Antiplatelet Treatment with Ticlopidine in Unstable Angina (Studio della Ticlopidine nell'Angina Instabile) - STAI
STAI was a multicenter randomized controlled trial evaluating safety and efficacy of ticlopidine in patients with unstable angina.
Compared to conventional therapy alone, addition of ticlopidine for 6 months to conventional treatment in patients with unstable angina will be associated with a reduction in a risk of myocardial infarction or death from vascular causes.
Patients Screened: 2438
Patients Enrolled: 652
Mean Follow Up: 6 months
Mean Patient Age: 60.1±8.8 years
age not more than 75 years
current therapy with antiplatelet agent
class IV CHF
renal or hepatic failure
peptic ulcer disease, or ongoing gastrointestinal bleeding
Fatal or nonfatal MI and vascular death
TIA, nonfatal stroke, peripheral arterial occlusion
Patients with unstable angina were enrolled within 48 hours of presentation, and were randomly assigned to receive ticlopidine 250 mg twice daily in addition to the conventional treatment (beta-blockers, calcium antagonists, and nitrates), or to continue conventional treatment alone.
Patients continued their assigned treatment following discharge, and had clinical checkups 1, 2, 3, and 6 months after enrollment. No other drugs that can affect platelet function were allowed
Clinical events were evaluated under blinded conditions.
Beta-blockers, calcium channel blockers, nitrates.
Therapy with aspirin was not allowed.
A total of 652 patients were enrolled (338 patients in conventinal therapy group, 314 patients in ticlopidine group). Most patients (75%) had rest angina, with 25% having worsening exertional angina. The rate of withdrawal from the trial prior to the completion of 6 months of therapy was 17.5%.
Using the intention-to-treat analysis, the incidence of primary endpoints was 13.6% in the conventional therapy group, and 7.3% in the ticlopidine group, a 46.3% relative risk reduction (p=0.009). Ticlopidine was associated with a trend towards lower risk of death from myocardial MI or other vascular causes (a decrease of 46.8%, p=0.139), and with a statistically significant decrease in the risk of nonfatal MI (a reduction of 46.1%, p=0.039).
A total of 5 secondary endpoints were observed, all of them in the conventional treatment group.
Ticlopidine was associated with a 5.1% risk of gastrointestinal side effects (nausea, vomiting, diarrhea) and a 1.9% risk of skin reactions. No clinically-significant changes in hematologic parameters, including neutropenia, were observed.
Addition of ticlopidine to conventional treatment for unstable angina was associated with a reduction in a risk of MI or vascular death. This was a valuable early study, confirming efficacy of platelet inhibition in acute coronary syndromes. Its application to modern therapy of ACS is limited by a very low incidence of percutaneous or surgical revascularization in the study population (8% total), infrequent use of beta blockers, and prohibition of aspirin use. The study also pre-dates clinical use of glycoprotein IIb/IIIa inhibitors.
Balsano F, Rizzon P, Violi F, Scrutinio D, et al. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group. Circulation. 1990 82(1):17-26.
Keywords: Neutropenia, Risk, Nausea, Myocardial Infarction, Vomiting, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Diarrhea, Ticlopidine, Blood Platelets, Nitrates, Intention to Treat Analysis, Platelet Glycoprotein GPIIb-IIIa Complex
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