A POPULATION-BASED STUDY OF APPETITE-SUPPRESSANT DRUGS AND THE RISK OF CARDIAC-VALVE REGURGITATION

Background. Recent case reports suggest that a combination of the appe tite suppressants fenfluramine and phentermine is associated with an i ncreased risk of cardiac-valve regurgitation. There are also reports o f valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months. Methods We conducted a population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfl uramine, and 862 who received phentermine to assess the risk of a subs equent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, we identified a group of 9281 obese subjects who had n ot taken appetite suppressants who were matched to the treated subject s for age, sex, and weight. All subjects were free of diagnosed cardio vascular disease at the start of followup. The average duration of fol low-up for all subjects was about four years. Results. There were 11 c ases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were si x cases of aortic regurgitation, two cases of mitral regurgitation, an d three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only p hentermine. The five-year cumulative incidence of idiopathic cardiac-v alve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interva l, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fen fluramine or dexfenfluramine for less than four months (95 percent con fidence interval, 3.6 to 17.8; P = 0.02 for the comparison with subjec ts who had not taken appetite suppressants), and 35.0 per 10,000 subje cts among those who received either of these medications for four or m ore months (95 percent confidence interval, 16.4 to 76.2; P < 0.001). Conclusions. The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of new ly diagnosed cardiac-valve disorders, particularly aortic regurgitatio n. (N Engl J Med 1998;339:719-24.) (C) 1998, Massachusetts Medical Soc iety.