Phentermine

Cardiovascular

In a systematic review of 1279 patients taking fenfluramine, dexfenfluramine, or phentermine, evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) had aortic and mitral regurgitation respectively [ ]. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% CI = 1.79, 3.01) and an attributable rate of 4.9% and, for mitral regurgitation, a relative risk ratio of 1.55 (95% CI = 1.06, 2.25) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. The authors concluded that the risk of valvular heart disease is significantly increased by the appetite suppressants. Nevertheless, valvulopathy is much less common than suggested by previous less methodologically rigorous studies.

Spontaneous rupture of a retroperitoneal aneurysm occurred in a 70-year-old woman who had been taking phentermine hydrochloride, 30 mg/day, for about 1 month [ ]. Other long-term medications included fluoxetine and amitriptyline, and she had no history of coronary artery disease, hypertension, diabetes, or complications of pregnancy. Although it is plausible that phentermine could have contributed to the ruptured aneurysm, other possibilities should be considered, particularly rupture of an anomalous retroperitoneal blood vessel.

Fatal pulmonary hypertension occurred in a 32-year-old man who had been taking phentermine in unknown doses for 4 months [ ].

Combined use of fenfluramine and phentermine (“Fen-Phen”) has been associated with varying degrees of valvular regurgitation and pulmonary hypertension. In 57 men and women (30 taking Fen-Phen and 27 controls matched for BMI) chamber dimensions, wall motion, diastolic function, valvular abnormalities, left ventricular ejection fraction, and pulmonary artery pressures were measured [ ]. Those taking Fen-Phen were studied shortly after they stopped taking it and again 6–12 months later. The results in these subjects were then compared with the findings in 660 randomly selected cardiac patients with heart disease that was not caused by Fen-Phen. Valvular regurgitation was greatest among patients who had recently stopped taking Fen-Phen, 57% of all valves having regurgitation, 88% of which were “mild”; they also had the largest left ventricles at end diastole (5.03 cm) and systole and higher pulmonary artery pressures (29 mmHg), associated with a lower incidence (14%) of pulmonic regurgitation. The number of people with aortic regurgitation fell with time after the withdrawal of Fen-Phen. However, among those who continued to have aortic regurgitation, there was an increase in the number of those who progressed from mild to moderate regurgitation, with an associated increase in left ventricular end-diastolic and end-systolic dimensions and left ventricular ejection fraction. There was an increase in the incidence of pulmonic regurgitation with time and a fall in pulmonary artery pressure from 29 to 14 mmHg. The incidence of tricuspid and mitral regurgitation fell with time, while pulmonic and aortic regurgitation tended to increase or become more severe when present. Dilatation of the pulmonary ring, resulting from raised pulmonic pressures, with subsequent pulmonary regurgitation and reduced pulmonary artery pressures, appears to be a functional change in the hearts of these individuals with unknown long-term consequences.