Cardiovascular safety of lorcaserin in overweight or obese patients

E. A. Bohula, S. D. Wiviott, D. K. McGuire, S. E. Inzucchi, J. Kuder, K. A. Im, Christina Fanola, A. Qamar, C. Brown, A. Budaj, A. Garcia-Castillo, M. Gupta, L. A. Leiter, N. J. Weissman, H. D. White, T. Patel, B. Francis, W. Miao, C. Perdomo, S. DhaddaM. P. Bonaca, C. T. Ruff, A. C. Keech, S. R. Smith, M. S. Sabatine, B. M. Scirica

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

BACKGROUND Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P = 0.04). CONCLUSIONS In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo.

Original languageEnglish (US)
Pages (from-to)1107-1117
Number of pages11
JournalNew England Journal of Medicine
Volume379
Issue number12
DOIs
StatePublished - Sep 20 2018

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Safety
Placebos
Confidence Intervals
Weight Loss
Receptor, Serotonin, 5-HT2C
Serotonin Receptor Agonists
lorcaserin
Unstable Angina
Anniversaries and Special Events
Appetite
Hypoglycemia
Hospitalization
Cardiovascular Diseases
Heart Failure
Heart Rate
Stroke
Odds Ratio
Myocardial Infarction
Blood Pressure
Lipids

Cite this

Bohula, E. A., Wiviott, S. D., McGuire, D. K., Inzucchi, S. E., Kuder, J., Im, K. A., ... Scirica, B. M. (2018). Cardiovascular safety of lorcaserin in overweight or obese patients. New England Journal of Medicine, 379(12), 1107-1117. https://doi.org/10.1056/NEJMoa1808721

Cardiovascular safety of lorcaserin in overweight or obese patients. / Bohula, E. A.; Wiviott, S. D.; McGuire, D. K.; Inzucchi, S. E.; Kuder, J.; Im, K. A.; Fanola, Christina; Qamar, A.; Brown, C.; Budaj, A.; Garcia-Castillo, A.; Gupta, M.; Leiter, L. A.; Weissman, N. J.; White, H. D.; Patel, T.; Francis, B.; Miao, W.; Perdomo, C.; Dhadda, S.; Bonaca, M. P.; Ruff, C. T.; Keech, A. C.; Smith, S. R.; Sabatine, M. S.; Scirica, B. M.

In: New England Journal of Medicine, Vol. 379, No. 12, 20.09.2018, p. 1107-1117.

Research output: Contribution to journalArticle

Bohula, EA, Wiviott, SD, McGuire, DK, Inzucchi, SE, Kuder, J, Im, KA, Fanola, C, Qamar, A, Brown, C, Budaj, A, Garcia-Castillo, A, Gupta, M, Leiter, LA, Weissman, NJ, White, HD, Patel, T, Francis, B, Miao, W, Perdomo, C, Dhadda, S, Bonaca, MP, Ruff, CT, Keech, AC, Smith, SR, Sabatine, MS & Scirica, BM 2018, 'Cardiovascular safety of lorcaserin in overweight or obese patients', New England Journal of Medicine, vol. 379, no. 12, pp. 1107-1117. https://doi.org/10.1056/NEJMoa1808721
Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im KA et al. Cardiovascular safety of lorcaserin in overweight or obese patients. New England Journal of Medicine. 2018 Sep 20;379(12):1107-1117. https://doi.org/10.1056/NEJMoa1808721
Bohula, E. A. ; Wiviott, S. D. ; McGuire, D. K. ; Inzucchi, S. E. ; Kuder, J. ; Im, K. A. ; Fanola, Christina ; Qamar, A. ; Brown, C. ; Budaj, A. ; Garcia-Castillo, A. ; Gupta, M. ; Leiter, L. A. ; Weissman, N. J. ; White, H. D. ; Patel, T. ; Francis, B. ; Miao, W. ; Perdomo, C. ; Dhadda, S. ; Bonaca, M. P. ; Ruff, C. T. ; Keech, A. C. ; Smith, S. R. ; Sabatine, M. S. ; Scirica, B. M. / Cardiovascular safety of lorcaserin in overweight or obese patients. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 12. pp. 1107-1117.
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abstract = "BACKGROUND Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS At 1 year, weight loss of at least 5{\%} had occurred in 1986 of 5135 patients (38.7{\%}) in the lorcaserin group and in 883 of 5083 (17.4{\%}) in the placebo group (odds ratio, 3.01; 95{\%} confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0{\%} per year in the lorcaserin group and 2.1{\%} per year in the placebo group (hazard ratio, 0.99; 95{\%} CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1{\%} per year and 4.2{\%} per year, respectively (hazard ratio, 0.97; 95{\%} CI, 0.87 to 1.07; P = 0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P = 0.04). CONCLUSIONS In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo.",
author = "Bohula, {E. A.} and Wiviott, {S. D.} and McGuire, {D. K.} and Inzucchi, {S. E.} and J. Kuder and Im, {K. A.} and Christina Fanola and A. Qamar and C. Brown and A. Budaj and A. Garcia-Castillo and M. Gupta and Leiter, {L. A.} and Weissman, {N. J.} and White, {H. D.} and T. Patel and B. Francis and W. Miao and C. Perdomo and S. Dhadda and Bonaca, {M. P.} and Ruff, {C. T.} and Keech, {A. C.} and Smith, {S. R.} and Sabatine, {M. S.} and Scirica, {B. M.}",
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TY - JOUR

T1 - Cardiovascular safety of lorcaserin in overweight or obese patients

AU - Bohula, E. A.

AU - Wiviott, S. D.

AU - McGuire, D. K.

AU - Inzucchi, S. E.

AU - Kuder, J.

AU - Im, K. A.

AU - Fanola, Christina

AU - Qamar, A.

AU - Brown, C.

AU - Budaj, A.

AU - Garcia-Castillo, A.

AU - Gupta, M.

AU - Leiter, L. A.

AU - Weissman, N. J.

AU - White, H. D.

AU - Patel, T.

AU - Francis, B.

AU - Miao, W.

AU - Perdomo, C.

AU - Dhadda, S.

AU - Bonaca, M. P.

AU - Ruff, C. T.

AU - Keech, A. C.

AU - Smith, S. R.

AU - Sabatine, M. S.

AU - Scirica, B. M.

PY - 2018/9/20

Y1 - 2018/9/20

N2 - BACKGROUND Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P = 0.04). CONCLUSIONS In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo.

AB - BACKGROUND Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined. METHODS We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial. RESULTS At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P = 0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P = 0.04). CONCLUSIONS In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo.

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