Antiplatelet Treatment with Ticlopidine in Unstable Angina (Studio della Ticlopidine nell'Angina Instabile) - STAI

Description:

STAI was a multicenter randomized controlled trial evaluating safety and efficacy of ticlopidine in patients with unstable angina.

Hypothesis:

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.

Study Design

Study Design:

Patients Screened: 2438
Patients Enrolled: 652
Mean Follow Up: 6 months
Mean Patient Age: 60.1±8.8 years
Female: 28%

Patient Populations:

unstable angina
age not more than 75 years

Exclusions:

ST-elevation MI
current therapy with antiplatelet agent
Prinzmetal's angina
prior CABG
class IV CHF
severe hypertension
renal or hepatic failure
peptic ulcer disease, or ongoing gastrointestinal bleeding

Primary Endpoints:

Fatal or nonfatal MI and vascular death

Secondary Endpoints:

TIA, nonfatal stroke, peripheral arterial occlusion

Drug/Procedures Used:

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.

Concomitant Medications:

Beta-blockers, calcium channel blockers, nitrates.
Therapy with aspirin was not allowed.

Principal Findings:

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.

Interpretation:

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.

References:

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.

Clinical Topics: Acute Coronary Syndromes

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


< Back to Listings