Cambridge Heart Antioxidant Study - CHAOS


Alpha-tocopherol for secondary prevention in ischemic heart disease.


A high dose of α-tocopherol would reduce subsequent risk of myocardial infarction (MI) and cardiovascular death in patients with established ischemic heart disease.

Study Design

Study Design:

Patients Enrolled: 2,002
Mean Follow Up: 510 days (median)
Mean Patient Age: 61.8

Patient Populations:

Angiographically proven coronary atherosclerosis


Prior use of vitamin supplements containing vitamin E

Primary Endpoints:

Nonfatal MI
Combination of nonfatal MI and cardiovascular death

Drug/Procedures Used:

α-tocopherol, 800 IU (first 546 patients) and 400 IU (remaining 421 patients on active medication); dose was reduced after early measurements indicated that lower amount would exceed physiological values.

Concomitant Medications:

Calcium antagonists (69.4% of a-tocopherol patients, 68.9% of placebo patients)
b-blocker (39.6% of a-tocopherol patients, 33.7% of placebo patients)
Nitrate (53,8% of a-tocopherol patients, 57.5% of placebo patients)
Aspirin, (mean of 82.9 mg/day for a-tocopherol patients, mean of 82.6 mg/day for placebo patients)

Principal Findings:

a-tocopherol treatment significantly reduced the risk of cardiovascular death and nonfatal MI (41 vs 64 events, relative risk 0.53 [95% CI 0.34-0.83]; p = 0.005).

a-tocopherol treatment significantly reduced the risk of nonfatal MI (14 vs. 41; 0.23 [0.11-0.47]; p= 0.0005).

There was a non-significant excess of cardiovascular deaths in the a-tocopherol group (27 vs. 23; 1.18 [0.62-2.27]; p = 0.61).

All-cause mortality was 36 of 1035 a-tocopherol-treated patients and 27 of 967 placebo patients.

Cost savings of $127 (A$181) and $578/patient randomized to vitamin E therapy compared with patients receiving placebo were found for Australian and US settings, respectively. Savings in the vitamin E group were due primarily to reduction in hospital admissions for AMI.


In patients with angiographically proven symptomatic coronary atherosclerosis, a-tocopherol treatment substantially reduces the rate of nonfatal MI, with beneficial effects apparent after 1 year of treatment. The Effect of A-Tocopherol on Cardiovascular Deaths requires further study.


1. Lancet 1996;347:781-6. Final results
2. American Journal of Cardiology 1998;82(4):414-7. Cost-effectiveness

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Risk, Coronary Artery Disease, Myocardial Infarction, Vitamin E, alpha-Tocopherol, Secondary Prevention, Coronary Angiography, Australia, Cost Savings

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