Temporal trends and drug exposures in pulmonary hypertension: An American experience

Background: Reports have linked anorexigen intake to an increased risk of pulmonary arterial hypertension (PAH). With the rise in anorexigen use in the latter half of the last decade, we established a surveillance network within the United States to monitor temporal trends in the number of reported cases of PAH. We also studied whether use of anorexigens and other drugs differed among patients with pulmonary hypertension of different etiologies. Methods: Newly diagnosed subjects (N = 1335) at 13 tertiary pulmonary hypertension centers were enrolled between January 1998 and June 2001. Patient-reported medication use was obtained by a telephone interview. Patients were classified as to the type of pulmonary hypertension. Poisson regression models were fitted to monthly case counts, and logistic regression methods were used to assess the association between type of pulmonary hypertension and medication use. Results: The average monthly number of reported cases of PAH and other categories of pulmonary hypertension did not change over the study period. Fenfluramine or dexfenfluramine use during the 5 years before the time of the interview was preferentially associated with PAH. Fenfluramine/dexfenfluramine use was particularly common in cases referred but found not to have pulmonary hypertension. Conclusions: No epidemic of anorexigen-related PAH was evident during the study period. As persons who had taken fenfluramine or dexfenfluramine were particularly likely to be referred for evaluation of pulmonary hypertension, it is unlikely that the failure to detect an anorexigen-induced rise in primary pulmonary hypertension was because of underascertainment. The association between fenfluramine derivatives and PAH is consistent with the risk elevations previously reported.