Although there have been a wide variety of disease states covered at this year’s CHEST conference, much of the focus has been on those under the umbrella of pulmonary vascular disease, such as pulmonary arterial hypertension and deep vein thrombosis. Here are some of the new study highlights related to pulmonary vascular disease.
One of the most popular sessions featured study data from the late-breaking study by Rubin et al, Effect of Macitentan on Morbidity and Mortality in Pulmonary Arterial Hypertension (PAH): Results From the SERAPHIN Trial.
Many recent oral PAH therapies that have used exercise capacity as the primary endpoint have been approved. In this trial, researchers studied the effect of macitentan, a novel dual endothelin receptor antagonist (ERA) with enhanced tissue penetration, on morbidity and mortality in PAH patients. The research team randomized 742 patients to placebo (n = 250), macitentan 3 mg (n = 250) or macitentan 10 mg (n = 242), with mean treatment duration being 85.3, 99.5, and 103.9 weeks, respectively. The study authors report that “macitentan reduced the risk of occurrence of morbidity and mortality events versus placebo by 30% in the 3-mg group (97.5% confidence interval [CI]: 4%-48%; P
= .0108) and 45% in the 10-mg group (97.5% CI: 24%-61%; P
<.0001),” leading them to conclude that “macitentan demonstrated a significant effect on the combined endpoint of morbidity and mortality, with a favorable safety profile, in the largest and longest randomized controlled trial of therapy in PAH to date.”
Sidharta et al released the information from their study, Single-Dose Pharmacokinetics, Safety, and Tolerability of Macitentan, a New Endothelin Receptor Antagonist, in Subjects with Mild, Moderate, or Severe Hepatic Impairment
, which investigated “the pharmacokinetics (PK), safety, and tolerability of the endothelin receptor antagonist macitentan in subjects with hepatic impairment of varying severity versus healthy subjects.” This open-label, single-center study divided subjects into 4 groups based on hepatic function: mild hepatic impairment; moderate hepatic impairment; severe hepatic impairment; and healthy subjects. All subjects received a single dose of macitentan 10 mg. Length of follow-up varied among the groups, and researchers state that “no effect of hepatic impairment on macitentan PK was concluded when 90% confidence intervals (CI) of geometric mean PK parameter ratios were within reference limits of 0.8 to 1.25.” Upon finishing the study, the research team concluded that “the difference in macitentan PK between healthy and hepatically impaired subjects is not considered clinically relevant,” and added that “macitentan was well tolerated with no new or unexpected safety findings reported.”
Mehta et al presented data from their study, Current Clinical Practices in PAH: Challenges and Opportunities to Improve Care.
Because pulmonary arterial hypertension (PAH) is an under-recognized and inadequately treated form of pulmonary vascular disease, the researchers in this study set out to assess current clinical practices of pulmonologists, cardiologists, and primary care physicians (PCPs) in PAH management to “identify knowledge, competency, and practice gaps and barriers to improving patient care.” After developing an educational needs assessment survey consisting of 25 questions, the study authors received 377 physician responses. Among other findings, the researchers reported that “more than 65% of pulmonologists, 75% of cardiologists, and 85% of PCPs reported that their practices do not have an algorithm for PAH management,” and that “nearly 20% of pulmonologists, 30% of cardiologists, and 40% of PCPs did not recommend right heart catheterization to confirm a diagnosis of PAH.” Upon completion of this study, the researchers concluded that their assessment identified gaps in PAH diagnosis and management, and added that “further assessment of physicians after participating in educational interventions is planned to demonstrate improvement in clinical practice.”