A critical appraisal of ticlopidine, a new antiplatelet agent. Effectiveness and clinical indications for prophylaxis of atherosclerotic events
R. B. Haynes, R. S. Sandler, E. B. Larson, J. L. Pater and F. M. Yatsu
Department of Clinical Epidemiology, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada.
BACKGROUND--Recommendations are broadening for the prophylaxis of
atherosclerotic disorders, but aspirin is the only widely used agent.
Ticlopidine hydrochloride, a new antiplatelet medication, has recently been
approved for prescription in North America. We reviewed the major clinical
trials of ticlopidine and derived guidelines for its use. METHODS--Studies
of ticlopidine were sought through MEDLINE for 1980 to 1990 and through
bibliographies of retrieved articles. All published, randomized trials of
ticlopidine were appraised if they reported major morbidity and mortality
as primary end points. All eligible studies were formally reviewed by an
expert panel according to published principles for critical appraisal of
the medical literature. Both benefits and risks were quantified.
RESULTS--Four randomized trials reported major clinical end points. In
these, ticlopidine was more effective than placebo for preventing
recurrences after completed stroke; was more effective than aspirin for
patients with transient ischemic attacks and partial strokes; and reduced
vascular death and nonfatal myocardial infarction in an open trial among
patients with unstable angina. For patients with intermittent claudication
ticlopidine, was not significantly better than placebo for preventing
myocardial infarction or stroke. Side effects were more common with
ticlopidine than with aspirin or placebo. CONCLUSIONS--Ticlopidine should
be prescribed in place of aspirin for stroke prophylaxis or unstable angina
if the patient is unable to tolerate aspirin. Ticlopidine may also benefit
patients who experience new ischemic events while taking aspirin or,
probably, patients with peripheral vascular disease. A complete blood cell
count should be performed every 2 weeks during the first 3 months of
therapy to check for leukopenia.
