Objective The aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces body weight and improves cardiometabolic risk factors in patients who are obese.
Design, setting, patients, interventions and results A prospective, double-blind, placebo-controlled trial (Atherosclerosis Underlying Development assessed by Intima–media Thickness in patients On Rimonabant (AUDITOR)) randomised 661 patients with abdominal obesity and metabolic syndrome to rimonabant or placebo for 30 months of treatment. The absolute change in the average value for six segments of far wall carotid intima–media thickness from baseline to month 30 was 0.010±0.095 mm in the rimonabant group and 0.012±0.091 mm in the placebo group (p=0.67). The annualised change was an increase of 0.005±0.042 mm for the rimonabant-treated group and 0.007±0.043 mm for the placebo-treated group (p=0.45).
Conclusions There was no difference in atherosclerosis progression between patients receiving rimonabant for 30 months and those receiving placebo for the primary efficacy measure (absolute change in carotid intima–media thickness). These findings are consistent with a similar study using coronary intravascular ultrasound and another study evaluating the occurrence of cardiovascular events. Our findings suggest that a 5% loss of body weight over a 30-month period with rimonabant is insufficient to modify atherosclerosis progression in the carotid artery in obese patients with metabolic syndrome.
Clinical trial registration information clinicaltrials.gov Identifier: NCT00228176.
- metabolic syndrome
- metabolic syndrome
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Role of sponsor: Sanofi-Aventis participated in discussions regarding study design and protocol development and provided logistical support during the trial. Monitoring of the study was performed by the sponsor, who also maintained the trial database. The CIMT end points were measured by the Imaging Core Laboratory (Imagepace, Cincinnati, Ohio, USA). The manuscript was prepared by the corresponding author and modified after consultation with the other authors. The sponsor was permitted to review the manuscript and suggest changes, but the final decision on content was exclusively retained by the academic authors.
Executive Committee of the AUDITOR Study: Daniel O'Leary, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA; Steven Nissen Cleveland Clinic, Cleveland, Ohio; Christopher Cannon, Brigham & Women's Hospital, Boston, Massachusetts; John Deanfield, University College, London, UK; Jean-Pierre Després, Québec Heart and Lung Institute, Quebec City, Quebec, Canada; Bernard Job (non-voting), Sanofi-Aventis, Paris, France; John Kastelein (Chair), Academic Medical Center, Amsterdam, The Netherlands.
Investigators: Canada: Ronald Akhras, Montréal, Canada; Victoria Bernstein, Vancouver, Canada; Laurie Breger, Pointe-Claire, Canada; Robert Dufour, Montréal, Canada; Jiri Frohlich, Vancouver, Canada; Dominique Garrel, Montréal, Canada; Rafik Habib, Laval, Canada; Lawrence Leiter, Toronto, Canada; Lew Pliamm, Toronto, Canada; Parmjit Sohal, Surrey, Canada; Paul Whitsitt, Oshawa, Canada. France: Yves Cottin, Dijon, France; Jacques Bonnet, Pessac, France; Michel Farnier, Dijon, France; Alain Simon, Paris, France. The Netherlands: Mieke Trip, Amsterdam, The Netherlands; Vicdan Kose, Breda, The Netherlands; Jeroen Tiebesl, Groningen, The Netherlands; Irma Agous, Leiden, The Netherlands; Antoaneta Wiersma-Maximova, Nijmegen, The Netherlands; Willem Wouter van Kempen, Rotterdam, The Netherlands; Lena de Schipper, Zoetermeer, The Netherlands; Rob Timmerman, Den Helder, The Netherlands; Frank Visseren, Utrecht, The Netherlands; Annette Bak, Utrecht, The Netherlands; Dick Basart, Hoorn, The Netherlands. Spain: Emili Ros, Barcelona, Spain; Jordi Salas, Reus, Spain; Fernando Civeira, Zaragoza, Spain; Xavier Formiguera, Badalona, Spain; Jordi Mesa, Barcelona, Spain; Xavier Pintó, Hospitalet del Llobregat, Spain. UK: Charles McCollum, Manchester, UK; Professor Paul Durrington, Manchester, UK; Professor John Betteridge, London, UK; Tahseen Chowdhury, London, UK; Peter Kopelman, London, UK; John Deanfield, London, UK. USA: Michael Davidson, Chicago, USA; Danny Sugimoto, Chicago, USA; Boris Kerzner, Baltimore, USA; James Mersey, Baltimore, USA; Alan Hirsch, Minneapolis, USA; Norman Lunde, Brooklyn Center, USA; James Zavoral, Edina, USA; Dean Kereiakes, Cincinnati, USA; Michael J Noss, Cincinnati, USA; Eli Roth, Cincinnati, USA; D.P. Suresh, Florence, USA; Christie Ballantyne, Houston, USA; Alan Garber, Houston, USA; James Pool, Houston, USA; Eliot Brinton, Salt Lake City, USA; Judith Kirstein, West Jordan, USA; Barry Lubin, Norfolk, USA; Lisa Harris, Virginia Beach, USA; John Hoekstra, Richmond, USA; Robert Call, Richmond, USA; Ronald Brazg, Renton, USA; Wayne Larson, Lakewood, USA; Kenneth Scherbarth, Tacoma USA; Larry Stonesifer, Federal Way, USA; James Stein, Madison, USA; Neville Bittar, Madison, USA.
Funding This study was funded by Sanofi-Aventis.
Competing interests DHO'L has consulted for the following pharmaceutical companies—Genzyme, Pfizer, AstraZeneca, Sanofi-Aventis, Schering, Imagepace, University of Washington—and he owns stock in Medpace, Inc. SNN has received research support through the Cleveland Clinic Center for Clinical Research (C5) within the last 5 years from AstraZeneca, Atherogenics, Eli Lilly, Novartis, Pfizer, Resverlogix, Takeda, Daiichi-Sankyo, and Sanofi-Aventis. He has consulted for a number of pharmaceutical companies without financial compensation. All honoraria, consulting fees or any other payments from any for-profit entity are paid directly to charity, so that he receives neither income nor a tax deduction. J-PD has received honoraria from the following pharmaceutical companies as a consultant or a lecturer: Abbott Laboratories, AstraZeneca, Eli Lilly Canada, Solvay Pharma, GlaxoSmithKline, Pfizer Canada Inc, Novartis. Furthermore, his laboratory has received research grants from some of the above companies and also from the Canadian Diabetes Association and the Canadian Institutes of Health Research. JED has received honoraria from the following pharmaceutical companies as a consultant or a lecturer: Novo Nordisk, Pfizer, Sanofi-Aventis, Novartis, Genzyme Roche. His laboratories received research grants from some of the above and from Colgate and Danone. He also receives grants from the British Heart Foundation, Medical Research Council, Diabetes UK and the Juvenile Diabetes Research Foundation (JDRF). BJ is the Clinical Study Director of AUDITOR and as such is representing the Sponsor Sanofi-Aventis within the Executive Committee as a non-voting member. JJPK has received consulting and lecture fees and research support from Pfizer, Roche, AstraZeneca, Merck, Novartis, Sanofi-Aventis, ISIS Pharmaceuticals, Eli Lilly, Genzyme and Schering-Plough. The department of FLJV received lecture or consulting fees from Merck, Genzyme, Eli Lilly and Pfizer.
Patient consent Obtained.
Ethics approval Approved by the institutional review boards of all participating centres.
Provenance and peer review Not commissioned; externally peer reviewed.
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