Appetite suppressants and valvular heart disease - a systematic review.
BACKGROUND
Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants.


METHODS
We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity.


RESULTS
Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) 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.


CONCLUSIONS
The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies.
Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, OX2 6HE, United Kingdom. yoon.loke@clinpharm.ox.ac.uk
Yoon K
YK
Loke
Sheena
S
Derry
Angharad
A
Pritchard-Copley
D001067:Appetite Depressants / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D020372:Dexfenfluramine / Q000009:adverse effects; D005277:Fenfluramine / Q000009:adverse effects; D006349:Heart Valve Diseases / Q000139:chemically induced*; D006801:Humans; D010645:Phentermine / Q000009:adverse effects
D001067:Appetite Depressants; D005277:Fenfluramine; D010645:Phentermine; D020372:Dexfenfluramine