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Prevention of Myocardial Infarction and Stroke in Patients With Intermittent Claudication - STIMS
Description:
STIMS was a randomized, double-blind trial assessing efficacy of ticlopidine compared to placebo in preventing myocardial infarction (MI) or stroke among patients with intermittent claudication.
Hypothesis:
Therapy with ticlopidine will be associated with a lower incidence of MI, stroke, or transient ischemic attack (TIA).
Study Design
Study Design:
Patients Enrolled: 687
Mean Follow Up: 5.6 years
Mean Patient Age: Mean age 60 years
Female: 24
Patient Populations:
Age 18-70 years, and intermittent claudication (peripheral arterial disease confirmed by an abnormal ankle-brachial index)
Exclusions:
Age >70 years, pregnant women, therapy with other antiplatelet agents, therapy with lipid-lowering therapy other than clofibrate, MI in the preceding three months, surgery in the preceding one month, insulin-requiring diabetes, renal failure or hepatic dysfunction, or uncontrolled hypertension
Primary Endpoints:
Acute MI, stroke, or TIA
Drug/Procedures Used:
Subjects were enrolled in the study if they had a history of intermittent claudication. Subjects were randomly assigned to receive ticlopidine 250 mg twice daily, or matching placebo.
Concomitant therapy for hypertension was continued at the discretion of the treating physician. Hyperlipidemia was controlled by diet and/or clofibrate. Patients were advised not to use aspirin.
Patients were monitored for a minimum of five years, or until an endpoint was reached.
Concomitant Medications:
If needed: beta-blockers, calcium antagonists, diuretics, clofibrate, and oral hypoglycemics
Principal Findings:
A total of 687 subjects were enrolled (ticlopidine, 346; placebo, 341). The two treatment groups were well matched for all baseline characteristics and cardiovascular risk factors. Median duration of follow-up was 5.6 years. A total of 266 subjects (ticlopidine, 120; placebo, 144) completed the study, and 34.6% of the subjects were still taking medication at the end of the study.
By intention-to-treat analysis, therapy with ticlopidine compared to placebo was associated with a trend toward reduction in the incidence of the primary endpoint of MI, stroke, or TIA (25.7% vs. 29.0%, respectively; relative risk reduction of 11.4%, p=0.24). The number of cases with fatal MI was lower in the ticlopidine group (15 vs. 26 for placebo).
With the on-treatment evaluation, therapy with ticlopidine compared to placebo was associated with a significant reduction in the incidence of the primary endpoints (13.8% vs. 22.4%; relative risk reduction of 38.4%, p=0.017). Total mortality was lower in the ticlopidine group than in the placebo group (18.5% vs. 26.1%, p=0.015).
Therapy with ticlopidine was associated with more adverse effects than placebo. Diarrhea was the most prevalent side effect (ticlopidine, 22% vs. placebo, 9%). Seven patients (2%) in the ticlopidine group experienced hematologic adverse effects versus none in the placebo group.
Interpretation:
Long-term administration of ticlopidine to patients with lower extremity arterial occlusive disease was associated with a reduction in the incidence of MI and stroke. These data further extend the observations of CATS and TASS trials, and provide a useful background for the subsequent, much larger CAPRIE trial, that used a later-generation antiplatelet agent, clopidogrel.
References:
Janzon L, Bergqvist D, Boberg J, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. J Intern Med 1990;227:301-8.
Keywords: Intermittent Claudication, Myocardial Infarction, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Platelet Aggregation Inhibitors, Hyperlipidemias, Ankle Brachial Index, Diarrhea, Diuretics, Peripheral Arterial Disease, Ticlopidine, Risk Factors, Lower Extremity, Clofibrate, Hypoglycemic Agents, Diet, Hypertension
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