Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group

N Engl J Med. 1996 Aug 29;335(9):609-16. doi: 10.1056/NEJM199608293350901.


Background: Recently, a cluster of patients was observed in France in whom primary pulmonary hypertension developed in patients exposed to derivatives of fenfluramine in appetite suppressants (anorexic agents), which are used for weight control. We investigated the potential role of anorexic agents and other suspected risk factors for primary pulmonary hypertension.

Methods: In a case-control study, we assessed 95 patients with primary pulmonary hypertension from 35 centers in France, Belgium, the United Kingdom, and the Netherlands and 355 controls recruited from general practices and matched to the patients' sex and age.

Results: The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension (odds ratio with any anorexic-drug use, 6.3; 95 percent confidence interval, 3.0 to 13.2). For the use of anorexic agents in the preceding year, the odds ratio was 10.1 (95 percent confidence interval, 3.4 to 29.9). When anorexic drugs were used to a total of more than three months, the odds ratio was 23.1 (95 percent confidence interval, 6.9 to 77.7). We also confirmed an association with several previously identified risk factors: a family history of pulmonary hypertension, infection with the human immunodeficiency virus, cirrhosis, and use of cocaine or intravenous drugs.

Conclusions: The use of anorexic drugs was associated with the development of primary pulmonary hypertension. Active surveillance for this disease should be considered, particularly since their use is expected to increase in the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Appetite Depressants / adverse effects*
  • Belgium / epidemiology
  • Case-Control Studies
  • Female
  • Fenfluramine / adverse effects*
  • France / epidemiology
  • Heart Function Tests
  • Hemodynamics
  • Humans
  • Hypertension, Pulmonary / chemically induced*
  • Hypertension, Pulmonary / epidemiology
  • Hypertension, Pulmonary / physiopathology
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Prospective Studies
  • Respiratory Function Tests
  • Risk Factors
  • United Kingdom / epidemiology


  • Appetite Depressants
  • Fenfluramine