The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels

Authors: Sacks F, Pfeffer M, Moye L, Rouleau J, Rutherford J, Cole T, Braunwald E, et al. for the CARE investigators.
Source: New England Journal of Medicine. 335:1001-9. October 3, 1996.
Institutions: Multi-institutional in the US and Canada.
Financial support: Bristol-Myers Squibb.



Lowering cholesterol in hypercholesterolemic patients with coronary artery disease has been shown to reduce recurrent events. The same has not been demonstrated clearly for patients with normal cholesterol levels. Since the majority of patients with coronary disease have cholesterol levels in the average range, this question is an important one. The Cholesterol and Recurrent Events Trial was designed to investigate this issue. Post-MI patients with average cholesterol levels were randomized to therapy with pravastatin or placebo and followed for an average of 5 years.



Authors' Discussion

The authors note that, in post-MI patients, reducing cholesterol levels from average values to around 100 mg/dl significantly reduced coronary events, although not overall mortality. This effect was seen in subgroups in which the benefit of lowering cholesterol was previously unclear (women, patients over 60). The relationship between baseline LDL and risk reduction is stressed -- the higher the baseline LDL level, the greater the risk reduction. Treating patients with baseline LDL's under 125 is probably not warranted.

The authors discuss the favorable effect of lipid-lowering therapy on the incidence of stroke. They argue against the importance of the increase in breast cancer, since the incidence in the placebo group was substantially lower than would have been expected, and other studies have failed to indicate a relation between breast cancer and statin therapy.

They calculate that, by treating 1000 patients for five years, 150 cardiovascular events could be prevented, and 51 patients could be prevented from having one or more events.


Once again (see "a note on combining endpoints" in the summary on digoxin in CHF), I don't think the combined endpoint "death from CHD or non-fatal MI" is particularly useful from a clinical standpoint, although it makes sense patho-physiologically. I believe the individual endpoints (MI, total mortality) are the most significant.

What are the main results of this study? In patients post-MI with average cholesterol levels, treatment for 5 years with a statin at a dose sufficient to lower LDL cholesterol from approximately 140 mg/dl to 100 mg/dl resulted in:

How do these results fit in with the two other big statin trials, the Scandinavian Simvastatin Survival Study (4S) (1) and the West of Scotland study (WOSCOP) (2, and reviewed here)?

Patients Secondary prevention.
Post-MI with high cholesterol.
Secondary prevention.
Post-MI with average cholesterol.
Primary prevention.
High risk patients with high cholesterol.
LDL cholesterol reduction From 188 to 122 From 139 to 98 From 192 to 142
Reduction in MI incidence 18.8% to 12.6%
Absolute reduction: 6.2%
11.1% to 8.7%
Absolute reduction: 2.4%
7.8% to 5.8%
Absolute reduction: 2.0%
Reduction in total mortality 12% to 8%
Absolute reduction: 4%
(9.4% to 8.7%)
4.1% to 3.2%
Absolute reduction: 0.9% (p=0.051)
Reduction in CABG or angioplasty 17.2% to 11.3%
Absolute reduction: 5.9%
18.8% to 14.1%
Absolute reduction: 4.7%
2.5% to 1.7%
Absolute reduction: 0.8%
Reduction in stroke rate 4.3% to 2.7% (includes TIA's)
Absolute reduction 1.6%
3.8% to 2.6%
Absolute reduction 1.2%
1.6% to 1.6%
No change

Overall, this table seems to show that the cardiovascular risk and treatment benefit are highest for secondary prevention with high cholesterol, intermediate for secondary prevention with average cholesterol and lowest for primary prevention. This is as we would expect. The lack of effect on overall mortality in CARE, contrasted with the marginal effect found in WOSCOP may be due to the larger sample size in WOSCOP. The higher intervention rate (CABG and PTCA) in CARE is probably due to the fact that this was a North American trial.

March 12, 1997

Reader comments

Date: Sun, 6 Apr 1997

Do you feel that this is a definitely a result of the lowering of LDL Cholesterol? Also, do you feel that this is a class effect? Would you be comfortable using any statin to reduce mortality regardless of available study or not?


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1. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-1389

2. Shepherd J, Cobbe S, Ford I, Isles C, Lorimer A, MacFarlane P, McKillop J, Packard C. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 1995;333:1301-1307

References related to this article from the NLM's PubMed database.

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