan (n=159). The primary endpoint of time to first M/M event was not met, with an observed risk reduction of 17% versus placebo (p=0.25; log-rank). Amongst the secondary and planned exploratory endpoints, the mean placebo corrected treatment effect on 6MWD at 16 weeks was +21.8m (CI95% 5.9, 37.8), and a repeated measures analysis showed NT-proBNP levels over 20 months 23.5% (CI95% 33.7, 11.8) lower in the bosentan group relative to the placebo group. No difference was observed between treatment groups for any other endpoints. The safety profile of bosentan on top of sildenafil was consistent with the known profile of bosentan, with no new signals observed. Over a median double-blind treatment exposure of 23.3 months to placebo and 22.7 months to bosentan, aspartate and/or alanine aminotransferase elevations >3X upper limit of normal were 6.4% and 21.8% respectively.

CONCLUSIONS: In COMPASS-2, addition of bosentan in PAH patients treated with sildenafil did not significantly prolong the time to first M/M event. Improvements in 6MWD and NT-proBNP were observed. The known safety profile of bosentan was confirmed.

CLINICAL IMPLICATIONS: The study results support the importance of prospective clinical trials to determine optimal treatment strategies for PAH. 1. Galiè N, Corris PA, Frost A et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D60-72.

DISCLOSURE: Vallerie McLaughlin: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Gilead, United Therapeutics, Grant monies (from industry related sources): Actelion, Bayer, Ikaria, Novartis, United Therapeutics Richard Channick: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Grant monies (from industry related sources): Actelion, United Therapeutics Hossein-Ardeschir Ghofrani: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Ergonex, Gilead Sciences, GSK, Novartis, Pfizer, Grant monies (from industry related sources): Actelion, Bayer, Ergonex, Pfizer Jean-Christophe LeMarie: Other: Provided statistical support, funded by Actelion Robert Naeije: Grant monies (from industry related sources): Actelion, Pzizer, Consultant fee, speaker bureau, advisory committee, etc.: Actelio, Lung RX, Bayer, GSK Milton Packer: Consultant fee, speaker bureau, advisory committee, etc.: Actelion Rogério Souza: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Eli Lilly, Bayer, GSK Victor Tapson: Grant monies (from industry related sources): Actelion, Bayer, Gilead, Novartis, United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Gilead, Novartis, United Therapeutics Jonathan Tolson: Employee: Actelion Marius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Pfizer, Novartis

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