Regression and Progression of Valvulopathy Associated with Fenfluramine and Phentermine

Q: What are the key findings of this study?

Fenfluramine exposure duration significantly increased the risk of mild or greater aortic regurgitation (OR 1.32 per 3-month increment, p<0.0001), with 0.44% of users requiring related valve surgery.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Fenfluramine-associated valvular heart disease / regurgitation (n=5743). Intervention: Fenfluramine and/or dexfenfluramine duration of exposure (per 3-month increment) vs. Shorter duration of fenfluramine exposure. Primary outcome: Mild or greater aortic regurgitation (AR) at baseline (OR 1.32 per 3-month increment, 95% CI 1.24-1.40, p=<0.0001).

Q: What does this research mean for the field?

Duration of fenfluramine exposure significantly increases the risk of mild or greater aortic regurgitation (OR 1.32 per 3-month increment), with a subset of patients requiring related valve surgery. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Charles F. Dahl; Marvin R. Allen

doi:10.7326/0003-4819-136-6-200203190-00018

March 19, 2002Annals of Internal Medicine

Regression and Progression of Valvulopathy Associated with Fenfluramine and Phentermine

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Key result

Longer fenfluramine exposure is linked to ~32% higher aortic regurgitation risk per 3-month increment.

OR 1.32 per 3-month increment
95% CI 1.24-1.40
P<0.0001
n=5,743

Why the study?

The combination of fenfluramine and phentermine was used extensively in the study area, prompting serial echocardiographic evaluation of associated valvulopathy after drug cessation.

Study Design

Type

Cohort (n=5,743)

Blinding

Partially blinded (echocardiogram readers were blinded to fenfluramine use between February 1999 and May 2000)

Multicenter

Yes

PICO

P

Population

5,743 former users of fenfluramine or dexfenfluramine (84% female, ages <20 to ≥70 years) referred for echocardiography in Utah County and followed for up to 6.5 years.

E

Exposure / Comparator

Fenfluramine and/or dexfenfluramine duration of exposure (per 3-month increment) vs Shorter duration of fenfluramine exposure

O

Primary Outcome

Mild or greater aortic regurgitation (AR) at baseline — OR 1.32 per 3-month increment (1.24-1.40), p=<0.0001

Main Result

Odds Ratio: 1.32 (95% CI 1.24–1.4)

p-value: p=<0.0001

Limitations

Retrospective observational design using semi-quantitative rather than quantitative echocardiographic scoring methods
Co-morbidities (hypertension, diabetes, coronary artery disease) and clinical symptoms were not systematically or consistently recorded
Potential selection or referral bias as patients were referred by physicians rather than randomly sampled
No unexposed internal control group
Potential underestimation of valve surgery incidence if patients underwent surgery or follow-up at outside institutions

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Answers are grounded in this paper and cite their sources.

Implication

Supports serial echocardiographic monitoring after fenfluramine exposure; extends duration-dependent risk data from prior observational cohorts.

Abstract

Letters19 March 2002Regression and Progression of Valvulopathy Associated with Fenfluramine and PhentermineCharles F. Dahl, MD and Marvin R. Allen, MDCharles F. Dahl, MDUtah Valley Regional Medical CenterProvo, UT 84604 and Marvin R. Allen, MDUtah Valley Regional Medical CenterProvo, UT 84604Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-136-6-200203190-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read the reports by Mast and colleagues (1) and Weissman and coworkers (2) with interest. Because the combination of fenfluramine and phentermine ("fen-phen") was used extensively in our area, we have asked all patients presenting at our institution for echocardiography in the past 3.5 years about use of these drugs. Data from our registry have been reported elsewhere (3).One hundred twenty patients in our registry had follow-up echocardiography at least twice after cessation of fenfluramine–phentermine use. The mean age of these patients was 49 years, and the mean duration between echocardiograms was 10.6 months. Ninety-nine ...References1. Mast ST, Jollis JG, Ryan T, Anstrom KJ, Crary JL. The progression of fenfluramine-associated valvular heart disease assessed by echocardiography. Ann Intern Med. 2001;134:261-6. [PMID: 11182835] LinkGoogle Scholar2. Weissman NJ, Panza JA, Tighe JF, Gwynne JT. Natural history of valvular regurgitation 1 year after discontinuation of dexfenfluramine therapy. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;134:267-73. [PMID: 11182836] LinkGoogle Scholar3. Dahl CF, Allen MR, Jeffcoats JA. The prevalence of significant valvular regurgitation and pulmonary hypertension in 753 patients who took fenfluramine and phentermine in a community setting [Abstract]. J Am Coll Cardiol. 1999;33:549A. MedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Charles F. Dahl, MD; Marvin R. Allen, MDAffiliations: Utah Valley Regional Medical CenterProvo, UT 84604 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Progression of Fenfluramine-Associated Valvular Heart Disease Assessed by Echocardiography Steven T. Mast , James G. Jollis , Thomas Ryan , Kevin J. Anstrom , and Jack L. Crary Natural History of Valvular Regurgitation 1 Year after Discontinuation of Dexfenfluramine Therapy Neil J. Weissman , Julio A. Panza , John F. Tighe Jr. , and John T. Gwynne Metrics Cited byDrug-Induced Fibrosing LesionsFenfluraminesAdverse effects of benfluorex on heart valves and pulmonary circulationIncreased Risk of Left Heart Valve Regurgitation Associated With Benfluorex Use in Patients With Diabetes MellitusBenfluorex (Mediator®) et atteintes valvulairesHow can benfluorex-related heart valve disease be identified by echocardiography?Pharmacologic Therapies for ObesityADVERSE CARDIOVASCULAR EFFECTS OF NON-CARDIOVASCULAR DRUGSThe Burden of Valvular Heart DiseaseValvular regurgitation and surgery associated with fenfluramine use: an analysis of 5743 individualsFenfluraminesSafety of Drug Therapies Used for Weight Loss and Treatment of ObesityCentral nervous system stimulants and drugs that suppress appetite 19 March 2002Volume 136, Issue 6Page: 489KeywordsDrugsEchocardiographyFood and Drug AdministrationMitral insufficiency ePublished: 19 March 2002 Issue Published: 19 March 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

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Cite This Study

Dahl et al. (2002) conducted a cohort in Fenfluramine-associated valvular heart disease / regurgitation (n=5,743). Fenfluramine and/or dexfenfluramine duration of exposure (per 3-month increment) vs. Shorter duration of fenfluramine exposure was evaluated on Mild or greater aortic regurgitation (AR) at baseline (OR 1.32 per 3-month increment, 95% CI 1.24-1.40, p=<0.0001). Fenfluramine exposure duration significantly increased the risk of mild or greater aortic regurgitation (OR 1.32 per 3-month increment, p<0.0001), with 0.44% of users requiring related valve surgery.

synapsesocial.com/papers/6ad9ca455d9e224b442268f1 https://doi.org/10.7326/0003-4819-136-6-200203190-00018

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Regression and Progression of Valvulopathy Associated with Fenfluramine and Phentermine

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Regression and Progression of Valvulopathy Associated with Fenfluramine and Phentermine

Study Design

PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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