Myocardial infarction: beta-carotene increased mortality, and alpha-tocopherol had no clear benefit.

Clinical bottom line (level 1b)

  1. Men with a previous myocardial infarction who took beta-carotene were less likely to have another myocardial infarction (NNT = 24 at 6 years) , but were at increased risk of dying (NNH = 14 at 6 years) .
  2. Alpha-tocopherol had no clear effect on death from coronary heart disease or non-fatal myocardial infarction.
Rapola et al: Lancet 1997; 349: 1715-1720
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: community, Finland

1862 patients (aged mean 60, 100% male) with a previous myocardial infarction

Excluded if
  • use of vitamin E, vitamin A or beta-carotene supplements in doses that exceeded prespecified limits
  • chronic renal insufficiency
  • cirrhosis of the liver
  • alcoholism
  • other medical problems that might limit participation
  • anticoagulant therapy
  • proven malignant disease
  • angina (when walking on level ground)


    • Control Group: (n = 438, 438 analysed): placebo
    Experimental Group: (n = 466, 466 analysed): alpha-tocopherol ly
    Experimental Group: (n = 461, 461 analysed): beta-carotene 20 mg daily
    Experimental Group: (n = 497, 497 analysed): alpha-tocopherol 50 mg and beta-carotene 20 mg daily

    100% followed for 6 years
    Outcome notes:
    • non-fatal myocardial infarction : beta-carotene
    • death from coronary heart disease : beta-carotene
    • non-fatal myocardial infarction : alpha-tocopherol and beta-carotene
    • death from coronary heart disease : alpha-tocopherol and beta-carotene
    • non-fatal myocardial infarction : alpha-tocopherol

    The evidence

    beta-carotene v. placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    non-fatal myocardial infarction 6 years 55
    (12.6%)    		 39
    (8.46%)    		 33%
    (1% to 54%)    		 4.10%
    (0.0867% to 8.11%)    		 24
    (12 to 1200)
    death from coronary heart disease 6 years 39
    (8.90%)    		 74
    (16.1%)    		 -80%
    (-160% to -25%)    		 -7.15%
    (-11.4% to -2.87%)    		 -14
    (-35 to -9)

    alpha-tocopherol and beta-carotene v. placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    non-fatal myocardial infarction 6 years 55
    (12.6%)    		 56
    (11.3%)    		 10%
    (-27% to 37%)    		 1.29%
    (-2.88% to 5.46%)    		 78
    (NNT = 35 to infinity;
    NNH = 18 to infinity)
    death from coronary heart disease 6 years 39
    (8.60%)    		 67
    (13.5%)    		 -51%
    (-120% to -4%)    		 -4.58%
    (-8.59% to -0.56%)    		 -22
    (-180 to -12)

    alpha-tocopherol v. placebo
    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    non-fatal myocardial infarction 6 years 55
    (12.6%)    		 40
    (8.58%)    		 32%
    (-1% to 54%)    		 3.97%
    (-0.039% to 7.99%)    		 25
    (NNT = 2600 to infinity;
    NNH = 13 to infinity)
    death from coronary heart disease 6 years 39
    (8.90%)    		 54
    (11.6%)    		 -30%
    (-92% to 12%)    		 -2.68%
    (-6.63% to 1.26%)    		 -37
    (NNT = 15 to infinity;
    NNH = 79 to infinity)

    Comments

    1. Patients were randomised in blocks of eight.

    Citation

    1. Rapola JM, Virtamo J, Ripatti S, et al: Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 1997; 349: 1715-1720
    Contributor: Chris Ball and Clare Wotton, February 2000
    Reviewer:

    Clinical Question.
    Patient previous myocardial infarction
    Intervention or Exposure alpha-tocopherol or beta-carotene
    Comparison placebo
    Outcome death from coronary heart disease, non-fatal myocardial infarction