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PubMed1999

Effects of ticlopidine or ticlopidine plus aspirin on platelet aggregation and ATP release in normal volunteers: why aspirin improves ticlopidine antiplatelet activity.

Aspirin and ticlopidine are used to prevent arterial thrombosis. In some clinical settings ticlopidine is administered with aspirin for improving antithrombotic effect. We administered aspirin (100 mg/day), ticlopidine (500 mg/day), or ticlopidine and aspirin for 7 days to healthy volunteers. Platelet aggregation and ATP release induced by sodium arachidonate, ADP, or a combination of both were measured. Sodium arachidonate (0.25 mmol/L), which produces no platelet aggregation, combined with adenosine diphosphate (1 mumol/L), which produced a reversible platelet aggregation of 20% after ticlopidine, resulted in a synergistic platelet aggregation response in normal (74.6 +/- 9.2%) and in ticlopidine platelet-rich plasma (59.1% +/- 14.9%, p < 0.0001). Synergism after sodium arachidonate (0.75 mmol/L) plus adenosine diphosphate (4 mumol/L) fell from 75.8% +/- 11.0% and 59.1% +/- 15.6% after ticlopidine or aspirin, respectively, to 14.8% +/- 18.0% (p < 0.0001) after ticlopidine plus aspirin. Aspirin and ticlopidine alone did not inhibit adenosine triphosphate release as thoroughly as did aspirin plus ticlopidine. Aspirin or ticlopidine does not adequately prevent platelet activity as ticlopidine plus aspirin do. Addition of aspirin to treatment with ticlopidine improves their antiplatelet activity and better results could be obtained in arterial thrombotic prevention strategies.

Adenosine Triphosphate↗
PubMed2000

Abciximab, ticlopidine, and concomitant abciximab-ticlopidine therapy: ex vivo platelet aggregation inhibition profiles in patients undergoing percutaneous coronary interventions.

BACKGROUND: We examined the ex vivo platelet aggregation profiles of patients who underwent percutaneous coronary intervention and received either abciximab, ticlopidine, or both agents. STUDY DESIGN AND METHODS: The trial was a prospective, nonrandomized, single-center, open-label study of 42 patients undergoing percutaneous coronary intervention who received the following regimens: group 1, abciximab (0.25 mg/kg bolus and 12-hour, 0.125 microg/kg per minute infusion); group 2, ticlopidine (250 mg twice daily for 14 consecutive days, initiated 12 to 18 hours before intervention); group 3, abciximab plus ticlopidine initiated 12 to 18 hours before procedure; and group 4, abciximab plus ticlopidine initiated 72 to 96 hours before procedure. Platelet aggregation measurements to adenosine diphosphate (ADP) and a thrombin receptor activating peptide (TRAP, 8 micromol/L) were obtained before ticlopidine treatment, after initiation of ticlopidine, and immediately before abciximab treatment and intervention, then at several time periods after onset of abciximab treatment. Platelet surface abciximab levels were monitored by flow cytometry. RESULTS: Neither ticlopidine regimen resulted in appreciable platelet inhibition before intervention and before administration of abciximab. In the ticlopidine-only arm, suppression of platelet aggregation to the weakest stimuli (5 micromol/L ADP; 23% +/- 7.5%) was detected within 24 hours after intervention, with maximal inhibition to both 5 and 20 micromol/L ADP observed 7 days after intervention (48% +/- 7.9% and 18% +/- 8.7%, respectively). In contrast, ticlopidine marginally suppressed TRAP-mediated platelet activation at times when maximal effects on ADP-mediated platelet aggregation were evident. Neither ticlopidine regimen appreciably enhanced platelet inhibition during or shortly after cessation of abciximab treatment. For all 3 abciximab treatment arms, profound inhibition of ADP-induced (>80%) and TRAP-induced (>65%) platelet aggregation was observed 2 hours after treatment. In the abciximab-only arm, platelet aggregation responses gradually recovered, with the rate of response directly proportional to the strength of stimuli. However, in the ticlopidine plus abciximab arms, recovery of platelet aggregation at later times (7 and 14 days) reached a plateau and reflected the extent of inhibition observed in ticlopidine-treated patients. No difference in the clearance of surface-bound abciximab from circulating platelets was observed between the abciximab and abciximab plus ticlopidine arms. CONCLUSIONS: Concomitant abciximab plus ticlopidine treatment yields a platelet inhibition profile that is a composite of the effects of the 2 agents. In the early stages of treatment, inhibition of ex vivo platelet aggregation was mediated primarily by abciximab; effects were more moderate and were predominately mediated by ticlopidine.

Abciximab↗
PubMed2000

Metabolism of ticlopidine by activated neutrophils: implications for ticlopidine-induced agranulocytosis.

Ticlopidine is associated with a relatively high incidence of agranulocytosis and aplastic anemia. We have shown that other drugs associated with agranulocytosis are metabolized to reactive metabolites by activated human neutrophils or by HOCl, which is the major oxidant produced by activated neutrophils. We set out to test the hypothesis that ticlopidine also fits this pattern and is oxidized to a reactive intermediate by activated neutrophils and HOCl. As much as 8% ticlopidine was metabolized by activated human neutrophils to a dehydro-ticlopidine; however, this product did not account for all of the decrease in ticlopidine concentration. The oxidation products of ticlopidine by the combination of myeloperoxidase and hydrogen peroxide were the same as those by HOCl: dehydrogenated ticlopidine and 2-chloroticlopidine. A neutrophil-derived reactive metabolite of ticlopidine was trapped with GSH and the same ticlopidine-GSH conjugate was found in both the myeloperoxidase and HOCl systems. Evidence for the identity of the reactive metabolite was obtained by reaction of ticlopidine with HOCl in a flow reaction system coupled to a mass spectrometer. The mass spectra suggested that the reactive metabolite was a thiophene-S-chloride. We conclude that ticlopidine follows the same pattern of reactive metabolite formation by activated neutrophils as other drugs associated with a high incidence of agranulocytosis, and the putative thiophene-S-chloride formed by activated neutrophils may be responsible for ticlopidine-induced agranulocytosis.

Agranulocytosis↗
PubMed1989

A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group.

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.

Aspirin↗
PubMed1992

Ticlopidine versus aspirin for the prevention of recurrent stroke. Analysis of patients with minor stroke from the Ticlopidine Aspirin Stroke Study.

BACKGROUND AND PURPOSE: Ticlopidine has not been formally compared with aspirin in patients with a completed stroke. We therefore performed an analysis on a subgroup of patients from the Ticlopidine Aspirin Stroke Study (TASS) with a recent minor completed stroke as the qualifying ischemic event. METHODS: This was a multicenter, double-blind, randomized trial of patients with a recent history of cerebral ischemia. Eligible patients had a qualifying minor stroke within 3 months of study entry. All patients received either 650 mg aspirin twice daily or 250 mg ticlopidine twice daily for up to 5.8 years. The primary study end point was the first occurrence of nonfatal stroke or death from any cause. A secondary end point was the first occurrence of a fatal or nonfatal stroke. RESULTS: Minor stroke was the qualifying ischemic event in 927 patients (463 received ticlopidine and 464 received aspirin). The cumulative event rate at 1 year for nonfatal stroke or death was 6.3% for patients receiving ticlopidine and 10.8% for patients receiving aspirin, a 42% risk reduction in favor of ticlopidine. For fatal or nonfatal stroke, the cumulative event rate at 1 year was 4.8% for patients receiving ticlopidine and 7.5% for those receiving aspirin, a risk reduction of 36% for ticlopidine relative to aspirin. The overall risk reductions were 22.1% for nonfatal stroke or death and 19.9% for fatal or nonfatal stroke. Adverse reactions were reported in 58% of the ticlopidine patients and 51% of the aspirin patients. CONCLUSIONS: The results in this subgroup are consistent with the overall TASS results and show that ticlopidine is somewhat more effective than aspirin for reducing the risk of stroke in patients with a completed minor stroke.

Adult↗
PubMed1993

The efficacy and safety of ticlopidine and aspirin in non-whites: analysis of a patient subgroup from the Ticlopidine Aspirin Stroke Study.

We analyzed the efficacy of ticlopidine and aspirin in the non-white subgroup of patients from the Ticlopidine Aspirin Stroke Study. In this double-blind, randomized, multicenter study, patients received either ticlopidine 250 mg (312 non-white patients) or aspirin 650 mg (291 non-white patients) twice a day. The 1-year cumulative event rate per 100 patients for nonfatal stroke or death from any cause was 5.5 for ticlopidine and 10.6 for aspirin--an apparent 48.1% reduction in risk with ticlopidine relative to aspirin. The 1-year cumulative event rate for fatal or non-fatal stroke was 3.7 for ticlopidine and 9.4 for aspirin--an apparent 60.8% reduction in risk with ticlopidine relative to aspirin. The cumulative event rates for both endpoints also were lower in ticlopidine-treated patients after the 2nd and 3rd years. These reductions were not significantly different between treatment groups, but were of the same order of magnitude as previously found for the total series, which did attain statistical significance (p = 0.048), and the frequency of adverse events was not significantly different between the two treatment groups. Severe neutropenia, the most serious adverse event associated with ticlopidine use, did not occur in non-white patients. These results suggest that ticlopidine is superior to aspirin for stroke prevention in non-whites.

Aged↗
PubMed1998

Ticlopidine increases nitric oxide generation in heart-transplant recipients: a possible novel property of ticlopidine.

The objective of this study was to evaluate the effects of ticlopidine on the generation of eicosanoids and nitric oxide in heart-transplant recipients. In a randomized double-blind study, we studied the urinary excretion of the stable metabolites of thromboxane, prostacyclin, and nitric oxide before and after ticlopidine (250 mg/day). Platelet aggregation was significantly reduced in ticlopidine-treated patients [from 40.2 +/- 24.2% of maximal aggregation to 14.7 +/- 8.2% in response to adenosine diphosphate (ADP); p < 0.001] but not in the placebo group, confirming the efficacy of the drug with that dosage in these specific patients. The 24-h urinary excretion of prostacyclin metabolites was not modified by ticlopidine (1,865 +/- 833 ng/24 h at day 14 and 1,664 +/- 425 ng/24 h at day 0), whereas the excretion of thromboxane B2 tended to increase in the ticlopidine group (from 3,854 +/- 1,163 ng/24 h at day 0 to 5,014 +/- 2,914 ng/24 h at day 14), although not significantly. The excretion of nitric oxide metabolites (although not different from that of healthy nonimmunosuppressed subjects) was significantly (p < 0.005) increased in the ticlopidine group (from 3,082 +/- 1,683 micromol/24 h at day 0 to 4,133 +/- 2,262 micromol/24 h at day 14), but not in controls. Thus ticlopidine does not reduce prostacyclin but increases the systemic generation of nitric oxide, both substances having major antiplatelet and vasodilator properties. Further studies are warranted to examine whether ticlopidine could reduce the incidence of thromboembolic complications in these patients and whether this possible novel property of ticlopidine is restricted to immunosuppressed heart-transplant recipients.

Analysis of Variance↗
PubMed2003

Ticlopidine alone versus ticlopidine plus aspirin for preventing recurrent stroke.

OBJECTIVE: To compare the efficacy and safety of two antiplatelet regimens, ticlopidine alone (200 mg daily) and ticlopidine (100 mg daily) plus aspirin (81 mg daily), in patients with ischemic stroke from the Tokai district of Japan. METHODS: A randomized comparative study was performed from April 1992 until December 1995, with follow-up for an average of 1.59 years (maximum: 3 years). Statistical analysis was done on 270 eligible patients (138 treated with ticlopidine alone and 132 treated with ticlopidine plus aspirin). PATIENTS: A total of 276 patients who had cerebral infarction within the previous 1 to 6 months, or one or more transient ischemic attacks within the previous 3 months. RESULTS: The incidence of ischemic and hemorrhagic stroke, myocardial infarction, and other vascular events was 10.1% (n = 14) in the ticlopidine group and 9.8% (n = 13) in the ticlopidine plus aspirin group, showing no significant difference (p = 0.933). There was also no significant difference in the event-free rate between the two groups (p = 0.5003, Kaplan-Meier analysis and log-rank test). Regarding serious adverse reactions, neutropenia occurred in one patient from the ticlopidine group, while gastric ulcer and thrombocytopenia occurred in one patient each from the ticlopidine plus aspirin group. CONCLUSION: We conclude that both antiplatelet regimens are comparable in efficacy and safety for preventing the recurrence of ischemic stroke.

Adult↗
PubMed2001

Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting: follow-up results of a randomized study.

A combined antiplatelet treatment with ticlopidine and aspirin has been accepted as standard pharmacological regimen after coronary artery stenting. No data of a randomized trial are available on ticlopidine monotherapy. This prospective, randomized monocenter trial investigates the role of ticlopidine monotherapy versus combined antiplatelet therapy with ticlopidine and aspirin in unselected patients undergoing coronary artery stenting. After successful placement of 378 coronary artery stents, two hundred and forty-three consecutive patients were randomly assigned to receive antiplatelet therapy with 2 x 250 mg ticlopidine (121 patients) or a combination of 2 x 250 mg ticlopidine plus 100 mg aspirin (122 patients) daily. The primary endpoint included the absence of death, cardiac events and vascular access-site complications during the in-hospital phase. Angiographic and clinical assessment was repeated at the 3-month follow-up exam. Two hundred and thirty-seven patients (97.5%) were free from cardiac and non-cardiac events. Stent thromboses were seen in 2 patients of the combined treatment group, while none were observed in the monotherapy group. No statistically significant differences were found between the 2 groups regarding the primary endpoint. Angiography performed in 210 patients (86.4%) at follow-up revealed a restenosis rate of 29.4% in the combined treatment group and 27.8% in the monotherapy group. Monotherapy with ticlopidine is as safe and effective as a combined regimen of ticlopidine plus aspirin after coronary artery stenting in an unselected patient population. These results need to be confirmed in a larger multicenter trial.

Aged↗
PubMed1990

Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study.

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.

Aged↗
PubMed1993

Efficacy of ticlopidine and aspirin for prevention of reversible cerebrovascular ischemic events. The Ticlopidine Aspirin Stroke Study.

BACKGROUND AND PURPOSE: This subgroup analysis from the Ticlopidine Aspirin Stroke Study (TASS) compared ticlopidine, a new antiplatelet agent, with aspirin for the prevention of recurrent transient ischemic attacks in patients who had a recent reversible cerebrovascular event. METHODS: This was a multicenter, double-blind, randomized trial in patients with a recent cerebral ischemic history. Patients with a reversible cerebral ischemic event within 3 months of enrollment were eligible for the study. All patients received either aspirin 650 mg twice daily or ticlopidine 250 mg twice daily for up to 5.8 years. The primary end point in this analysis was the first occurrence of a reversible ischemic event either alone or combined with nonfatal stroke or death and fatal or nonfatal stroke. RESULTS: Overall, ticlopidine was better than aspirin for reducing the risk of reversible ischemic events either alone or as a composite with death and/or stroke or with fetal and/or nonfatal stroke (P = .007 to P < .001). The risk reductions with ticlopidine were maintained for the duration of the 5-year follow-up. The most frequent or clinically important adverse effects associated with ticlopidine were diarrhea, rash, and neutropenia. Neutropenia was severe in 13 patients but resolved promptly with discontinuation of therapy. CONCLUSIONS: The results in this subgroup of patients with reversible ischemic disease, as well as the overall analysis of TASS, suggest that ticlopidine is a more effective agent than aspirin for the prevention of recurrent transient ischemic attacks.

Adult↗
PubMed1994

Long-term effects of ticlopidine on lower limb blood flow, ankle/brachial index and symptoms in peripheral arteriosclerosis. A double-blind study. The STIMS Group in Lund. Swedish Ticlopidine Multicenter Study.

The aim was to test within a randomized double-blind trial whether the platelet inhibitor ticlopidine might improve peripheral blood flow and distal pressures in patients with aortofemoral arteriosclerosis. One hundred and one patients with intermittent claudication were studied after one year, after two to three years, and after five years of treatment with ticlopidine, 500 mg/day, or placebo. Analysis was performed according to years on treatment. Baseline flow values as assessed by venous occlusion plethysmography were significantly and similarly deranged in the ticlopidine and placebo groups as compared with a reference group of healthy subjects. Ankle/brachial index was unrelated to either leg blood flow variables or walking distance. After five years of treatment (median follow-up time) a slight tendency to a slower progression of disease was observed in the ticlopidine group as compared with placebo. However, intergroup differences were not significant. Therefore, the potential benefit of ticlopidine in this respect is from a clinical point of view certainly only marginal. Minor increases in claudication distances were found with no difference between groups. Smoking habits and lipoproteins were mainly unaltered at the end of the study. It is concluded that platelet inhibition for up to five years has no clear beneficial effect on leg blood flow variables, ankle/brachial index, or walking distances and probably no clinically relevant retarding effect on the slow progression of atherosclerosis. This lack of influence must be distinguished from the antithrombotic effect of ticlopidine, shown as a decreased incidence of acute cardiovascular events and mortality in the authors' multicenter study, STIMS (the Swedish Ticlopidine Multicenter Study).

Adult↗
PubMed1991

Ticlopidine treatment for patients with unstable angina at rest. A further analysis of the study of ticlopidine in unstable angina. Studio della Ticlopidina nell'Angina Instabile Group.

Data collected to investigate the effects of ticlopidine in a subset of 489 patients with angina at rest accompanied by transient ischaemic electrocardiographic changes have been analysed. Of the 489 patients, 255 received conventional treatment including beta-blockers, nitrates, or calcium antagonists (control group); 234 received conventional treatment plus ticlopidine 250 mg b.i.d. (ticlopidine group). The predefined end-points were vascular death and acute myocardial infarction (AMI). The incidence of end-points was assessed according to the intention-to-treat principle. The post-hoc estimated statistical power was 80%. The rate of death or AMI in the 6-month follow-up period was reduced from 14.9 to 6.8% (-54.4%) (odds ratio: 0.42; confidence intervals: 0.22, 0.80). The incidence of fatal or nonfatal AMI was reduced from 12.2 to 4.3% (-65%) (odds ratio: 0.32; confidence intervals: 0.14, 0.70) and of nonfatal AMI from 10.2 to 3.8% (-63%) (odds ratio: 0.35; confidence intervals: 0.15, 0.80). Nineteen patients died; 12 in the control group (4.7%) and seven in the ticlopidine group (83%) (-36%) (odds ratio: 0.62; confidence intervals: 0.21, 1.74); five patients in the control group and only one in the ticlopidine group died of an AMI. The post-hoc estimated statistical power was 80%. However, we cannot draw definitive conclusions about the clinical effect of ticlopidine treatment in the patients with angina at rest accompanied by transient ischaemic electrocardiographic changes because the subgroup analysis was not planned a priori. Nevertheless, this report strongly suggests that such patients can benefit from antiplatelet treatment with ticlopidine; the benefit mainly depends on the protective effect against myocardial infarction.

Aged↗
PubMed1995

Reduction of requirement for leg vascular surgery during long-term treatment of claudicant patients with ticlopidine: results from the Swedish Ticlopidine Multicentre Study (STIMS).

OBJECTIVE: To study the effect of long-term treatment of the platelet inhibitor ticlopidine as secondary prevention against the need of vascular surgery in patients with intermittent claudication. DESIGN: The Swedish Ticlopidine Multicentre Study (STIMS), was conducted in six medical and surgical clinics of university hospitals in Sweden. METHODS: 687 claudicants were randomised to ticlopidine 250 mg bd or placebo and vascular surgery events were recorded prospectively over a 7-year period. Cox proportional hazards models of risk for leg vascular surgery were constructed using drug treatment and 11 putative risk factors for vascular disease as covariates. Surgical event-free survivals were compared by Kaplan-Meier analysis. RESULTS: The overall rate of first operations was 2.4% per annum. More than half of these operations were in the aortoiliac region. One-quarter of patients operated during the period required further operations but amputation was rare. Ticlopidine treatment reduced the need for vascular reconstructive surgery by about half, both in intention-to-treat and on-treatment analyses (unadjusted relative risks 0.486, 95% CI 0.317-0.745; p < 0.001; 0.493, 95% CI 0.290-0.841: p < 0.01, respectively). In Cox model analysis only male sex was confirmed as a risk factor for surgery. Previous peripheral arterial surgery was the strongest predictor of the need for surgery. None of the risk factors examined interacted statistically with the effect of treatment with ticlopidine. CONCLUSION: In patients with intermittent claudication it seems possible to prevent the need for future vascular surgery by the use of platelet inhibition with ticlopidine.

Female↗
PubMed1996

The STIMS trial: the ticlopidine experience and its clinical applications. Swedish Ticlopidine Multicenter Study.

The mortality in patients with intermittent claudication can be reduced by treatment with ticlopidine. This is the clinically most significant result from STIMS, the Swedish Ticlopidine Multicenter Study. During an average treatment period of 5.6 years, 153 of the 687 patients died, 26.1% in the placebo group and 18.5% in the ticlopidine group (RR0.7, p = 0.015). The incidence of fatal vascular events in the two groups was 12% and 6%. In terms of lives saved per years of treatment, STIMS showed that by treating 200 claudicants for 5 years one can save 13 from a cardiovascular death, not merely dying from something else as treatment was associated with a reduced total mortality as well. The interpretation of the on-treatment analysis is that for those who tolerate the drug the combined vascular morbidity and mortality rate is lowered from 24% to 14%. The disadvantage is that many patients do not tolerate ticlopidine. In STIMS, 22% (2.5 times as many as in the control group) had to stop medication because of gastrointestinal side-effects. Although ticlopidine is associated with an increased risk of leukopenia, the risk in absolute numbers is small: according to STIMS, 4% during 5.6 years. All events were reversible. The 1.4% incidence of thrombocytopenia did not seem to be associated with ticlopidine treatment.

Cerebrovascular Disorders↗
PubMed1998

A double-blind randomized comparison of combined aspirin and ticlopidine therapy versus aspirin or ticlopidine alone on experimental arterial thrombogenesis in humans.

No randomized study comparing the effect of combined ticlopidine and aspirin therapy versus each drug alone in reducing poststenting thrombotic complications has been performed. To compare these three antiplatelet regimens versus placebo, we conducted a double-blind randomized study using an ex vivo model of thrombosis. Sixteen healthy male volunteers were assigned to receive for 8 days the following four regimens separated by a 1-month period: aspirin 325 mg/d, ticlopidine 500 mg/d, aspirin 325 mg/d + ticlopidine 500 mg/d, and placebo. At the end of each treatment period, native nonanticoagulated blood was drawn directly from an antecubital vein over collagen- or tissue factor (TF)-coated coverslips positioned in a parallel-plate perfusion chamber at an arterial wall shear rate (2, 600 s-1 ) for 3 minutes. Thrombus, which formed on collagen in volunteers treated by placebo, were rich in platelets and poor in fibrin. As compared with placebo, aspirin and ticlopidine alone reduced platelet thrombus formation by only 29% and 15%, respectively (P > .2). In contrast, platelet thrombus formation was blocked by more than 90% in volunteers treated by aspirin + ticlopidine (P < .01 v placebo or each treatment alone). Furthermore, the effect of the drug combination therapy was significantly larger than the sum of the two active treatments (P < .05). Thrombus, which formed on TF-coated coverslips in volunteers treated by placebo, were rich in fibrin and platelets. Neither of the three antiplatelet treatments significantly inhibited fibrin deposition and platelet thrombus formation on this surface (P > .2). Thus, the present study shows that combined aspirin and ticlopidine therapy dramatically potentiates the antithrombotic effect of each drug alone, but that the antithrombotic effect of the combined treatment depends on the nature of the thrombogenic surface.

Adult↗
PubMed1997

Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs. Etude de la Ticlopidine après Pontage Fémoro-Poplité and the Association Universitaire de Recherche en Chirurgie.

BACKGROUND: Optimal therapy to prevent late occlusion of arterial bypass grafts in the legs has not been determined. We assessed the effect of ticlopidine, an inhibitor of platelet aggregation, on the long-term patency of saphenous-vein bypass grafts for the treatment of peripheral vascular disease. METHODS: A total of 243 patients with femoropopliteal or femorotibial saphenous-vein bypass grafts were randomly assigned to receive either ticlopidine (250 mg twice a day) or matching placebo for two years. The primary end point was graft patency at two years, as assessed by physical examination, measurement of the ankle brachial index, and duplex ultrasonography or arteriography. The incidence of death and major ischemic events was also analyzed in the two groups. RESULTS: After two years, 66.4 percent of the patients were alive with a patent graft in the ticlopidine group, as compared with 51.2 percent in the placebo group (95 percent confidence interval for the difference between the two groups, 2.9 to 27.4 percent; P=0.02). The two-year cumulative patency rate was 82 percent in the ticlopidine group and 63 percent in the placebo group (P=0.002). There was no significant difference between groups in overall mortality or major ischemic events. CONCLUSIONS: Ticlopidine significantly improved the long-term patency of saphenous-vein bypass grafts in the legs. Since the drug was well tolerated, its use can be recommended after peripheral-vein bypass surgery.

Adult↗
PubMed1992

Clinical study of ticlopidine in diabetic retinopathy. Belgian Ticlopidine Retinopathy Study Group (BTRS).

In this multicentre double-blind study, 100 insulin-treated diabetics with background retinopathy were randomly assigned to treatment with either 250 mg ticlopidine b.i.d. (49 patients) or placebo (51 patients). The primary aim of the study was to assess the evolution of retinopathy by fluorescein angiography performed annually for at least 3 years. The metabolic control of diabetes was evaluated by quarterly assessment of the haemoglobin A1 level. Safety parameters, especially haematologic variables were closely monitored. The proportion of patients with favourable results was higher in the ticlopidine group (55.2%) than in the placebo group (36.6%). However, this difference did not reach statistical significance (p = 0.123), most probably because of the too limited number of patients studied. In the placebo group, a significant relationship was found between the unfavourable evolution of diabetic retinopathy and more fluctuating haemoglobin A1 levels. Such a relationship was not observed in the ticlopidine group. This could be regarded as an expression of the therapeutic effect of the compound. The number and nature of side-effects was similar in both treatment groups. However, the proportion of patients who prematurely discontinued study treatment because of side-effects was significantly higher in the ticlopidine group. Mean levels of biological, and in particular haematologic, parameters did not change significantly except for a significant increase in the cholesterol level in the ticlopidine group, which, however, remained within normal limits.

Adolescent↗