Ticlopidine is a
thienopyridine derivative which reduces the risk of reversible ischaemia and
stroke in patients who have previously experienced a cerebral ischaemic episode. In comparison with
aspirin,
ticlopidine produced a significant reduction in the risk of
stroke in a multicentre clinical trial involving more than 3000 patients with previous transient or persistent minor ischaemia, and was superior to placebo for the prevention of
stroke recurrence in more than 1000 patients who had experienced a major
thrombotic stroke. The cost-utility ratio for
ticlopidine in comparison with
aspirin was estimated to be $US31 200 to 55,000 per quality-adjusted life-year gained. Diarrhoea is the most common adverse event in
ticlopidine recipients (20 to 22% incidence versus about 10% with placebo), although
skin rash,
nausea,
dyspepsia,
bleeding events, abnormal liver function and haematological disturbances were also observed in clinical trials. Severe
neutropenia is the most serious event: this developed in 0.85% of patients receiving
ticlopidine in 2 large clinical studies (n = 4098) but resolved
after treatment withdrawal. Fatal
neutropenia, although rare, has been reported in some patients receiving
ticlopidine. Thus,
ticlopidine is effective in reducing the risk of recurrent cerebral ischaemia and
stroke. It appears to provide a gain over
aspirin for the prevention of
stroke after reversible ischaemia, particularly during the first year of treatment (when the risk of
stroke is greatest), although further data on its absolute relative benefit would be useful. The extent to which
ticlopidine is prescribed will probably depend on individual clinicians' perception of its risk/benefit and cost-effectiveness profiles.
Ticlopidine is likely to be particularly useful for
stroke prophylaxis in patients who do not tolerate
aspirin or who have an ischaemic episode during
aspirin treatment, and for the prevention of
stroke recurrence in patients who have previously experienced a major
stroke.