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Appetite suppressants and valvular heart disease - a systematic review
Yoon K Loke1, Sheena Derry, Angharad Pritchard-Copley
1Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, OX2 6HE, United Kingdom. yoon.loke@clinpharm.ox.ac.uk
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.
Insights
Appetite suppressants significantly increase the risk of valvular heart disease, including aortic and mitral regurgitation. However, the actual incidence is lower than previously estimated, with rigorous studies showing a much-reduced risk.
Area of Science:
- Cardiology
- Pharmacology
- Public Health
Background:
- Appetite suppressants have been linked to valvular heart disease, but the precise risk remains unclear.
- Initial studies indicated a high prevalence (up to 1 in 3), prompting further investigation.
- This systematic review aims to clarify the risk of valvular heart disease associated with appetite suppressant use.
Purpose of the Study:
- To systematically assess the risk of valvular heart disease in patients using appetite suppressants.
- To evaluate the association between specific appetite suppressants (fenfluramine, dexfenfluramine, phentermine) and valvular heart disease.
- To compare risk estimates from different study designs.
Main Methods:
- Systematic review of controlled and uncontrolled observational studies, and randomized controlled trials.
- Inclusion of studies on obese patients treated with fenfluramine, dexfenfluramine, or phentermine.
- Outcomes assessed: mild or greater aortic regurgitation, moderate or greater mitral regurgitation via echocardiography.
Main Results:
- In uncontrolled cohort studies (n=1279), 18% had aortic regurgitation and 5% had mitral regurgitation.
- Controlled cohort studies showed increased risks: relative risk ratio (RRR) for aortic regurgitation was 2.32 (95% CI 1.79-3.01) with 4.9% attributable rate.
- Controlled cohort studies showed RRR for mitral regurgitation was 1.55 (95% CI 1.06-2.25) with 1.0% attributable rate; one unrelated case in RCTs.
Conclusions:
- Appetite suppressants reviewed significantly elevate the risk of valvular heart disease.
- Valvulopathy is less common than initially suggested by less rigorous studies.
- The findings underscore the importance of considering drug-specific risks in clinical practice.