The Prevalence of Cardiac Valvular Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetite-Suppressant Drugs

Khan, Mehmood; Herzog, Charles A.; Peter, John; Hartley, Guilford G.; Madlon-Kay, Richard; Dick, Candace D.; Asinger, Richard W.; Vessey, John T.

doi:10.1056/nejm199809103391101

Cited by 244 publications

(82 citation statements)

References 27 publications

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“…It is important to note that following the suspension of fenfluramine and dexfenfluramine because of a potential association with disturbances in cardiac valvular function (Khan et al, 1998;Weissman et al, 1998), all subjects (including placebos) were subjected to an echocardiogram. Following this assessment, a detailed evaluation of cardiac valvular function was performed by cardiologists who detected no abnormalities in response to the use of fenfluramine under these conditions (Prud'homme et al, 1999).…”

Section: Methodsmentioning

confidence: 99%

Reduction of visceral adipose tissue during weight loss

et al. 2002

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Objective: The aims of the present study were to retrospectively: (1) compare how weight loss affects the reduction of adipose tissue from three different sites between men and women; and (2) to verify whether gender differences in the reduction of adipose tissue are influenced by changes in fat mass (FM) and initial levels of fat in different compartments. Design: Double-blind randomized treatment with fenfluramine once daily coupled to a non-macronutrient specific energy restriction. Subjects: Seventeen obese men (age 43.9 AE 1.5 and body mass index (BMI) 34.3 AE 0.7) and 17 obese women (age 41.2 AE 1.2 and BMI 35.7 AE 0.6). Interventions: Subjects were given fenfluramine (60 mg) or placebo once daily and were also subjected to a non-macronurient specific energy restriction of 72.9 MJ=day (7700 kcal=day) for 15 weeks. Results: Body weight, FM, fat-free mass (FFM), waist circumference, BMI, as well as visceral (VAT), subcutaneous abdominal (SAT) and thigh (TAT) adipose tissue were all significantly reduced. Men lost significantly more VAT (741.6%) than SAT (722.5%), or than TAT (720.5%) while no site difference in fat loss was observed in women when changes were calculated as a percentage of initial levels. Men lost about twice as much fat from the VAT compartment than did women (P < 0.05), even after having considered changes in FM as a potential covariate. In absolute values, TAT was reduced to a lesser extent in men than in women. However, when initial levels of respective fat depots were also taken into account, gender differences in VAT and TAT loss were no longer statistically significant. Conclusion: These results suggest that gender differences in VAT reduction during weight loss are independent of changes in FM. However, once initial levels of VAT are also taken into account, gender differences in the reduction of this tissue during weight loss are no longer apparent.

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Section: Methodsmentioning

confidence: 99%

Reduction of visceral adipose tissue during weight loss

et al. 2002

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“…The longterm safety of antiobesity medications is also a concern given previous evidence linking fenfluramine and dexfenfluramine to valvular heart disease and pulmonary hypertension, and recent concerns regarding sibutramine and increased cardiovascular risk. [24][25][26][27][28] Given the rising prevalence of obesity and the potential for more widespread use of antiobesity drugs, we sought to review the available evidence regarding the long-term efficacy and safety of such agents.…”

Section: Introductionmentioning

confidence: 99%

Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials

2003

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CONTEXT: Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens. OBJECTIVE: To review systematically the long-term efficacy and safety of approved antiobesity medications. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed. STUDY SELECTION: Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion. DATA EXTRACTION: Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms. RESULTS: A total of 11orlistat (n ¼ 6021) and three sibutramine (n ¼ 929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3-3.1 kg) or 2.9% (95% CI: 2.3-3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6-4.9 kg) or 4.6% (95% CI: 3.8-5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8-16%) higher with orlistat and 15% (95% CI: 4-27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate. CONCLUSION: There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigourous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

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“…Despite the extensive use of fluoxetine for long-term treatment of depression, there have been no reports of cardiac valve lesions similar to those seen with fenfluramine and dexfenfluramine. 4,6,[20][21][22][23][24][25][26][27][28][29][30][31][32][33] Rothman et al 51 suggested that serotonergic drugs that bind to 5-HT (2B) receptors were associated with cardiac valve lesions. Fenfluramine and dexfenfluramine were among those that bound to 5-HT (2B) receptors, but fluoxetine did not.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9] Weight losses at 1 year were approximately 15-17% of initial body weight with phen-fen [3][4][5][6][7][8][9] compared to losses of 6-10% of initial body weight with single-drug treatment using fenfluramine. [10][11][12][13][14][15][16][17][18][19] When fenfluramine and dexfenfluramine were removed from the market in September 1997 because of concerns about cardiac valve lesions, 4,6,[20][21][22][23][24][25][26][27][28][29][30][31][32][33] some physicians turned to combinations of phentermine and other serotonin-active drugs such as fluoxetine and sertraline in an attempt to reproduce the phen-fen effect. However, there are very few studies published on the efficacy of these combinations for obesity, and none have compared results with phen-fen.…”

Section: Introductionmentioning

confidence: 99%

Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status

et al. 2006

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Background: Obesity treatment with single drugs produces weight losses of about 8-10% of initial body weight. Few studies of combinations of drugs for treating obesity have been published. The combination of phentermine, an adrenergic agent, and fenfluramine, a serotonergic agent, (phen-fen) produced weight losses of about 15% of initial body weight. Fenfluramine is no longer available because it was associated with cardiac valve lesions. Phentermine-fluoxetine (phen-flu) has been proposed as an alternative for phen-fen. Objective: To compare the efficacy of treatment and prevalence of cardiac valve abnormalities on phen-flu vs phen-fen. Design: Retrospective chart review of all patients treated for at least 3 months with phen-flu (N ¼ 97) to a random sample of patients treated with phen-fen (N ¼ 98) in the Clinical Nutrition Clinic at the University of Wisconsin. Comparison of echocardiograms in all patients treated solely with phen-flu (N ¼ 21) to a random sample of patients treated with phen-fen (N ¼ 47), and to a group of subjects never treated with obesity drugs (N ¼ 26). Results: With last observation carried forward analysis (LOCF), at 6 months of treatment the phen-fen patients lost 12.670.6% of baseline weight and phen-flu patients lost 9.070.6% (Po0.001). With completers analysis, there were no significant differences in weight loss as a percent of baseline weight at 6 months (14.470.6 vs 13.370.9%). LOCF decreases in body mass index (BMI) at 6 months were À5.3 and À3.6 kg/m 2 for phen-fen and phen-flu, respectively (Po0.001), and 6.270.3 vs 5.470.4 kg/m 2 , respectively, for the completers analysis (P -NS). Dropout rate at 6 months was higher in phen-flu subjects (44 vs 28%). In subjects without atherosclerosis of valves (presumably pre-existing), cardiac valve lesions occurred in eight of 38 phen-fen subjects and in none of 15 phen-flu subjects or 25 control subjects who had not been treated with drugs. Conclusions: The combination of phentermine and fluoxetine was not as effective as phen-fen, but was not associated with cardiac valve lesions. Longer term, larger scale studies of phen-flu are warranted.

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The Prevalence of Cardiac Valvular Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetite-Suppressant Drugs

Abstract: Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.

Cited by 244 publications

References 27 publications

Reduction of visceral adipose tissue during weight loss

Reduction of visceral adipose tissue during weight loss

Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials

Comparison of combinations of drugs for treatment of obesity: body weight and echocardiographic status

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