TY - JOUR
T1 - Lorcaserin and Renal Outcomes in Obese and Overweight Patients in the CAMELLIA-TIMI 61 Trial
AU - Scirica, Benjamin M.
AU - Bohula, Erin A.
AU - Dwyer, Jamie P.
AU - Qamar, Arman
AU - Inzucchi, Silvio E.
AU - McGuire, Darren K.
AU - Keech, Anthony C.
AU - Smith, Steven R.
AU - Murphy, Sabina A.
AU - Im, Kyungah
AU - Leiter, Lawrence A.
AU - Gupta, Milan
AU - Patel, Tushar
AU - Miao, Wenfeng
AU - Perdomo, Carlos
AU - Bonaca, Marc P.
AU - Ruff, Christian T.
AU - Sabatine, Marc S.
AU - Wiviott, Stephen D.
N1 - Funding Information:
This work was supported by Eisai Inc.
Funding Information:
Dr Scirica reports grants from Eisai during the conduct of the study; grants from AstraZenaca, Novartis, Merck, personal fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr Reddy’s Laboratory, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Merck, NovoNordisk, Sanofi, St. Jude’s Medical, other from Health [at] Scale outside the submitted work. Dr Bohula reports grants from Eisai during the conduct of the study; personal fees from Servier, Merck, NIH, Lexicon, Medscape, Academic CME, MD Conference Express, Paradigm, Novartis, grants from Amgen, Astra Zeneca, and Merck outside the submitted work. Dr Dwyer reports personal fees from Eisai, Inc. during the conduct of the study. Dr Inzucchi reports personal fees from Eisai during the conduct of the study; personal fees from Merck, Boehringer Ingelheim, Janssen, AstraZeneca, Novo Nordisk, Sanofi/Lexicon, Intarcia, Daiichi Sankyo, Alere, and VTV Therapeutics outside the submitted work. Dr McGuire reports personal fees from Eisai Inc during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Janssen Research and Development LLC, personal fees from Sanofi US, Merck Sharp and Dohme Corp, Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon, Esperion, Metavant, and Pfizer outside the submitted work. Dr Keech reports grants and personal fees from Abbott, personal fees from Amgen, Astra-Zeneca, grants and personal fees from Mylan, and personal fees from Pfizer outside the submitted work. Dr Leiter reports personal fees from Eisai Inc during the conduct of the study; grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and grants from GSK outside the submitted work. Drs Patel, Miao, and Perdomo report employment for Eisai. Dr Bonaca reports grants and personal fees from Amgen, AstraZeneca, Merck, personal fees from Aralez, Bayer, Janssen, Sanofi, and grants from MedImmune and Pfizer outside the submitted work. Dr Ruff reports grants and personal fees from Boehringer-Ingelheim, Daiichi Sankyo, personal fees from Bayer, Janssen, and Portola outside the submitted work. Dr Sabatine reports grants from Eisai during the conduct of the study; grants and personal fees from Amgen, Intarcia, AstraZeneca, Janssen Research and Development, Medicines Company, Medimmune, Merck, Novartis, BMS, CVS Caremark, Dyrnamix, Esperion, Alnylam, Ionis, and Myo-Kardia, and grants from Daiichi-Sankyo, Eisai, GlaxoSmithKline, Pfizer, Poxel, Takeda, Abbott Laboratories, Critical Diagnostics, Genzyme, Gilead, and Roche Diagnostics outside the submitted work. Dr Wiviott reports grants from AMGEN and Sonafi, grants and personal fees from Arena, Bristol Myers Squibb, Dai-ichi Sankyo, Eisai, Eli Lilly, Janssen, Merck, and AstraZeneca, personal fees from Aegerion, Allergan, Boehringer Ingelheim, Boston Clinical Research Institute, Icon Clinical, Lexicon, St Jude Medical, and Xoma outside the submitted work. Dr Smith reports personal fees from Eisai. Dr Im and Sabina A. Murphy report grants from Eisai. The remaining authors report no conflicts.
Publisher Copyright:
© 2018 American Heart Association, Inc.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - Background: Obesity is thought to increase renal hyperfiltration, thereby increasing albuminuria and the progression of renal disease. The effect of pharmacologically mediated weight loss on renal outcomes is not well-described. Lorcaserin, a selective serotonin 2C receptor agonist that promotes appetite suppression, led to sustained weight loss without any increased risk for major adverse cardiovascular (CV) events in the CAMELLIA-TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61). Methods: CAMELLIA-TIMI 61 randomly assigned 12 000 overweight or obese patients with or at high risk for atherosclerotic CV disease to lorcaserin or placebo on a background of lifestyle modification. The primary renal outcome was a composite of new or worsening persistent micro- or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death. Results: At baseline, 23.8% of patients had an estimated glomerular filtration rate (eGFR) <60 mL·min-1·1.73 m-2 and 19.0% had albuminuria (urinary albumin:creatinine ratio ≥30 mg/g). Lorcaserin reduced the risk of the primary renal composite outcome (4.2% per year versus 4.9% per year; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P=0.0064). The benefit was consistent across subpopulations at increased baseline CV and renal risk. Lorcaserin improved both eGFR and urinary albumin:creatinune ratio within the first year after randomization. The effect of lorcaserin on weight, hemoglobin A1c, and systolic blood pressure was consistent regardless of baseline renal function. Likewise, there was no excess in cardiovascular events in patients assigned to lorcaserin in comparison with placebo, regardless of renal function. After adjustment for baseline characteristics, those with evidence of kidney disease were at increased risk of major CV events. Compared with patients with an eGFR ≥90 mL·min-1·1.73 m-2, those with an eGFR 60-90 and those <60 mL·min-1·1.73 m-2 had HRs of 1.25 (95% CI, 1.01, 1.56) and 1.51 (95% CI, 1.17, 1.95), respectively (P for trend 0.0015). Likewise, compared with patients with no albuminuria (<30 mg/g), those microalbuminuria and those with macroalbuminuria had HRs of 1.46 (95% CI, 1.22, 1.74) and 2.10 (95% CI, 1.58, 2.80), respectively (P for trend <0.0001). Conclusions: Renal dysfunction was associated with increased CV risk in overweight and obese patients. When added to diet and lifestyle, lorcaserin reduced the rate of new-onset or progressive renal impairment in comparison with placebo.
AB - Background: Obesity is thought to increase renal hyperfiltration, thereby increasing albuminuria and the progression of renal disease. The effect of pharmacologically mediated weight loss on renal outcomes is not well-described. Lorcaserin, a selective serotonin 2C receptor agonist that promotes appetite suppression, led to sustained weight loss without any increased risk for major adverse cardiovascular (CV) events in the CAMELLIA-TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61). Methods: CAMELLIA-TIMI 61 randomly assigned 12 000 overweight or obese patients with or at high risk for atherosclerotic CV disease to lorcaserin or placebo on a background of lifestyle modification. The primary renal outcome was a composite of new or worsening persistent micro- or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death. Results: At baseline, 23.8% of patients had an estimated glomerular filtration rate (eGFR) <60 mL·min-1·1.73 m-2 and 19.0% had albuminuria (urinary albumin:creatinine ratio ≥30 mg/g). Lorcaserin reduced the risk of the primary renal composite outcome (4.2% per year versus 4.9% per year; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P=0.0064). The benefit was consistent across subpopulations at increased baseline CV and renal risk. Lorcaserin improved both eGFR and urinary albumin:creatinune ratio within the first year after randomization. The effect of lorcaserin on weight, hemoglobin A1c, and systolic blood pressure was consistent regardless of baseline renal function. Likewise, there was no excess in cardiovascular events in patients assigned to lorcaserin in comparison with placebo, regardless of renal function. After adjustment for baseline characteristics, those with evidence of kidney disease were at increased risk of major CV events. Compared with patients with an eGFR ≥90 mL·min-1·1.73 m-2, those with an eGFR 60-90 and those <60 mL·min-1·1.73 m-2 had HRs of 1.25 (95% CI, 1.01, 1.56) and 1.51 (95% CI, 1.17, 1.95), respectively (P for trend 0.0015). Likewise, compared with patients with no albuminuria (<30 mg/g), those microalbuminuria and those with macroalbuminuria had HRs of 1.46 (95% CI, 1.22, 1.74) and 2.10 (95% CI, 1.58, 2.80), respectively (P for trend <0.0001). Conclusions: Renal dysfunction was associated with increased CV risk in overweight and obese patients. When added to diet and lifestyle, lorcaserin reduced the rate of new-onset or progressive renal impairment in comparison with placebo.
KW - albuminuria
KW - kidney
KW - obesity
KW - serotonin receptor agonists
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U2 - 10.1161/CIRCULATIONAHA.118.038341
DO - 10.1161/CIRCULATIONAHA.118.038341
M3 - Article
C2 - 30586726
AN - SCOPUS:85060042495
SN - 0009-7322
VL - 139
SP - 366
EP - 375
JO - Circulation
JF - Circulation
IS - 3
ER -