Cardiovascular responses to weight management and sibutramine in high-risk subjects: an analysis from the SCOUT trial.

AIMS The Sibutramine Cardiovascular OUTcomes (SCOUT) trial is a randomized, double-blind comparison of sibutramine vs. placebo, in addition to standard care for weight management, in overweight/obese subjects with an increased risk of cardiovascular disease. The study had an initial single-blind, 6-week lead-in period with sibutramine plus weight management. We report the cardiovascular responses and weight loss during this period. METHODS AND RESULTS A total of 10,742 subjects received treatment in the lead-in period; 97% had cardiovascular disease, 88% hypertension and 84% type 2 diabetes. Body weight decreased (median 2.2 kg [5th, 95th percentile changes -6.2, 0.5]); waist circumference was reduced by 2.0 cm (men: -8.5, 2.9; women: -9.0, 3.0), systolic blood pressure fell by 3.0 mmHg (-23.5, 12.5) and diastolic by 1.0 mmHg (-13.5, 10.0). Pulse rate increased by 1.5 b.p.m. (-11.0, 13.5). All changes were statistically significant (P < 0.001). Two consecutive increases in blood pressure or pulse rate of >10 mmHg/b.p.m. were observed in 4.7 and 3.5% of subjects, respectively. Fifteen subjects (0.1%) died; 10 deaths were attributed to a cardiovascular cause, equivalent to 1.2 and 0.8 deaths per 100 years of exposure, respectively. CONCLUSION Six-week treatment with sibutramine appears to be efficacious, tolerable and safe in this high-risk population for whom sibutramine is usually contraindicated.

[1]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[2]  K. Dickstein,et al.  Weight-change as a prognostic marker in 12 550 patients following acute myocardial infarction or with stable coronary artery disease. , 2006, European heart journal.

[3]  A. Diedrich,et al.  Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects , 2006, Clinical pharmacology and therapeutics.

[4]  T. Wadden,et al.  Randomized trial of lifestyle modification and pharmacotherapy for obesity. , 2005, The New England journal of medicine.

[5]  Arya M. Sharma.  Does pharmacologically induced weight loss improve cardiovascular outcome? Sibutramine pharmacology and the cardiovascular system , 2005 .

[6]  W. James.  The SCOUT study: risk-benefit profile of sibutramine in overweight high-risk cardiovascular patients , 2005 .

[7]  N. Poulter,et al.  Different time course for prevention of coronary and stroke events by atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA). , 2005, The American journal of cardiology.

[8]  Arya M. Sharma,et al.  Paradoxical Effect of Sibutramine on Autonomic Cardiovascular Regulation , 2002, Clinical autonomic research : official journal of the Clinical Autonomic Research Society.

[9]  T. Pischon,et al.  Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients , 2005, Clinical Autonomic Research.

[10]  C. Erem,et al.  Effect of low-dose metoprolol in combination with sibutramine therapy in normotensive obese patients: a randomized controlled study , 2004, International Journal of Obesity.

[11]  G. Mancia,et al.  European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force Of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). , 2004, Archives des maladies du coeur et des vaisseaux.

[12]  S. Priori,et al.  2003 European Society of Hypertension-European Society of Cardiology Guidelines for the Management of Arterial Hypertension , 2004, Heart Drug.

[13]  T. Wadden,et al.  Behavioral treatment of obesity. , 2003, Endocrinology and metabolism clinics of North America.

[14]  Arya M. Sharma,et al.  Selective Impairment in Sympathetic Vasomotor Control With Norepinephrine Transporter Inhibition , 2003, Circulation.

[15]  Abdissa Negassa,et al.  Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study , 2003, The Lancet.

[16]  K. Flegal,et al.  Prevalence and trends in obesity among US adults, 1999-2000. , 2002, JAMA.

[17]  J. Scholze.  [Sibutramine in clinical practice - a PMS-study with positive effects on blood pressure and metabolic parameters]. , 2002, Deutsche medizinische Wochenschrift.

[18]  A. Keech,et al.  Relationship Between Lipid Levels and Clinical Outcomes in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Trial: To What Extent Is the Reduction in Coronary Events With Pravastatin Explained by On-Study Lipid Levels? , 2002, Circulation.

[19]  N. Cutler,et al.  Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial , 2002, Journal of Human Hypertension.

[20]  A. Tremblay,et al.  Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet–exercise intervention , 2001, International Journal of Obesity.

[21]  S. Toubro,et al.  The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction , 1999, International Journal of Obesity.

[22]  Treatment of Obesity in Adults.  Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health. , 1998, Obesity research.

[23]  Janzen,et al.  The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators. , 1996, The Canadian journal of cardiology.