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.