Primary Pulmonary Hypertension Associated With the Use of Fenfluramine Derivatives

¹ From the Center for Pulmonary Vascular Disease, Paris-Sud University, Clamart, France
² From the Center for Pulmonary Vascular Disease, Paris-Sud University, and Marie Lannelongue Hospital, Clamart, France

Gérald Simonneau, MD, Service de Pneumologie, Hôpital Antoine Béclére, 157 rue de la Porte de Trivaux, 92140 Clamart, France

Fenfluramine derivatives (Fds) are a well-established risk factor for primary pulmonary hypertension (PPH). We compared 62 Fd-PPH patients (61 women) evaluated in our center between 1986 and 1997 with 125 sex-matched PPH patients nonexposed to Fd referred during the same period (control PPH). In the Fd-PPH group, 33 patients (53%) used dexfenfluramine alone, 7 patients (11%) used fenfluramine alone, and 5 patients (8%) used both drugs. In 17 cases (27%), Fd use was associated with that of amphetamines. Most of the exposed patients used Fd for at least 3 months (81%). The interval between the onset of dyspnea and that of drug intake was 49±68 months (27 days to 23 years). At the time of diagnosis, Fd-PPH and control PPH were similar in terms of New York Heart Association functional class and symptoms. The two groups significantly differed only in terms of age (50±12 vs 40±14 years) and body mass index (28±6 vs 23±4). The two groups displayed similar severe baseline hemodynamics (total pulmonary vascular resistance: 32±12 vs 31±12 IU/m²), but the percentage of responders to acute vasodilator testing was higher in control PPH (27% vs 10%, p<0.01). As a result, more patients were treated with oral vasodilators in the control PPH group (36% vs 16%, p<0.01) and long-term epoprostenol infusion was more frequently used in the Fd-PPH group (52% vs 31%, p<0.01). Overall survival was similar in the two groups with a 3-year survival rate of 50%.