Stroke: low-dose acetylsalicylic acid decreased stroke, MI and death.

Clinical bottom line (level 1b)

  1. Patients about to undergo carotid endarterectomy who were given low-dose acetylsalicylic acid, were less likely to have any stroke, MI or die, than those given high-dose acetylsalicylic acid (NNT = 47 at 3 months) .
  2. Patients given low-dose acetylsalicylic acid were less likely to have a stroke than those given high-dose (NNT = 46 at 3 months) .
  3. Patients given low-dose were less likely to have a myocardial infarction (NNT = 75 at 3 months) .
  4. There is no clear difference in death from any cause.
Taylor et al: Lancet 1999; 353: 2179-2184
Expires November 2002

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: 74 centres, 48 in the USA, 19 in Canada, 4 in Australia, 1 in Italy, 1 in Argentina and 1 in Finland. (Centres required death&stroke rates of <6% within 30d of operation.)

2849 patients (aged median 69 years, 70% male) scheduled for endarterectomy for arteriosclerotic disease

Excluded if
  • participation in another trial
  • taking acetylsalicylic acid or any other antiplatelet medication that could not be stopped
  • had a recent disabling stroke
  • undergone cardiac surgery in the previous 30 days or were scheduled for cardiac surgery in the next 30 days
  • did not provide informed consent


    • Note:
  • 45 patients were excluded post-randomisation, as surgery was cancelled. There is no information on their distribution across the groups.


    • Control Group: (n = 1409, 1409 analysed): high-dose acetylsalicylic acid - 650 mg or 1300 mg daily
    Experimental Group: (n = 1395, 1395 analysed): low-dose acetylsalicylic acid 81 mg or 325 mg daily
    Randomisation was into 4 groups, but no differences identified between the two lowest and highest doses, therefore they have been collapsed for analysis.
    100% followed for 3 months
    Outcome notes:
    • any stroke : mild, moderate, disabling or fatal
    • any MI : fatal or non-fatal

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    combined endpoint of any stroke MI or death 3 months 118
    (8.37%)    		 87
    (6.24%)    		 26.0%
    (3.00% to 43.0%)    		 2.14%
    (0.21% to 4.06%)    		 47
    (25 to 467)
    any stroke 3 months 95
    (6.74%)    		 64
    (4.59%)    		 32.0%
    (7.00% to 50.0%)    		 2.15%
    (0.45% to 3.86%)    		 46
    (26 to 224)
    any MI 3 months 35
    (2.48%)    		 16
    (1.15%)    		 54.0%
    (17.0% to 74.0%)    		 1.34%
    (0.35% to 2.32%)    		 75
    (43 to 285)
    death from any cause 3 months 30
    (2.13%)    		 27
    (1.94%)    		 9.00%
    (-52.0% to 46.0%)    		 0.19%
    (-0.85% to 1.24%)    		 516
    (NNT = 81 to infinity;
    NNH = 118 to infinity)

    Comments

    1. The exclusion of patients who did not undergo surgery may be enough to unbalance the randomisation and produce this beneficial result. (It is unlikely to overbalance the data to produce the opposite result.)
    2. As the trial did not include a placebo group, the benefit of low-dose acetylsalicylic acid may be underestimated. However, if high-dose acetylsalicylic acid increases the rate of stroke, MI and death (very unlikely), then the benefit of low-dose may be overestimated.
    3. Results such as these need cautious interpretation and application to individual patients may be appropriate in a 30-day window reported herein may not be true in the long term.

    Citation

    1. Taylor DW, Barnett HJM, Haynes RB, et al: Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. Lancet 1999; 353: 2179-2184
    Contributor: Clare Wotton and Bob Phillips, November 1999
    Reviewer: James Toole

    Clinical Question.
    Patient stroke
    Intervention or Exposure low-dose acetylsalicylic acid
    Comparison high-dose acetylsalicylic acid
    Outcome risk of stroke, myocardial infarction or death