Key Points:<\/p>\n
<\/p>\n
Macitentan and Tadalafil are frequently used in combination therapy for pulmonary arterial hypertension (PAH); however, a fixed-dose combination (with the potential to be taken as a single pill)\u00a0 has never been trialed against monotherapy. In a breaking presentation at the 2023 ACC Conference today, Dr. Kelly Chin (UTSW) and his team presented their study: \u201cEfficacy and safety of macitentan tadalafil fixed dose combination in pulmonary arterial hypertension: results from the randomized controlled phase III A DUE study.\u201d<\/p>\n
The DUE trial (NCT03904693) was prospective, multicenter, double-blind, randomized, active-controlled, adaptive Phase III study which evaluated the efficacy and safety of macitentan\/tadalafil FDC versus macitentan and tadalafil monotherapies in patients with PAH. Patients were randomized into one of three groups: macitentan 10 mg monotherapy, macitentan 10 mg \/ tadalafil 40 mg FDC, or tadalafil 40 mg monotherapy. The inclusion criteria comprised any adults WHO FC II or III PAH who were either treatment na\u00efve or on a stable dose of ERA or PDE5i for at least 3 months. The primary endpoint was change in PVR, expressed as ratio of baseline.<\/p>\n
A total of 187 patients were randomized: 35 in the macitentan arm, 44 in the tadalafil arm, and 108 in the FDC arm. The average age was 51, and 75% were women. 50% had idiopathic PAH. The primary outcome was change in PVR from baseline at Week 16. M\/T FDC therapy resulted in significantly lower PVR when compared to macitentan monotherapy (PVR reduction 29%, ratio of geometric means (95% CL): 0.71 (0.61, 0.82), P<0.0001) and tadalafil (PVR reduction 28%, ratio of geometric means (95% CL): 0.72 (0.64, 0.80), P<0.0001). The secondary endpoint of change in 6MWD at Week 16 was not significant between groups, but there was a trend towards improvement in the FDC arm. FDC therapy had a similar safety profile to both macitentan and tadalafil monotherapy with no additional serious adverse events.<\/p>\n
When discussing the clinical implications of the study at ACC, Dr. Chin stated: \u201cMacitentan\/tadalafil FDC was well tolerated and consistent with the safety profile of macitentan and tadalafil\u2026DUE supports M\/T FDC, as a single-tablet combination therapy, for initial dual combination therapy and rapid escalation, in line with the ESC\/ERS 2022 guidelines on the use of dual combination therapy in PAH.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
Key Points: Macitentan and Tadalfil are frequently used in combination for PAH, which opens up the possibility of a fixed-dose combination pill. In the DUE study, macitentan\/tadalafil FDC therapy was compared against macitentan and tadalafil monotherapy. The primary outcome was PVR reduction at 16 weeks. M\/T FDC resulted in a significant reduction in PVR at […]<\/p>\n","protected":false},"author":40603,"featured_media":137908,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[878,8],"tags":[877,45,47,185],"ppma_author":[1029],"class_list":{"0":"post-137907","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-acc-2023","8":"category-news","9":"tag-acc-2023","10":"tag-conference","11":"tag-featured","12":"tag-news","13":"author-leah-kosyakovsky"},"authors":[{"term_id":1029,"user_id":40603,"is_guest":0,"slug":"leah-kosyakovsky","display_name":"Leah Kosyakovsky","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/864bde69f6f1f80e91e4a97f0a0ba8daa64c2bb702be09ed787444c7dfa045bb?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137907","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40603"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=137907"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137907\/revisions"}],"predecessor-version":[{"id":137909,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/137907\/revisions\/137909"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/137908"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=137907"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=137907"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=137907"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=137907"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}