CARE: Cholesterol and Recurrent Events Trial

1
CARE Cholesterol and Recurrent Events Trial

• Purpose
• To determine whether pravastatin reduces risk of
  coronary events in patients with average
  cholesterol and previous MI
• Reference
• Sacks FM, Pfeffer MA, Moye LA et al. for the
  Cholesterol and Recurrent Events Trial
  Investigators. The effect of pravastatin on
  coronary events after myocardial infarction in
  patients with average cholesterol levels. New
  Engl J Med 199633510019.

2
CARE Cholesterol and Recurrent Events Trial-
TRIAL DESIGN -

• Design
• Multicenter, multinational, randomized,
  double-blind, placebo-controlled
• Patients
• 4159 patients (3583 men, 576 women), aged 2175
  years, with previous MI, and average levels of
  total cholesterol (lt240 mg/dL, lt6.2 mol/L) and
  LDL cholesterol (115174 mg/dL, 3.04.5 mmol/L)
• Follow up and primary endpoint
• Primary combined endpoint fatal coronary event
  or nonfatal MI. Median 5 years follow up
• Treatment
• Placebo or pravastatin 40 mg each evening

3
CARE Cholesterol and Recurrent Events Trial-
RESULTS -

• In pravastatin group, compared with placebo,
  significant reduction in
• Combined endpoint of nonfatal MI or fatal
  coronary event
• Myocardial revascularization procedures
• Stroke
• Major coronary events, in both over- and
  under-60s, with greater reduction in women than
  men
• Reduction in major coronary events dependent on
  baseline LDL cholesterol, with no reduction if
  lt125 mg/dL (lt3.2 mmol/L)
• No difference in overall mortality or in
  noncardiovascular death, including death from
  cancer or violence
• With pravastatin, total and LDL cholesterol and
  triglycerides reduced during follow up by 20,
  28 and 14, respectively HDL cholesterol
  increased by 5
• Drug well tolerated similar withdrawal rate in
  both groups

4
CARE Cholesterol and Recurrent Events Trial-
RESULTS continued -

Nonfatal MI or death from coronary heart disease
(CHD)
Incidence
15
()
10
5
Relative risk reduction 24
Placebo
P0.003
Pravastatin
0
0
1
2
3
4
5
Years after randomization
Sacks et al. N Engl J Med 199633510019.

5
CARE Cholesterol and Recurrent Events Trial-
RESULTS continued -

Major cardiovascular outcomes
Placebo
Pravastatin
Risk reduction,
P
n2078
n2081
(95 CI)
()
()



Nonfatal MI or death from CHD
13.2
10.2
24 (936)
0.003



CABG or PTCA
18.8
14.1
27 (1537)
lt0.001



Stroke
3.8
2.6
31 (352)
0.03




CAGB, coronary artery bypass grafting
PTCA, percutaneous transluminal coronary
angioplasty
Sacks et al. N Engl J Med 199633510019.
6
CARE Cholesterol and Recurrent Events Trial-
RESULTS continued -

Major coronary events in subgroups
Placebo,
Pravastatin,
Risk reduction,
P
(events/n)
(events/n)
(95 CI)
Sex
Female
28 (80/290)
16 (46/286)
46 (2262)
0.001



Male
26 (469/1788)
21 (384/1795)
20 (830)
0.001



Age
lt60 years
26 (258/1003)
21 (217/1027)
20 (433)
0.02
gt60 years
27 (291/1075)
70 (213/1054)
27 (1238)
lt0.001



LDL, mg/dL (mmol/L)




lt125 (lt3.2)
21 (93/441)
22 (89/410)
3 (38 to 23)
0.85
125150 (3.23.9)
27 (311/1172)
20 (239/1183)
26 (1338)
lt0.001
gt150175 (gt3.94.5)
31 (145/465)
21 (102/488)
35 (1750)
0.008
Sacks et al. N Engl J Med 199633510019.
LDL cholesterol at time of recruitment
7
CARE Cholesterol and Recurrent Events Trial-
SUMMARY -

• In patients with previous MI and average total
  and LDL cholesterol, pravastatin reduced
• Combined endpoint of fatal coronary event or
  nonfatal MI
• Need for myocardial revascularization procedures
• Major coronary events, in men and women and in
  over- and under-60s
• Stroke