Relationship of Glycemia to Cardiovascular Disease ... - Lipids Online

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Non-UKPDS Trials: Metformin vs. Conventional Treatment When one looks at metformin data in studies outside of the United Kingdom Prospective Diabetes Study, however, there apparently is no evidence of cardiovascular benefit, as in this meta-analysis conducted by Saenz et al. (2005). Furthermore, these other studies tend to have small numbers of patients. Reference: Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(3):CD002966. Nissen and Wolski Meta-analysis: analysis: Rates of Myocardial Infarction and Death from Cardiovascular Causes UKPDS Rosiglitazone Control Odds Ratio (95% CI) p value Myocardial Infarction Small trials 44/10,285 (0.43%) 22/6105 (0.36%) 1.45 (0.88–2.39) 0.15 DREAM 15/2,635 (0.57%) 9/2634 (0.34%) 1.65 (0.74–3.68) 0.22 ADOPT 27/1,456 (1.85%) 41/2895 (1.44%) 1.33 (0.80–2.21) 0.27 Total 86/14371 (0.60%) 72/11634 (0.62%) 1.43 (1.03–1.98) 0.03 Death from Cardiovascular Causes Small trials 25/6,845 (0.36%) 7/3,980 (0.18%) 2.40 (1.17–4.91) 0.02 DREAM 12/2,635 (0.46%) 10/2,634 (0.38%) 1.20 (0.52–2.78) 0.67 ADOPT 2/1,456 (0.14%) 5/2,895 (0.17%) 0.80 (0.17–3.86) 0.78 Total 39/10648 (0.37%) 22/9188 (0.24%) 1.64 (0.98–2.74) 0.06 CI = confidence interval; UKPDS = United Kingdom Prospective Diabetes Study Nissen SE, Wolski K. N Engl J Med. 2007; 356. 2457–2471. Copyright © 2007 Massachusetts Medical Society. All rights reserved. Slide Source Lipids Online Slide Library www.lipidsonline.org Nissen and Wolski Meta-analysis: Rates of Myocardial Infarction and Death from Cardiovascular Causes Based on their meta-analysis of the cardiovascular safety of rosiglitazone, Nissen and Wolski (2007) raised the question of whether there is a risk for myocardial infarction among diabetic patients treated with rosiglitazone versus other treatments. In the studies they evaluated, cardiovascular endpoints were neither adjudicated nor were they primary endpoints; the mean follow-up period for most of the evaluated studies was only 6 months. These observations raised concern about whether the preclinical studies of rosiglitazone, which had shown the drug to have antiatherosclerotic affects, were relevant to patients with type 2 diabetes. Since then, there have been numerous studies whose findings conflict with those of this meta-analysis. Reference: Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457-2471. Source: Lipids Online Slide Library (www.lipidsonline.org) Page 14 of 36 © 2009 Baylor College of Medicine, Houston, Texas
Balance of Evidence: Is Rosiglitazone Associated With Cardiovascular Risk? MI = myocardial infarction MET = metformin SU = sulfonylurea PIO = pioglitazone FDA Analysis MI signal with insulin and nitrates GSK ICT analysis MI signal Nissen et al. MI signal ACCORD Mortality not linked to to any specific diabetes drug ADOPT No significant risk Comparable to to MET, SU Lago et et al. Lancet. No significant risk Comparable to to PIO RECORD No significant risk Comparable to to MET, SU McAfee et et al. No significant risk Comparable to to MET/SU Rosen et al. No significant risk Comparable to to PIO “…[W]e believe that only prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone will resolve the controversy about its safety.” — Diamond et al., 2007 Diamond GA, et al. Ann Intern Med. 2007;147:578–581 | Home PD. N Engl J Med. 2007;357:28–38 | Krall RL. Lancet. 2007;369:1995–1996. | Lago RM, et al. Lancet. 2007;370:1129–1136 | McAfee AT, et al. Pharmacoepidemiol Drug Saf. 2007; 16:711–725 | Nissen SE, et al. N Engl J Med. 2007;356:2457–2471 | Rosen CJ. N Engl J Med. 2007;357:844–846. Slide Source Lipids Online Slide Library www.lipidsonline.org Balance of Evidence: Is Rosiglitazone Associated With Cardiovascular Risk? Recently published data from the ACCORD and ADVANCE studies — both of which evaluated whether lowering the hemoglobin A 1c concentration (below its current recommended target of 7%) is associated with cardiovascular benefit — did not show any link between rosiglitazone and an excess risk for myocardial infarction. Furthermore, a meta-analysis conducted by Lago et al. (2007) did not show any significant risk for cardiovascular death when they compared rosiglitazone to other treatments, particularly pioglitazone. The interim analysis of the RECORD trial also showed that rosiglitazone carries a risk for cardiovascular disease that is comparable to metformin and sulfonylureas. ACCORD = Action to Control Cardiovascular Risk in Diabetes ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation RECORD = Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes References: Diamond GA, Bax L, Kaul S. Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death. Ann Intern Med. 2007;147:578-581. Home PD, Pocock SJ, Beck-Nielsen H, et al, for the RECORD Study Group. Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med. 2007;357:28-38. Krall RL. Cardiovascular safety of rosiglitazone. Lancet. 2007;369:1995-1996. Source: Lipids Online Slide Library (www.lipidsonline.org) Page 15 of 36 © 2009 Baylor College of Medicine, Houston, Texas
Page 1 and 2: Relationship of Glycemia to Cardiov
Page 3 and 4: TNT Study: Impact of Glucometabolic
Page 5 and 6: The Proinflammatory Milieu in Ather
Page 7 and 8: STOP-NIDDM Trial: Acarbose Prevents
Page 9 and 10: Controlling Postprandial Hyperglyce
Page 11 and 12: DCCT-EDIC: Long-term Risk of Macrov
Page 13: Non-UKPDS Trials: Metformin vs. Oth
Page 17 and 18: PROactive: Difference in Number of
Page 19 and 20: Factors Possibly Contributing to th
Page 21 and 22: Annual Incidence of Congestive Hear
Page 23 and 24: ORIGIN = Outcome Reduction with Ini
Page 25 and 26: PERISCOPE: Study Design IVUS at Scr
Page 27 and 28: PERISCOPE: Intravascular Ultrasound
Page 29 and 30: APPROACH: Using Intravascular Ultra
Page 31 and 32: STENO-2: Reduction in Cardiovascula
Page 33 and 34: STENO-2: Risk-Factor Targets Attain
Page 35 and 36: SANDS Randomized Trial: Effects of

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