Collaborative Atorvastatin Diabetes Study (CARDS)

1
Collaborative Atorvastatin Diabetes Study (CARDS)
Atorvastatin 10 mg (n1428)
Patient Population

• Type 2 diabetes mellitus
• Men and women 4075 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

2838 patients
4-year follow-up
Double-blind placebo (n1410)

• Primary endpoint time to first major CV event
  (CHD death, nonfatal MI, unstable angina,
  resuscitated cardiac arrest, coronary
  revascularization, stroke
• Secondary endpoints total mortality, any CV
  endpoint, lipids, and lipoproteins

Colhoun HM et al. Lancet 2004364685-696.
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CARDS Patient Baseline Characteristics
Placebo(n 1410) Atorvastatin(n 1428)
Age
Mean (SD) years 61.8 (8.0) 61.5 (8.3)
lt60 529 (38) 558 (39)
6070 708 (50) 703 (49)
gt70 173 (12) 167 (12)
Women 453 (32) 456 (32)
White ethnicity 1326 (94) 1350 (95)
BMI
Mean (SD), kg/m2 28.8 (3.5) 28.7 (3.6)
Obese (BMI gt30 kg/m2) 538 (38) 515 (36)
Colhoun HM et al. Lancet 2004364685-696.
Reprinted with permission from Elsevier.
3
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 (104212)1.67 (1.172.40) 150 (106212)1.70 (1.202.40)
Median (interquartile range)
Colhoun HM et al. Lancet 2004364685-696.
Reprinted with permission from Elsevier.
4
CARDS Lipid Levels by Treatment
Total Cholesterol (mg/dL)Average difference
26,54 mg/dL Plt0.0001
LDL Cholesterol (mg/dL)Average difference
40,46 mg/dL Plt0.0001
Placebo
Placebo
Median LDL-C (mg/dL)
Atorvastatin
Median TC (mg/dL)
Atorvastatin
Years of Study
Years of Study
Colhoun HM et al. Lancet 2004364685-696.
Reprinted with permission from Elsevier.
5
CARDS Effect of Atorvastatin on the Primary
Endpoint Major CV Events Including Stroke
Relative Risk Reduction 37 (95 CI, 1752)P
0.001
Placebo127 events
Cumulative Hazard, ()
Atorvastatin83 events
0
1
2
3
4
4.75
Years
14101428
13511392
PlaceboAtorvastatin
13061361
10221074
651694
305328
Colhoun HM et al. Lancet 2004364685-696.
Reprinted with permission from Elsevier.
6
CARDS Adverse and Serious Adverse Events
Type of Event Patients () with Event Patients () with Event
Type of Event Placebo(n 1410) Atorvastatin 10 mg(n 1428)
Serious adverse eventpossibly associated with study drug 20 (1.1) 19 (1.1)
Discontinued for AE 145 (10) 122 (9)
Rhabdomyolysis 0 0
Myopathy AE report 1 (0.1) 1 (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 2004364685-696.
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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 2,838 Atorvastatin 10 37 (p.001)
AFCAPS 155 6,605 Lovastatin 2040 44 (NS)
HPS 2,912 7,150 Simvastatin 40 33 (p.0003)
ASCOT 2,532 10,305 Atorvastatin 10 16 (NS)
PROSPER 623 5,804 Pravastatin 40 27 (NS)
HHS 135 4,081 Gemfibrozil 1200 68 (NS)
By history Prospective trial in diabetic
subjects others are subgroup analyses Mean 30
mg/d Type 1 or 2 diabetes
Bays H et al. Future Cardiology 2005139-59.
Colhoun HM et al. Lancet 2004364685-696.
Downs JR et al. JAMA 19982791615-1622. HPS
Collaborative Group. Lancet 20033612005-2016.
Sever PS et al. Lancet 20033611149-1158.
Shepherd J et al. Lancet 20023601623-1630.
Koskinen P et al. Diabetes Care 199215820-825.
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Secondary 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,
4S Reanalysis 202483 4,444 Simvastatin 2040 55 (p.002)42 (p.001)
CARE 586 4,159 Pravastatin 40 25 (p.05)
LIPID 1,077 9,014 Pravastatin 40 19 (NS)
LIPS 202 1,677 Fluvastatin 80 47 (p.04)
HPS 3,051 13,386 Simvastatin 40 18 (p.002)
4D 1,255 1,255 Atorvastatin 20 8 (NS)
VA-HIT 769 2,351 Gemfibrozil 1,200 32 (p.004)
DAIS 418 418 Fenofibrate 200 23 (NS)
Type 1 or 2 diabetes Prospective trial in
diabetic subjects others are subgroup
analyses Angiographic study
Includes stroke in 4D and VA-HIT By history By
history or glucose ?126 mg/dL
Bays H et al. Future Cardiology 2005139-59.
Pyörälä K et al. Diabetes Care 199720614-620.
Haffner SM et al. Arch Intern Med
19991592661-2667. Goldberg RB et al.
Circulation 1998982513-2519. Keech A et al.
Diabetes Care 2003262713-2721. Serruys PWJC
et al. JAMA 20022873215-3222. HPS
Collaborative Group. Lancet 20033612005-2016.
Wanner C. Presented at ASN annual meeting, 2004.
Rubins HB et al. Arch Intern Med
20021622597-2604. DAIS Investigators. Lancet
2001357905-910.