Stroke: ticlopidine decreased the risk of stroke.

Clinical bottom line (level 1b)

  1. Patients at high-risk of a stroke who were given ticlopidine were less likely to have any stroke, than those given aspirin (NNT = 40 at 3 years) .
  2. Patients who are given ticlopidine, had no clear difference in death from any cause, fatal or nonfatal stroke independently, or death and stroke together, than those given aspirin.
  3. Patients given ticlopidine were more likely to have an adverse effect (NNH = 11 at 3 years) which may be serious (e.g. neutropenia).
Hass et al: New England Journal of Medicine 1989; 321: 501-507
Expires March 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 56 centres, North America

3069 patients (aged range 39 to 94 years; mean 63, 65% male) transient ischaemic attack (focal ischaemic cerebrvascular event lasting <24 hours and followed by complete recovery), amaurosis fugax (unilateral ischaemic retinal episode lasting <24 hours), reversible ischaemic neurologic deficit (focal ischaemic cerebrovascular event lasting >24 hours but <3 weeks and followed by complete recovery) or minor stroke ( event resulting in minimal permanent neurologic deficit and at least 80% recovery of function within 3 weeks) during the three months before study entry.

Excluded if
  • <40 years old
  • women with childbearing potential
  • symptoms due to migraine, cardiogenic embolism or haemotologic disorders
  • history of peptic ulcer disease, upper gastrointestinal bleeding or life-threatening disease such as cancer
  • previous hypersensitivity or intolerance to aspirin or anticoagulants
  • underwent elective carotid endarterectomy


    • Note:
  • Randomisation in each centre was stratified by history of ischaemic cardiovascular disease, occurrence of moderate or major stroke >three months before entry and patient's sex.


    • Control Group: (n = 1540, 1531 analysed): aspirin 650 mg twice daily
    Experimental Group: (n = 1529, 1526 analysed): ticlopidine hydrochloride 250 mg twice daily
    All known platelet antiaggregants and anticoagulants were prohibited. Acetominophen was used as an alternative analgesic. In cases of elective surgery, the study drug was stopped one week before the operation and resumed after it.
    97% followed for 3 years

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    any stroke 3 years 212
    (13.8%)    		 172
    (11.3%)    		 18.0%
    (1.00% to 32.0%)    		 2.52%
    (0.18% to 4.86%)    		 40
    (21 to 561)
    any adverse experience 3 years 813
    (52.8%)    		 945
    (61.8%)    		 -17.0%
    (-10.0% to -24.0%)    		 -9.01%
    (-12.5% to -5.53%)    		 -11
    (-18 to -8)
    death from all causes or nonfatal stroke 3 years 349
    (22.7%)    		 306
    (20.0%)    		 12.0%
    (-1.00% to 23.0%)    		 2.65%
    (-0.25% to 5.55%)    		 38
    (NNT = 403 to infinity;
    NNH = 18 to infinity)
    nonfatal stroke 3 years 189
    (12.3%)    		 156
    (10.2%)    		 17.0%
    (-2.00% to 32.0%)    		 2.07%
    (-0.16% to 4.30%)    		 48
    (NNT = 612 to infinity;
    NNH = 23 to infinity)
    fatal stroke 3 years 23
    (1.49%)    		 16
    (1.05%)    		 30.0%
    (-32.0% to 63.0%)    		 0.45%
    (-0.34% to 1.24%)    		 224
    (NNT = 290 to infinity;
    NNH = 81 to infinity)
    death from other cause 3 years 137
    (8.90%)    		 134
    (8.76%)    		 1.00%
    (-24.0% to 22.0%)    		 0.13%
    (-1.88% to 2.14%)    		 756
    (NNT = 53 to infinity;
    NNH = 47 to infinity)

    Comments

    1. The cost of monitoring and of the drug, along with these side effects limit its use to those at risk of recurrent stroke and can not tolerate other agents
    2. 89% of patients took at least three quarters of the medication prescribed more than 90% of the time. 13 patients in the aspirin group and 11 in the ticlopidine group never took their drug.

    Citation

    1. Hass WK, Easton JD, Adams HP, et al: A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. New England Journal of Medicine 1989; 321: 501-507
    Contributor: Clare Wotton and Musab Hayatli, December 1999
    Reviewer: Daniel Sontheimer

    Clinical Question.
    Patient transient or mild persistent focal cerebral or retinal ischaemia
    Intervention or Exposure ticlopidine hydrochloride
    Comparison aspirin
    Outcome stroke or death