Slide Source: Lipids Online Slide Library Collaborative Atorvastatin Diabetes Study (CARDS) Type 2 diabetes mellitus Men and women 40–75 years of age Primary CHD and stroke prevention LDL-C 160 mg/dL (4.14 mmol/L) TG 600 mg/dL (6.78 mmol/L) 1 additional RF – HTN (or on HTN treatment) – Retinopathy – Albuminuria – Current smoking Colhoun HM et al. Lancet 2004;364: Patient Population Primary endpoint: Primary endpoint: time to first major CV event (CHD death, nonfatal MI, unstable angina, resuscitated cardiac arrest, coronary revascularization, stroke Secondary endpoints: Secondary endpoints: total mortality, any CV endpoint, lipids, and lipoproteins 2838 patients 4-year follow-up Atorvastatin 10 mg (n=1428) Double-blind placebo (n=1410)

Slide Source: Lipids Online Slide Library CARDS: Patient Baseline Characteristics Placebo (n = 1410) Atorvastatin (n = 1428) Age Mean (SD) years61.8 (8.0)61.5 (8.3) <60529 (38%)558 (39%) 60–70708 (50%)703 (49%) >70173 (12%)167 (12%) Women453 (32%)456 (32%) White ethnicity1326 (94%)1350 (95%) BMI Mean (SD), kg/m (3.5)28.7 (3.6) Obese (BMI >30 kg/m 2 )538 (38%)515 (36%) Colhoun HM et al. Lancet 2004;364: Reprinted with permission from Elsevier.

Slide Source: Lipids Online Slide Library CARDS: Patient Baseline Lipids Placebo (n = 1410) Mean (SD) Atorvastatin (n = 1428) Mean (SD) Total cholesterol (mg/dL) (mmol/L) 207 (32) 5.35 (0.82) 207 (32) 5.36 (0.83) LDL cholesterol (mg/dL) (mmol/L) 117 (27) 3.02 (0.70) 118 (28) 3.04 (0.72) HDL cholesterol (mg/dL) (mmol/L) 55 (13) 1.42 (0.34) 54 (12) 1.39 (0.32) Triglycerides* (mg/dL) (mmol/L) 148 (104–212) 1.67 (1.17–2.40) 150 (106–212) 1.70 (1.20–2.40) *Median (interquartile range) Colhoun HM et al. Lancet 2004;364: Reprinted with permission from Elsevier.

Slide Source: Lipids Online Slide Library CARDS: Lipid Levels by Treatment Total Cholesterol (mg/dL) Average difference 26%, 54 mg/dL; P< Median TC (mg/dL)* Years of Study Median LDL-C (mg/dL)* Years of Study LDL Cholesterol (mg/dL) Average difference 40%, 46 mg/dL; P< Atorvastatin Placebo Colhoun HM et al. Lancet 2004;364: Reprinted with permission from Elsevier.

Slide Source: Lipids Online Slide Library CARDS: Effect of Atorvastatin on the Primary Endpoint: Major CV Events Including Stroke Cumulative Hazard, (%) Years Relative Risk Reduction 37% (95% CI, 17–52) P = Placebo Atorvastatin Placebo 127 events Atorvastatin 83 events Colhoun HM et al. Lancet 2004;364: Reprinted with permission from Elsevier.

Slide Source: Lipids Online Slide Library CARDS: Adverse and Serious Adverse Events Type of Event Patients (%) with Event Placebo (n = 1410) Atorvastatin 10 mg (n = 1428) Serious adverse event possibly associated with study drug 20 (1.1%)19 (1.1%) Discontinued for AE145 (10%)122 (9%) Rhabdomyolysis00 Myopathy AE report1 (0.1%) CPK 10  ULN 10 (0.7%)2 (0.1%) ALT 3  ULN 14 (1%)17 (1%) AST 3  ULN 4 (0.3%)6 (0.4%) Colhoun HM et al. Lancet 2004;364:

Slide Source: Lipids Online Slide Library Primary Prevention Trials of Lipid-Altering Therapy Including Patients with Diabetes Trial Diabetic,* n Total N in Study Lipid-Altering Drug, mg/d CHD* Risk vs Placebo in Diabetic Patients, % CARDS †2,838 Atorvastatin 10–37 (p=.001) AFCAPS1556,605Lovastatin 20–40 ‡–44 (NS) HPS §2,9127,150Simvastatin 40–33 (p=.0003) ASCOT2,53210,305Atorvastatin 10–16 (NS) PROSPER6235,804Pravastatin (NS) HHS1354,081Gemfibrozil 1200–68 (NS) Bays H et al. Future Cardiology 2005;1: | Colhoun HM et al. Lancet 2004;364: | Downs JR et al. JAMA 1998;279: | HPS Collaborative Group. Lancet 2003;361: | Sever PS et al. Lancet 2003;361: | Shepherd J et al. Lancet 2002;360: | Koskinen P et al. Diabetes Care 1992;15: * By history † Prospective trial in diabetic subjects; others are subgroup analyses ‡ Mean 30 mg/d § Type 1 or 2 diabetes

Slide Source: Lipids Online Slide Library Secondary Prevention Trials of Lipid-Altering Therapy Including Patients with Diabetes Bays H et al. Future Cardiology 2005;1: | Pyörälä K et al. Diabetes Care 1997;20: | Haffner SM et al. Arch Intern Med 1999;159: | Goldberg RB et al. Circulation 1998;98: | Keech A et al. Diabetes Care 2003;26: | Serruys PWJC et al. JAMA 2002;287: | HPS Collaborative Group. Lancet 2003;361: | Wanner C. Presented at ASN annual meeting, | Rubins HB et al. Arch Intern Med 2002;162: | DAIS Investigators. Lancet 2001;357: Trial Diabetic, n Total N in Study Lipid-Altering Drug, mg/d CHD* Risk vs Placebo in Diabetic Patients, % 4S Reanalysis 202† 483‡ 4,444Simvastatin 20–40–55 (p=.002) –42 (p=.001) CARE586†4,159Pravastatin 40–25 (p=.05) LIPID1,077‡9,014Pravastatin 40–19 (NS) LIPS §202†1,677Fluvastatin 80–47 (p=.04) HPS §3,051†13,386Simvastatin 40–18 (p=.002) 4D ¶1,255†1,255Atorvastatin 20 –8 (NS) VA-HIT769‡2,351Gemfibrozil 1,200–32 (p=.004) || DAIS ¶ || 418†418Fenofibrate 200–23 (NS) *Includes stroke in 4D and VA-HIT †By history ‡By history or glucose 126 mg/dL § Type 1 or 2 diabetes ¶Prospective trial in diabetic subjects; others are subgroup analyses || Angiographic study