The Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholesterol Levels
Frank M. Sacks, M.D., Marc A. Pfeffer, M.D., Ph.D., Lemuel A. Moye, M.D., Ph.D., Jean L. Rouleau, M.D., J. Malcolm O. Arnold, M.D., Chuan-Chuan Wun, Ph.D., Barry Davis, M.D., Ph.D., Eugene Braunwald, M.D., for the Cholesterol and Recurrent Events Trial Investigators
N Engl J Med 1996; 335:1001-9
CARE - Study Design
Secondary prevention of CHD
80 centers in the US and Canada
4159 men and women aged 21 to 75 enrolled
3 to 20 months post-MI
Total-C < 240; LDL-C between 115 and 174; Triglycerides < 350 mg/dL
5 yr Treatment with Pravastatin 40 mg vs. placebo
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CARE - Study Endpoints
Primary:
CHD death or nonfatal MI
Secondary:
CHD death
Tertiary:
Total Mortality
Others:
Fatal MI, nonfatal MI, PTCA, CABG, Stroke
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CARE - Baseline Characteristics
86% male; 14% female
Mean age 59 ± 9 years
93% white
21% current smoker
42% hypertensive
14% diabetic
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CARE - Baseline Characteristics
Mean 10 ± 5 months post-MI
54% had prior PTCA / CABG
83% taking aspirin
41% taking b-blockers
40% taking calcium antagonists
15% taking ACEIs
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
Lipids at Baseline
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
Plasma Lipid Placebo Pravastatin
(n=2078) (n=2081)
Cholesterol (mg/dL)
Total 209 209
VLDL 27 27
LDL 139 139
HDL 39 39
Triglycerides (mg/dL) 155 156
Percent LDL Reduction on Treatment
P < 0.001 for all
comparisons
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
Fatal CHD or Nonfatal Myocardial Infarction (Primary Endpoint)
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
24% Risk Reduction
p = 0.003
Coronary Bypass Surgery or Angioplasty
27% Risk Reduction
p<0.001
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CARE - Achievement of Endpoints
Primary: CHD death or nonfatal MI
24% reduction p = 0.003
Secondary: CHD death
20% trend to reduction p = 0.10 (ns)
Tertiary: Total Mortality
9% trend to reduction p = 0.37 (ns)
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CARE - Achievement of Endpoints
Fatal MI
37% reduction (p=0.07)
Nonfatal MI
23% reduction (p=0.02)
Combined MI endpoints
25% reduction (p=0.002)
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CABG/PTCA/Combined
26% reduction (p=0.005)
PTCA
23% reduction (p=0.01)
Combined CABG/PTCA
27% risk reduction (p<0.001)
Other: Stroke
31% reduction (p=0.03)
CARE - Observations
Fatal CHD + nonfatal MI + CABG + PTCA
Women vs. Men: ? 46% vs. ? 20%
Current smokers vs. other: ? 33% vs. ? 22%
< 60 yr vs. > 60 yr: ? 20% vs. ? 27%
EF < 40% vs. > 40%: ? 28% vs. ? 23%
Hypertension, yes vs. no: ? 23% vs. ? 24%
Diabetes, yes vs. no: ? 25% vs. ? 23%
Prior PTCA/CABG, yes vs. no: ? 22% vs. ? 25%
p values for all subgroups were statistically significant
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
CARE - Observations
Baseline LDL influence on Events*
LDL 125-150 ??26% p < 0.001
LDL < 125 ??3% p = 0.85
LDL > 150-175 ?? ??? p = 0.008
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
*Events included; fatal CHD, nonfatal MI, CABG or Angioplasty
CARE - Safety
No difference in fatal and nonfatal primary cancers ... except
Breast Cancer:
Placebo (n=1)
Pravastatin (n=12), p=0.002*
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
Of the 12 breast cancer cases in the pravastatin group, all were nonfatal;
3 occurred in patients who had previously had breast cancer, 1 was ductal
carcinoma in situ, and 1 occurred in a patient who took pravastatin for
only six weeks.
Summary
Cholesterol lowering with pravastatin in patients with MI and TC < 240 mg/dL
Fatal CHD or nonfatal MI 24%
Fatal MI 37%
Nonfatal MI 23%
All MI, fatal or nonfatal 25%
Coronary artery bypass surgery 26%
Coronary angioplasty 23%
Stroke 31%
Reduced
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
Expected Number of Cardiovascular Events Preventable by Treating 1000 Patients with Pravastatin for Five Years
Number of Events
Events Total Group Age > 60 Women
Fatal CHD 11 27 10
Nonfatal Ml 26 46 83
CABG 25 32 34
PTCA 37 20 66
Strokes TIA 13 25 28
Other Cardiovascular 38 57 7
All Cardiovascular Events 150 207 228
Patients with ? 1 event pre- 51 71 97
vented
Sacks, F. et al, N Engl J Med 1996; 335:1001-9
Conclusion
These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels
Sacks, F. et al, N Engl J Med 1996; 335:1001-9