Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials.

Abstract

BACKGROUND:

Lorcaserin is a selective 5-HT2C agonist evaluated for weight management in clinical trials. Echocardiographic monitoring was conducted to test the hypothesis that selective 5-HT2C agonism would avoid valvular heart disease.

METHODS AND RESULTS:

Echocardiographic and weight change data from 5249 obese and overweight patients in 3 phase 3 trials were integrated. Treatment duration with 10 mg lorcaserin twice daily or placebo was 52 weeks. The proportions of patients who developed Food and Drug Administration-defined valvulopathy (≥ mild aortic or ≥ moderate mitral regurgitation) and changes in regurgitant grade at each heart valve were evaluated. Possible associations between weight or body mass index change and valvulopathy were explored. New valvulopathy was present in 2.04% of placebo and 2.37% of lorcaserin recipients at 52 weeks (risk difference, 0.33%; 95% confidence interval, -0.46 to 1.13; risk ratio, 1.16 [all patients with sufficient echocardiographic data, last-observation-carried-forward imputation] or 1.03 [patients who completed 52 weeks]). Changes in weight and body mass index were negatively associated with presence of valvulopathy at week 52 (P=0.02 and P=0.04, respectively); a 5% decrease in weight was associated with an odds ratio of 1.15 for Food and Drug Administration-defined valvulopathy. Most changes in regurgitation were ±1 grade in both treatment groups at all heart valves.

CONCLUSIONS:

In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo. Point estimates for risk ratios ranged from 1.03 to 1.16 and may be at least partially influenced by greater weight loss in the lorcaserin group than in the placebo group.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00395135, NCT00603291, NCT00603902.

• Authors: Neil J Weissman, Matilde Sanchez, Gary G Koch, Steven R Smith, William R Shanahan, Christen M Anderson
• Journal: Circulation. Cardiovascular imaging (Circ Cardiovasc Imaging) Vol. 6 Issue 4 Pg. 560-7 (Jul 2013) ISSN: 1942-0080 [Electronic] United States
• PMID: 23661689 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Obesity Agents
• Benzazepines
• Receptor, Serotonin, 5-HT2C
• Serotonin 5-HT2 Receptor Agonists
• lorcaserin

Topics

• Adolescent
• Adult
• Aged
• Anti-Obesity Agents (adverse effects, therapeutic use)
• Aortic Valve Insufficiency (diagnostic imaging, etiology, metabolism, prevention & control)
• Benzazepines (adverse effects, therapeutic use)
• Body Mass Index
• Female
• Humans
• Male
• Middle Aged
• Mitral Valve Insufficiency (diagnostic imaging, etiology, metabolism, prevention & control)
• Obesity (complications, diagnosis, drug therapy, metabolism)
• Odds Ratio
• Prospective Studies
• Receptor, Serotonin, 5-HT2C (drug effects, metabolism)
• Risk Factors
• Serotonin 5-HT2 Receptor Agonists (adverse effects, therapeutic use)
• Severity of Illness Index
• Time Factors
• Treatment Outcome
• Ultrasonography
• Weight Loss (drug effects)
• Young Adult