PURPOSE: Serotonin signaling, via its receptors and transporter, may contribute to the pathogenesis of pulmonary arterial hypertension (PAH). A recent analysis of registry data from a single center found that selective serotonin reuptake inhibitor (SSRI) use was associated with improved PAH outcomes. The present study explored the associations between use of SSRIs and PAH outcomes using the large, multicenter, US-based Registry to EValuate Early and Long term PAH disease management (REVEAL) database.
METHODS: All subjects were adults (age >18 years) and had Group 1 PAH meeting specific hemodynamic criteria. Subjects were classified as non-SSRI, high affinity (HA)-SSRI, and other SSRI users. Four outcome variables were compared: survival, freedom from 15% reduction in six minute walk distance (6MWD), freedom from worsened New York Heart Association functional class (NYHA-FC), and a composite endpoint including all three. Multivariable Cox models were used for outcome measures.
RESULTS: 3300 patients were included in this study: non-SSRI, n=2678, HA-SSRI, n=363, and other SSRI, n=259. The distribution of Group 1 PAH subtypes was similar across study groups. HA-SSRI users were more likely female, Caucasian, and older than non-SSRI users (all P<0.05). At enrollment, HA-SSRI users had lower 6MWD and higher proportions of NYHA-FC III or IV compared with non-SSRI users (both P<0.05). There was no difference in adjusted survival (HR, 1.04; 95% CI, 0.83-1.31; P=0.71), freedom from 15% reduction in 6MWD, freedom from worsened NYHA-FC, or the composite endpoint (HR, 1.01; 95% CI, 0.86-1.18; P=0.91) between HA-SSRI users and non-SSRI users. Similar negative results were found between the non-SSRI and other SSRI users.
CONCLUSION: In this large contemporary population study of PAH, SSRI use was not associated with improved functional or survival outcomes, despite the observation that SSRI users had worse functional disability at the time of their presentation.
CLINICAL IMPLICATIONS: These data contradict evidence predating the modern treatment era favoring use of SSRIs and therefore do not support the use of SSRIs as adjunctive therapy in PAH.
DISCLOSURE: Ali Sadoughi, Grant monies (from sources other than industry) Kari Roberts NIH K23 HL089812-01A1 (2008-2013). N. Hill received research grants from NIH.; Grant monies (from industry related sources) N. Hill received research grants Actelion, Bayer, Genzyme, Gilead, Pfizer, United Therapeutics. H Farber received Grant Support from Gilead.; Employee Ginny P. Lai is an employee of ICON Clinical Research, which was paid by Actelion to provide biostatistical and analytical services for this research. ICON is also paid by other pharmaceutical, biotechnology, and medical device companies to provide clinical research and analytical services.; Consultant fee, speaker bureau, advisory committee, etc. Kari Roberts is a member of Gilead Advisory Board. Harrison W. Farber serves as a consultant and is on the speaker’ s bureau for Actelion. Dr. Farber has received honoraria for his service on the REVEAL Steering Committee, which is supported by Actelion. He also serves a a consultant for Gilead. D. McCollister participated in Advisory Boards for Gilead and Actelion.; No Product/Research Disclosure Information