Chest
Volume 136, Issue 3, September 2009, Pages 694-700
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Original Research
Pulmonary Hypertension
Selective Serotonin Reuptake Inhibitors and the Incidence and Outcome of Pulmonary Hypertension

https://doi.org/10.1378/chest.08-2823Get rights and content

Background

Selective serotonin reuptake inhibitors (SSRIs) prevent the development of and reverse pulmonary hypertension (PH) in animal models. We sought to determine whether SSRIs are associated with a decreased incidence of PH in at-risk patients and whether SSRIs are associated with decreased mortality in patients with established PH.

Methods

In a case-control study of patients enrolled in the Surveillance of Pulmonary Hypertension in America (SOPHIA) registry, we tested whether patients without PH (no-PH group; n = 155) were more likely to be receiving SSRIs when compared to those with confirmed PH (n = 1,180). In a separate cohort study of adults with documented PH in the referral-based Pulmonary Hypertension Connection (PHC) registry (n = 542), we classified patients into categories by SSRI use, and we examined whether SSRI use was associated with decreased mortality.

Results

In SOPHIA, the confirmed PH group was less likely to be receiving SSRIs compared with the no-PH group (univariate odds ratio [OR], 0.56 [95% confidence interval (CI), 0.39 to 0.82]; p = 0.003; multivariate OR, 0.71l [95% CI, 0.48 to 1.06]; p = 0.09). In the PHC, 69 of 542 patients (13%) were receiving SSRIs at the time of referral. During a mean (± SD) follow-up period of 4.0 ± 3.1 years, 12% of patients receiving SSRIs vs 23% of patients not receiving SSRIs died (hazard ratio [HR], 0.35; 95% CI, 0.14 to 0.87; p = 0.023). The association between SSRI use and decreased mortality persisted after adjusting for age, gender, etiology of PH, and obesity (HR, 0.35; 95% CI, 0.14 to 0.88; p = 0.026).

Conclusions

SSRIs appear to be associated with a decreased development of PH and a decreased mortality in PH. These findings provide a rationale for clinical trials of SSRIs in PH.

Section snippets

SOPHIA Registry

The SOPHIA registry (n = 1,335) has been described in detail previously.19 Briefly, the study consisted of a network of 13 PH centers with the aim of determining whether anorexigen use in the United States was associated with an identifiable increase in the incidence of PH. All patients who were referred to specialists at these 13 centers with suspected PH from 1998 to 2001 were enrolled in the SOPHIA registry if they had undergone a thorough evaluation, including cardiac catheterization.20 PH

SOPHIA Registry

Table 1 shows the demographic and clinical features of patients in the confirmed-PH and no-PH groups in the SOPHIA registry, and the difference in SSRI use between these groups. Patients with confirmed PH were less likely to be receiving SSRIs compared to those patients who did not to have PH (p = 0.003). After multivariable adjustment, patients in the confirmed-PH group still had a decreased OR of SSRI use compared with those in the no-PH group, although this finding did not meet statistical

Discussion

We have shown that SSRI use is associated with a decreased incidence of PH and decreased mortality in PH patients by using two large cohorts of patients, the SOPHIA registry and the PHC registry. In support of the beneficial effects of SSRIs in humans, we demonstrated a reduced incidence of PH in patients with risk factors (eg, connective tissue diseases and anorexigens) for PH and an improved survival time in patients with newly diagnosed PH. Our finding that increasing affinity of SSRIs for

Conclusions

In summary, we found that patients with PH associated with several types of risk factors were less likely to be receiving SSRIs compared with patients who were found not to have PH. We also found that in patients with established PH, SSRI use was independently associated with decreased mortality. The consistency of our findings in the two cohorts we studied, coupled with compelling animal data and data from other observational studies,18, 29 point to SSRIs as potential therapies for the

Acknowledgments

Author contributions: Drs. Shah, Gomberg-Maitland, and Rich conceived and designed the study. Dr. Shah performed the statistical analyses and drafted the article. Drs. Gomberg-Maitland, Thenappan, and Rich acquired the study data. All authors participated in interpreting the data and revising the manuscript for important intellectual content. All authors approved the final version of the manuscript.

Financial/nonfinancial disclosures: Dr. Gomberg-Maitland has received research grant support from

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Funding/Support: Dr. Shah is supported by an Actelion Entelligence Young Investigator Award and an American Heart Association Scientist Development Grant. Dr. Gomberg-Maitland is supported by a Doris Duke Clinical Scientist Development Award.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

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