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Original Research: Pulmonary Vascular Disease |

Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Pulmonary Arterial HypertensionSerotonin Uptake and Pulmonary Hypertension

Ali Sadoughi, MD; Kari E. Roberts, MD; Ioana R. Preston, MD, FCCP; Ginny P. Lai, MPH; Deborah H. McCollister, RN, BSN; Harrison W. Farber, MD, FCCP; Nicholas S. Hill, MD, FCCP
Author and Funding Information

From the Department of Medicine (Dr Sadoughi), Hofstra-North Shore LIJ School of Medicine, New Hyde Park, NY; the Department of Medicine (Drs Roberts, Preston, and Hill), Tufts Medical Center, Boston, MA; ICON Late Phase & Outcomes Research (Ms Lai), San Francisco, CA; the University of Colorado Denver (Ms McCollister), Denver, CO; and the Department of Medicine (Dr Farber), Boston University School of Medicine, Boston, MA.

Correspondence to: Nicholas S. Hill, MD, FCCP, Tufts Medical Center, Department of Medicine, Pulmonary, Critical Care and Sleep Division, 800 Washington St, Mailbox 257, Boston, MA 02111; e-mail: nhill@tuftsmedicalcenter.org


Drs Sadoughi and Roberts contributed equally to the preparation of the manuscript.

Funding/Support: Funding and support for the REVEAL Registry was provided by CoTherix, Inc, and its affiliate Actelion Pharmaceuticals US, Inc. Medical writing support was provided by Scarlett Geunes-Boyer, PhD, of inScience Communications, Springer Science+Business Media, and funding was provided by Actelion Pharmaceuticals US, Inc.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(2):531-541. doi:10.1378/chest.12-2081
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Background:  Selective serotonin reuptake inhibitors (SSRIs) have been suggested to offer therapeutic benefit in patients with pulmonary arterial hypertension (PAH). We conducted two analyses to explore the association between SSRI use and PAH outcomes using the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry).

Methods:  First, new users (SSRI-naive patients who initiated treatment after enrollment, incident use analysis, n = 220) were matched (1:2) with non-SSRI users (nonusers, n = 440) by enrollment center, sex, date of most recent visit, age, and 6-min walk distance. Second, a cross-sectional design was used to compare nonusers (n = 2,463), high-affinity SSRI users (n = 430), and non-high-affinity SSRI users (n = 125) at enrollment. Mortality and a composite end point defined by events indicative of clinical worsening were evaluated.

Results:  New users had a higher risk of death (unadjusted hazard ratio [HR], 1.74; 95% CI, 1.19-2.54; P = .004) and were less likely to be free from the composite end point 2 years after enrollment vs nonusers (25.7% vs 43.2%, respectively; P < .001). Similarly, among prevalent SSRI users (patients with a history of SSRI use at enrollment), high-affinity SSRI users were less likely to be free from the composite end point vs nonusers (unadjusted HR, 1.20; 95% CI, 1.07-1.36; P = .003). In both analyses, differences in outcome were maintained after adjustment for clinical variables previously associated with PAH outcomes.

Conclusions:  In a large population of patients with PAH, incident SSRI use was associated with increased mortality and a greater risk of clinical worsening, although we could not adjust for all potential confounders.

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