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Collaborative Atorvastatin Diabetes Collaborative Atorvastatin Diabetes Study (CARDS)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;364:685-696.

Patient Patient PopulationPopulation

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 2838 patientspatients

4-year follow-up4-year follow-up

Atorvastatin 10 mg Atorvastatin 10 mg

(n=1428)(n=1428)

Double-blind placebo Double-blind placebo (n=1410)(n=1410)


CARDS: Patient Baseline CharacteristicsCARDS: Patient Baseline Characteristics

Placebo(n = 1410)

Atorvastatin(n = 1428)

Age

Mean (SD) years 61.8 (8.0) 61.5 (8.3)

<60 529 (38%) 558 (39%)

60–70 708 (50%) 703 (49%)

>70 173 (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 >30 kg/m2) 538 (38%) 515 (36%)

Colhoun HM et al. Lancet 2004;364:685-696. Reprinted with permission from Elsevier.


CARDS: Patient Baseline LipidsCARDS: 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)Median (interquartile range)Colhoun HM et al. Lancet 2004;364:685-696. Reprinted with permission from Elsevier.


0

80

160

240

CARDS: Lipid Levels by TreatmentCARDS: Lipid Levels by Treatment

Total Cholesterol (mg/dL)Total Cholesterol (mg/dL)

Average difference Average difference 26%,26%,

5454 mg/dL; P<0.0001 mg/dL; P<0.0001

Med

ian

TC

(m

g/d

L)*

Years of Study

0 1 2 3 4 4.50

40

80

120

160

Med

ian

LD

L-C

(m

g/d

L)*

Years of Study

0 1 2 3 4 4.5

LDL Cholesterol (mg/dL)LDL Cholesterol (mg/dL)

Average difference Average difference 40%,40%,

4646 mg/dL; P<0.0001 mg/dL; P<0.0001

Atorvastatin

Atorvastatin

PlaceboPlacebo



0

5

10

15

CARDS: Effect of Atorvastatin on the Primary CARDS: Effect of Atorvastatin on the Primary Endpoint: Major CV Events Including StrokeEndpoint: Major CV Events Including Stroke

Cum

ula

tive H

aza

rd, (%

)

Years0 1 2 3 4

Relative Risk Reduction 37% (95% CI, 17–52)Relative Risk Reduction 37% (95% CI, 17–52)P = 0.001P = 0.001

14101428

13511392

PlaceboAtorvastatin

4.75

13061361

10221074

651694

305328

Placebo127 events

Atorvastatin83 events



CARDS: Adverse and Serious Adverse CARDS: Adverse and Serious Adverse EventsEvents

Type of Event

Patients (%) with 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 2004;364:685-696.


Primary Prevention Trials of Lipid-Altering Primary Prevention Trials of Lipid-Altering Therapy Including Patients with DiabetesTherapy Including Patients with Diabetes

Trial Diabetic,*

n

Total N in

StudyLipid-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 20–40 ‡ –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)

Bays H et al. Bays H et al. Future CardiologyFuture Cardiology 2005;1:39-59. | 2005;1:39-59. | Colhoun HM et al. Colhoun HM et al. LancetLancet 2004;364:685-696. | 2004;364:685-696. | Downs Downs JR et al. JR et al. JAMAJAMA 1998;279:1615-1622. | HPS Collaborative Group. 1998;279:1615-1622. | HPS Collaborative Group. LancetLancet 2003;361:2005- 2003;361:2005-2016. | Sever PS et al. 2016. | Sever PS et al. LancetLancet 2003;361:1149-1158. | Shepherd J et al. 2003;361:1149-1158. | Shepherd J et al. LancetLancet 2002;360:1623- 2002;360:1623-1630. | Koskinen P et al. 1630. | Koskinen P et al. Diabetes CareDiabetes Care 1992;15:820-825. 1992;15:820-825.

* By history* By history† † Prospective trial in diabetic subjects; others are subgroup analysesProspective trial in diabetic subjects; others are subgroup analyses‡ ‡ Mean 30 mg/dMean 30 mg/d§ Type 1 or 2 diabetes§ Type 1 or 2 diabetes


Secondary Prevention Trials of Lipid-Altering Secondary Prevention Trials of Lipid-Altering Therapy Including Patients with DiabetesTherapy Including Patients with Diabetes

Bays H et al. Bays H et al. Future Cardiology Future Cardiology 2005;1:39-59. | Pyörälä K et al. 2005;1:39-59. | Pyörälä K et al. Diabetes CareDiabetes Care 1997;20:614-620. | Haffner SM et 1997;20:614-620. | Haffner SM et al. al. Arch Intern MedArch Intern Med 1999;159:2661-2667. | Goldberg RB et al. 1999;159:2661-2667. | Goldberg RB et al. CirculationCirculation 1998;98:2513-2519. | Keech A et al. 1998;98:2513-2519. | Keech A et al. Diabetes Diabetes Care 2003;26:2713-2721. | Serruys PWJC et al. Care 2003;26:2713-2721. | Serruys PWJC et al. JAMAJAMA 2002;287:3215-3222. | HPS Collaborative Group. 2002;287:3215-3222. | HPS Collaborative Group. LancetLancet 2003;361:2005-2016. | Wanner C. Presented at ASN annual meeting, 2004. | Rubins HB et al. 2003;361:2005-2016. | Wanner C. Presented at ASN annual meeting, 2004. | Rubins HB et al. Arch Intern Arch Intern MedMed 2002;162:2597-2604. | DAIS Investigators. 2002;162:2597-2604. | DAIS Investigators. LancetLancet 2001;357:905-910. 2001;357:905-910.

Trial

Diabetic,

n

Total N in

StudyLipid-Altering

Drug, mg/d

CHD* Risk vs Placebo in Diabetic

Patients, %

4S Reanalysis

202†483‡

4,444 Simvastatin 20–40 –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)

*Includes stroke in 4D and VA-HIT*Includes stroke in 4D and VA-HIT††By historyBy history‡‡By history or glucose By history or glucose 126 mg/dL126 mg/dL

§ Type 1 or 2 diabetes§ Type 1 or 2 diabetes¶¶ Prospective trial in diabetic subjects; others Prospective trial in diabetic subjects; others

are subgroup analysesare subgroup analyses|||| Angiographic study Angiographic study

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