John Olson, MD

BACKGROUND: Guidelines for management of patients after acute myocardial infarction (AMI) recommend daily aspirin therapy.¹ Although ticlopidine reduces the incidence of vascular death, MI, and stroke among people with atherosclerotic disease,² it has not been compared directly with aspirin in the post-AMI period. This study compares the efficacy and safety of aspirin and ticlopidine in survivors of AMI treated with a thrombolytic agent.

POPULATION STUDIED: This multicenter trial enrolled 1470 patients recruited at the time of discharge from the hospital after receiving successful treatment for AMI with a thrombolytic agent. Patients were not included if they required anticoagulation with warfarin, were scheduled for major surgery, had uncontrolled hypertension, or had severe comorbidity likely to limit their life expectancy. The 2 groups were similar with regard to major coronary artery disease risk factors (eg, hypertension, diabetes, smoking) as well as characteristics and management of the incident MI (eg, infarct location, ejection fraction, medications at discharge).

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded multicenter trial. The patients were randomized at hospital discharge to receive either aspirin (80 mg twice daily) or ticlopidine (250 mg twice daily). Clinical follow-up was at 45 days, 3 months, and 6 months after enrollment. During these visits, compliance was assessed and information was collected on outcome endpoints, adverse reactions, and concomitant medications. An intention-to-treat analysis was performed, and patients were followed up for 6 months regardless of whether they were still taking the study drug. The study was large enough to detect a 5% difference in primary endpoints with 95% power. The main limitations in this study were the short follow-up period (6 months) and the relatively low event rate (10%). Compliance and follow-up appear to be good.

OUTCOMES MEASURED: The primary endpoint was the first occurrence of any of the following during the 6 month follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death, or death due to any cause. The study was not large enough to detect differences for specific endpoints, only in the total frequency of endpoints.

RESULTS: At the end of the 6-month follow-up, equal numbers of patients experienced at least 1 primary endpoint (8.0% in each group). Fewer patients taking ticlopidine suffered a repeat nonfatal MI: 8 in the ticlopidine group versus 18 in the aspirin group (1.1% vs 2.4%; P=.049). There were no differences between the groups in frequencies of cardiovascular death, nonvascular death, nonfatal stroke, and documented angina. Seventy-two patients taking aspirin and 90 patients taking ticlopidine reported at least 1 drug-related adverse effect (9.8% vs 12.3%). Serious adverse effects occurred in 11 patients taking aspirin and 18 taking ticlopidine (1.5% vs 2.4%). Thirty-five patients in the aspirin group and 53 in the ticlopidine group stopped treatment because of adverse events. Gastrointestinal symptoms were the most common adverse reactions in both study groups.

BACKGROUND: Guidelines for management of patients after acute myocardial infarction (AMI) recommend daily aspirin therapy.¹ Although ticlopidine reduces the incidence of vascular death, MI, and stroke among people with atherosclerotic disease,² it has not been compared directly with aspirin in the post-AMI period. This study compares the efficacy and safety of aspirin and ticlopidine in survivors of AMI treated with a thrombolytic agent.

POPULATION STUDIED: This multicenter trial enrolled 1470 patients recruited at the time of discharge from the hospital after receiving successful treatment for AMI with a thrombolytic agent. Patients were not included if they required anticoagulation with warfarin, were scheduled for major surgery, had uncontrolled hypertension, or had severe comorbidity likely to limit their life expectancy. The 2 groups were similar with regard to major coronary artery disease risk factors (eg, hypertension, diabetes, smoking) as well as characteristics and management of the incident MI (eg, infarct location, ejection fraction, medications at discharge).

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded multicenter trial. The patients were randomized at hospital discharge to receive either aspirin (80 mg twice daily) or ticlopidine (250 mg twice daily). Clinical follow-up was at 45 days, 3 months, and 6 months after enrollment. During these visits, compliance was assessed and information was collected on outcome endpoints, adverse reactions, and concomitant medications. An intention-to-treat analysis was performed, and patients were followed up for 6 months regardless of whether they were still taking the study drug. The study was large enough to detect a 5% difference in primary endpoints with 95% power. The main limitations in this study were the short follow-up period (6 months) and the relatively low event rate (10%). Compliance and follow-up appear to be good.

OUTCOMES MEASURED: The primary endpoint was the first occurrence of any of the following during the 6 month follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death, or death due to any cause. The study was not large enough to detect differences for specific endpoints, only in the total frequency of endpoints.

RESULTS: At the end of the 6-month follow-up, equal numbers of patients experienced at least 1 primary endpoint (8.0% in each group). Fewer patients taking ticlopidine suffered a repeat nonfatal MI: 8 in the ticlopidine group versus 18 in the aspirin group (1.1% vs 2.4%; P=.049). There were no differences between the groups in frequencies of cardiovascular death, nonvascular death, nonfatal stroke, and documented angina. Seventy-two patients taking aspirin and 90 patients taking ticlopidine reported at least 1 drug-related adverse effect (9.8% vs 12.3%). Serious adverse effects occurred in 11 patients taking aspirin and 18 taking ticlopidine (1.5% vs 2.4%). Thirty-five patients in the aspirin group and 53 in the ticlopidine group stopped treatment because of adverse events. Gastrointestinal symptoms were the most common adverse reactions in both study groups.

BACKGROUND: Guidelines for management of patients after acute myocardial infarction (AMI) recommend daily aspirin therapy.¹ Although ticlopidine reduces the incidence of vascular death, MI, and stroke among people with atherosclerotic disease,² it has not been compared directly with aspirin in the post-AMI period. This study compares the efficacy and safety of aspirin and ticlopidine in survivors of AMI treated with a thrombolytic agent.

POPULATION STUDIED: This multicenter trial enrolled 1470 patients recruited at the time of discharge from the hospital after receiving successful treatment for AMI with a thrombolytic agent. Patients were not included if they required anticoagulation with warfarin, were scheduled for major surgery, had uncontrolled hypertension, or had severe comorbidity likely to limit their life expectancy. The 2 groups were similar with regard to major coronary artery disease risk factors (eg, hypertension, diabetes, smoking) as well as characteristics and management of the incident MI (eg, infarct location, ejection fraction, medications at discharge).

STUDY DESIGN AND VALIDITY: This was a randomized double-blinded multicenter trial. The patients were randomized at hospital discharge to receive either aspirin (80 mg twice daily) or ticlopidine (250 mg twice daily). Clinical follow-up was at 45 days, 3 months, and 6 months after enrollment. During these visits, compliance was assessed and information was collected on outcome endpoints, adverse reactions, and concomitant medications. An intention-to-treat analysis was performed, and patients were followed up for 6 months regardless of whether they were still taking the study drug. The study was large enough to detect a 5% difference in primary endpoints with 95% power. The main limitations in this study were the short follow-up period (6 months) and the relatively low event rate (10%). Compliance and follow-up appear to be good.

OUTCOMES MEASURED: The primary endpoint was the first occurrence of any of the following during the 6 month follow-up: fatal and nonfatal MI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death, or death due to any cause. The study was not large enough to detect differences for specific endpoints, only in the total frequency of endpoints.

RESULTS: At the end of the 6-month follow-up, equal numbers of patients experienced at least 1 primary endpoint (8.0% in each group). Fewer patients taking ticlopidine suffered a repeat nonfatal MI: 8 in the ticlopidine group versus 18 in the aspirin group (1.1% vs 2.4%; P=.049). There were no differences between the groups in frequencies of cardiovascular death, nonvascular death, nonfatal stroke, and documented angina. Seventy-two patients taking aspirin and 90 patients taking ticlopidine reported at least 1 drug-related adverse effect (9.8% vs 12.3%). Serious adverse effects occurred in 11 patients taking aspirin and 18 taking ticlopidine (1.5% vs 2.4%). Thirty-five patients in the aspirin group and 53 in the ticlopidine group stopped treatment because of adverse events. Gastrointestinal symptoms were the most common adverse reactions in both study groups.