Anorexigens and Pulmonary Hypertension in the United States

Stuart Rich, MD, FCCP; Lewis Rubin, MD, FCCP; Alexander M. Walker, MD, DrPH; Sebastian Schneeweiss, MD and Lucien Abenhaim, MD From the Section of Cardiology (Dr. Rich), Rush Medical College, Chicago, IL; the Section of Pulmonary and Critical Care Medicine (Dr. Rubin), University of California San Diego, School of Medicine, San Diego, CA; the Department of Epidemiology (Drs. Walker and Schneeweiss), Harvard School of Public Health, Cambridge, MA; and the Department of Epidemiology and Biostatistics (Dr. Abenhaim), Jewish General Hospital, McGill University, Montreal, Canada.


CHEST. 2000;117(3) 

In This Article

Materials and Methods

SNAP was a prospective surveillance study that collected information on patients diagnosed with pulmonary hypertension in 12 centers in North America (see "Appendix"). The sites were selected based on the principal investigator's prior activity in the National Institutes of Health Registry of Primary Pulmonary Hypertension,[11] as well as their participation in recent clinical trials for the therapy of pulmonary hypertension.

Every patient who presented to these medical centers with a diagnosis of pulmonary hypertension that was confirmed was eligible for the study. The pulmonary hypertension was characterized by the investigator as primary or associated with another condition. Patient enrollment began on September 1, 1996, and ended on December 31, 1997. Each center had local institutional review board approval.

Pulmonary hypertension was defined as a mean pulmonary artery pressure, measured at cardiac catheterization, that was > 25 mm Hg or as a pulmonary artery systolic pressure, estimated by echocardiography or measured at catheterization, that was > 35 mm Hg. Patients were classified as having SPH if they had precapillary pulmonary hypertension and the coexistence of COPD, sleep apnea, pulmonary embolism, interstitial lung disease, liver disease, congenital heart disease or connective tissue disease, all of which were operationally defined for the study. Patients with pulmonary hypertension associated with the HIV were categorized separately. Patients with pulmonary hypertension that was not secondary and was not associated with HIV were categorized as PPH. Patients with evidence of left heart myocardial or valvular heart disease were excluded.

Patients were interviewed with respect to risk factors and drug exposure that were possibly related to their pulmonary hypertension, with special attention paid to the use of antidepressants, anorexigens, and amphetamines. Using standardized forms, study coordinators who had participated in a common training session recorded the patient's drug exposure in the 10 years preceding presentation, noting the date of onset, the date last used, and the cumulative months of use. For the most part, interviews took place before the final diagnosis had been established.

Drug use was classified according to chemical class. The fenfluramine appetite suppressants (dexfenfluramine and fenfluramine racemate) were gathered together for analytic purposes, as were amphetamines, and antidepressants. Phentermine was kept as a distinct entity in the analysis. A class of "other anorexigens" included phendimetrazine, mazindol, diethylpropion, and oral phenylpropanolamine preparations. Nonprescription medications for conditions other than weight loss were not categorized or analyzed. The duration of use and the interval prior to the onset of symptoms were examined only in very broad categories (< 6 months vs >= 6 months) to account for anticipated errors in patient recall.

Associations between drug use and PPH vs SPH were explored through logistic regression, with adjustment for age, gender, body mass index (BMI), date of the onset of symptoms, and study center. Cases with missing data for any covariate were omitted from the regression analysis.