Ticlopidine versus aspirin after myocardial infarction (STAMI) trial. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial). A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. Low-dose aspirin combined with dipyridamole versus anticoagulants after femoropopliteal percutaneous transluminal angioplasty. Antiplatelet agents in thrombotic thrombocytopenic purpura (TTP). Results of a randomized multicenter trial by the Italian Cooperative Group for TTP. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study.
We sought to compare the efficacy of aspirin and ticlopidine in survivors of acute myocardial infarction (AMI) treated with thrombolysis.
                The role of ticlopidine in secondary prevention after AMI has not yet been explored.
                Of 4,696 patients with AMI treated with thrombolysis who were screened, 261 died in the hospital (5.6%) and 1,470 were enrolled in this randomized, double-blind, multicenter trial and allocated to treatment with either aspirin (160 mg/day) or ticlopidine (500 mg/day). The most frequent reasons for exclusion were refusal to give informed consent, planned myocardial revascularization, risk of noncompliance with study procedures, need for anticoagulant therapy and contraindications to the study treatments. The primary end point was the first occurrence of any of the following events during the six-month follow-up: fatal and nonfatal AMI, fatal and nonfatal stroke, angina with objective evidence of myocardial ischemia, vascular death or death due to any other cause.
                The primary end point was recorded in 59 (8.0%) of the 736 aspirin-treated and 59 (8.0%) of the 734 ticlopidine-treated patients (p = 0.966). Vascular death was the first event in five patients taking aspirin and in six patients taking ticlopidine (0.7% vs. 0.8%; p = NS); nonfatal AMI in 18 and 8 (2.4% vs. 1.1%; p = 0.049); nonfatal stroke in 3 and 4 (0.4% vs. 0.5%; p = NS); and angina in 33 and 40 (4.5% vs. 5.4%; p = NS), respectively. The frequency of adverse reactions was not significantly different between the two groups.
                No difference was found between the ticlopidine and aspirin groups in the rate of the primary combined end point of death, recurrent AMI, stroke and angina. Antithrombotic drugs are used after coronary-artery stenting to prevent stent thrombosis. We compared the efficacy and safety of three antithrombotic-drug regimens - aspirin alone, aspirin and warfarin, and aspirin and ticlopidine - after coronary stenting.
                Of 1965 patients who underwent coronary stenting at 50 centers, 1653 (84.1 percent) met angiographic criteria for successful placement of the stent and were randomly assigned to one of three regimens: aspirin alone (557 patients), aspirin and warfarin (550 patients), or aspirin and ticlopidine (546 patients). All clinical events reflecting stent thrombosis were included in the prespecified primary end point: death, revascularization of the target lesion, angiographically evident thrombosis, or myocardial infarction within 30 days.
                The primary end point was observed in 38 patients: 20 (3.6 percent) assigned to receive aspirin alone, 15 (2.7 percent) assigned to receive aspirin and warfarin, and 3 (0.5 percent) assigned to receive aspirin and ticlopidine (P=0.001 for the comparison of all three groups). Hemorrhagic complications occurred in 10 patients (1.8 percent) who received aspirin alone, 34 (6.2 percent) who received aspirin and warfarin, and 30 (5.5 percent) who received aspirin and ticlopidine (P<0.001 for the comparison of all three groups); the incidence of vascular surgical complications was 0.4 percent (2 patients), 2.0 percent (11 patients), and 2.0 percent (11 patients), respectively (P=0.01). There were no significant differences in the incidence of neutropenia or thrombocytopenia (overall incidence, 0.3 percent) among the three treatment groups.
                As compared with aspirin alone and a combination of aspirin and warfarin, treatment with aspirin and ticlopidine resulted in a lower rate of stent thrombosis, although there were more hemorrhagic complications than with aspirin alone. After coronary stenting, aspirin and ticlopidine should be considered for the prevention of the serious complication of stent thrombosis. The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release.
                No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel.
                After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h.
                A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05).
                Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population. We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater. Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated.
                Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization.
                In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001).
                Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation. Blacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke.
                To determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients.
                Randomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years.
                A total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin.
                Recurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke.
                The blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P =.12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P =.08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P =.12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P =.69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis.
                During a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke. To investigate whether anticoagulation or platelet inhibition treatment provides better prevention of reobstruction after percutaneous transluminal angioplasty (PTA).
                In a controlled study, 160 patients received either oral anticoagulants or a combination of low-dose acetylsalicylic acid (25 mg) and dipyridamole (200 mg) (ASAD) twice daily for 1 year after successful femoropopliteal PTA. Compliance was comparable. The patients in the two groups had similar clinical and angiographic characteristics. Patency was assessed with noninvasive methods 1 day and then 3, 6, and 12 months after PTA and was confirmed at angiography at the end of the study in 112 patients.
                Patency in patients who received anticoagulants was 53% and was not statistically significantly different from 69% in patients who received ASAD (P = .18). With anticoagulants, there were four bleeding complications (one was fatal); with ASAD, only five minor complications occurred.
                ASAD is at least as effective as anticoagulants for secondary prevention of obstruction after PTA but has less severe side effects. Antiplatelet agents are often included in plasma exchange-based regimens for thrombotic thrombocytopenic purpura (TTP) patients; however, the opportuneness of their use in TTP is still controversial. The italian Cooperative Group for TTP carried out a randomized trial to investigate their actual effectiveness, both in acute TTP and as maintenance treatment.
                Seventy-two TTP patients were randomized to receive plasma exchange and steroids with (group B) or without (group A) aspirin and dipyridamole. Treatment efficacy was evaluated after 15 days and salvage treatments were also considered for non-responders. Upon disease remission, the patients already treated with antiplatelet agents received ticlopidine for one year.
                Regarding the treatment of acute phase TTP, similar overall response rates were observed in the two groups (91.4% in group B vs. 75.6% in group A), but lower mortality rates were observed at 15 days in the patients treated with antiplatelet agents; as a matter of fact, 5 patients from arm A died in the first 15 days (13.5%) versus only one in arm B (2.8%). These figures, while not statistically significant, seem to suggest that antiplatelet agents might be useful in preventing deaths in acute TTP; moreover, bleeding did not worsen in antiplatelet agent-treated patients. As for the role of maintenance treatment, our results support the efficacy and safety of one-year ticlopidine therapy since the current relapse rate is significantly higher in non-treated patients; as a matter of fact, 6 patients (21.4%) in the non-ticlopidine group and only 2 (6.25%) in the ticlopidine group relapsed (P = .0182 in favor of maintenance treatment).
                Our results suggest the usefulness of antiplatelet agents in the treatment of acute phase TTP patients. Moreover, one-year ticlopidine maintenance therapy appears to be beneficial in preventing TTP relapses; however, only the completion of an adequate follow-up for all patients will definitively confirm this observation. The Swedish Ticlopidine Multicentre Study (STIMS) was a double-blind placebo-controlled trial designed to determine whether ticlopidine, a platelet antiaggregatory agent, reduces the incidence of myocardial infarction, stroke and transitory ischaemic attacks in patients with intermittent claudication. A total of 687 patients was monitored for a minimum of 5 years or until an end-point was reached. The number of end points (99 vs. 89), analysed according to the intention-to-treat principle, was 11.4% lower in the ticlopidine group (P = 0.24). The mortality rate was 29.1% lower in the ticlopidine group (64 vs. 89, P = 0.015); this observation could be accounted for by a reduced mortality from ischaemic heart disease. On-treatment analysis showed there to be significantly fewer end points in the ticlopidine group (47 vs. 76, P = 0.017). Diarrhoea was the most common side-effect. Reversible leucopenia or thrombocytopenia was reported in seven patients on ticlopidine. It is concluded that the high morbidity and mortality from cardio- and cerebrovascular disease in patients with intermittent claudication can be reduced by long-term treatment with ticlopidine.
Ticlopidine plus aspirin after coronary stenting is effective in reducing the risk of the revascularization, non fatal myocardial infarction and bleeding complications when compared with oral anticoagulants. No effect is observed on total mortality. However, the haematological side effects of ticlopidine are still a matter of concern, and strict monitoring of blood-cell counts is recommended. Physicians should also be aware of the possibility of rare although potentially life-threatening complications such as TTP