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Y Okutani - One of the best experts on this subject based on the ideXlab platform.
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Ticlopidine induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in japanese patients a preliminary case control study
Pharmacogenomics Journal, 2008Co-Authors: K Hirata, H Takagi, M Yamamoto, T Matsumoto, T Nishiya, K Mori, S Shimizu, H Masumoto, Y OkutaniAbstract:Genetic risk factors for Ticlopidine-induced hepatotoxicity were determined in 22 Japanese patients with Ticlopidine-induced hepatotoxicity and 85 Japanese patients who tolerated Ticlopidine therapy without experiencing adverse reactions. There was a significant correlation between Ticlopidine-induced hepatotoxicity and five human leukocyte antigen (HLA) alleles: HLA-A*3303, HLA-B*4403, HLA-Cw*1403, HLA-DRB1*1302 and HLA-DQB1*0604 (corrected probability (P)-value (Pc)<0.01). In particular HLA-A*3303 was present in 15 (68%) of the 22 patients with Ticlopidine-induced hepatotoxicity and in 12 (14%) of the 85 Ticlopidine-tolerant patients (odds ratio, 13.04; 95% confidence interval (CI), 4.40–38.59; the corrected P-value (Pc)=1.24 × 10–5). HLA-A*3303 was present in 12 (86%) of the 14 patients with Ticlopidine-induced cholestatic hepatotoxicity (odds ratio, 36.50; 95% CI, 7.25–183.82, Pc=7.32 × 10–7). Ticlopidine-induced severe cholestatic hepatotoxicity occurred more frequently in subjects with HLA-A*3303 and its haplotype in Japanese patients. These findings may explain the high incidence of Ticlopidine-induced hepatotoxicity in Japanese patients mediated via an immune-mediated mechanism.
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Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case–control study
The Pharmacogenomics Journal, 2008Co-Authors: K Hirata, H Takagi, M Yamamoto, T Matsumoto, T Nishiya, K Mori, S Shimizu, H Masumoto, Y OkutaniAbstract:Genetic risk factors for Ticlopidine-induced hepatotoxicity were determined in 22 Japanese patients with Ticlopidine-induced hepatotoxicity and 85 Japanese patients who tolerated Ticlopidine therapy without experiencing adverse reactions. There was a significant correlation between Ticlopidine-induced hepatotoxicity and five human leukocyte antigen (HLA) alleles: HLA-A^*3303, HLA-B^*4403, HLA-Cw^*1403, HLA-DRB1^*1302 and HLA-DQB1^*0604 (corrected probability ( P )-value ( Pc )
Peter B Berger - One of the best experts on this subject based on the ideXlab platform.
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meta analysis of randomized and registry comparisons of Ticlopidine with clopidogrel after stenting
Journal of the American College of Cardiology, 2002Co-Authors: Deepak L Bhatt, Peter B Berger, Michel E Bertrand, Philippe L Lallier, Issam Moussa, Jeffrey W Moses, George Dangas, Megumi Taniuchi, John M Lasala, David R HolmesAbstract:Abstract Objectives We sought to determine whether clopidogrel is at least as efficacious as Ticlopidine. Background Several trials have supported the enhanced safety and tolerability of clopidogrel compared with Ticlopidine after coronary stent deployment. However, none of these individual trials were powered to detect possible differences in the efficacy for reducing ischemic end points. Methods Published data from trials and registries that compared clopidogrel with Ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed. The rate of 30-day major adverse cardiac events (MACE), as defined in each trial, was used as the primary end point. Results There were a total of 13,955 patients. The pooled rate of major adverse cardiac events was 2.10% in the clopidogrel group and 4.04% in the Ticlopidine group. After adjustment for heterogeneity in the trials, the odds ratio (OR) of having an ischemic event with clopidogrel, as compared with Ticlopidine, was 0.72 (95% confidence interval [CI] 0.59 to 0.89, p = 0.002). Mortality was also lower in the clopidogrel group compared with the Ticlopidine group—0.48% versus 1.09% (OR 0.55, 95% CI 0.37 to 0.82; p = 0.003). Conclusions Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as Ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace Ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment.
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Does Ticlopidine reduce reocclusion and other adverse events after successful balloon angioplasty of occluded coronary arteries? Results from the Total Occlusion Study of Canada (TOSCA)
American Heart Journal, 2001Co-Authors: Peter B Berger, Diane Catellier, Vladimir Džavik, Ian M. Penn, Christopher E. BullerAbstract:Objectives: Ticlopidine reduces stent thrombosis and other adverse events among patients receiving coronary stents. Whether Ticlopidine is beneficial after balloon angioplasty is unknown. Our purpose was to compare the clinical outcome of patients undergoing balloon angioplasty treated with both aspirin and Ticlopidine versus aspirin alone. Methods and Results: We performed a databank analysis of the Total Occlusion Study of Canada (TOSCA), a randomized trial with angiographic follow-up comparing the frequency of reocclusion after angioplasty of a subtotal or total coronary occlusion in patients receiving ≥1 heparin-coated Palmaz-Schatz stent versus balloon angioplasty alone. In TOSCA, 102 patients undergoing balloon angioplasty were treated with both aspirin and Ticlopidine (generally for 15-30 days) and 94 were treated with aspirin alone, by physician preference. After 6 months, failure to sustain patency (less than Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow on follow-up angiography) occurred in 23% of patients on Ticlopidine and aspirin versus 16% of patients on aspirin alone (P = .21); the frequency of target vessel revascularization was also similar in the 2 groups (32% vs 25%, P = .27). Myocardial infarction was infrequent in both groups (2.0% vs 1.1%, respectively, P not significant). Patients treated with aspirin and Ticlopidine had more adverse angiographic and procedural characteristics, including longer lesions and treatment lengths. Multivariate analysis to adjust for these and other differences failed to reveal a benefit of Ticlopidine in maintaining patency and reducing adverse clinical events. Conclusions: After balloon angioplasty of a subtotal or total coronary occlusion, no reduction in adverse events was observed among patients in whom Ticlopidine was added to aspirin, even after adjustment for clinical and lesion characteristics.
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results of the ticlid or plavix post stents topps trial do they justify the switch from Ticlopidine to clopidogrel after coronary stent placement
Trials, 2000Co-Authors: Peter B BergerAbstract:In the Ticlid or Plavix Post-Stents (TOPPS) trial, 1016 patients undergoing successful coronary stent placement were randomized to receive aspirin and either Ticlopidine or clopidogrel. In this trial, the dosages and regimens of Ticlopidine and clopidogrel resembled more closely those used in most catheterization laboratories than did the two previous randomized trials comparing Ticlopidine and clopidogrel. The results of the TOPPS trial support the current practice of substituting Ticlopidine for clopidogrel in stent patients.
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clopidogrel versus Ticlopidine after intracoronary stent placement
Journal of the American College of Cardiology, 1999Co-Authors: Peter B Berger, Charanjit S Rihal, Malcolm R Bell, Henry Ting, Gregory W Barsness, Kirk N Garratt, Victoria Bellot, Verghese Mathew, Steve Melby, Lavon HammesAbstract:Abstract OBJECTIVES The study compared the safety and efficacy of Ticlopidine with clopidogrel in patients receiving coronary stents. BACKGROUND Stent thrombosis is reduced when Ticlopidine is administered with aspirin. Clopidogrel is similar to Ticlopidine in chemical structure and function but has fewer side effects; few data are available about its use in stent patients. METHODS We compared 30-day event rates in 500 consecutive coronary stent patients treated with aspirin and clopidogrel (300 mg loading dose immediately prior to stent placement, and 75 mg/day for 14 days) to 827 consecutive stent patients treated with aspirin and Ticlopidine (500 mg loading dose and 250 mg twice daily for 14 days). RESULTS Patients treated with clopidogrel had more adverse clinical characteristics including older age, more severe angina, and more frequent infarction within the prior 24 h. Nonetheless, mortality was 0.4% in clopidogrel patients versus 1.1% in Ticlopidine patients; nonfatal myocardial infarction occurred in 0% versus 0.5%, stent thrombosis in 0.2% versus 0.7%, bypass surgery or repeat angioplasty in 0.4% versus 0.5%, and any event occurred in 0.8% versus 1.6% of patients, respectively (p = NS). Based on the observed 30-day event rate of 1.6% with Ticlopidine, the statistical power of the study was 43% to detect an even rate of 0.5% with clopidogrel, and 75% to detect an event rate with of 4% with clopidogrel, with a p value of 0.05. CONCLUSIONS These data indicate that clopidogrel can be safely substituted for Ticlopidine in patients receiving coronary stents.
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timing of coronary stent thrombosis in patients treated with Ticlopidine and aspirin
American Journal of Cardiology, 1999Co-Authors: Stephanie H Wilson, Charanjit S Rihal, Malcolm R Bell, James L Velianou, David R Holmes, Peter B BergerAbstract:In patients receiving coronary stents treated with aspirin and coumadin, the peak incidence of stent thrombosis occurs on the fifth and sixth days following the implantation procedure. Little is known about the timing of stent thrombosis in patients treated with aspirin and Ticlopidine. We compared the timing of coronary stent thrombosis in patients treated with Ticlopidine and aspirin with the timing in those receiving coumadin and aspirin. A retrospective databank analysis was performed and 39 patients were identified who experienced stent thrombosis after successful coronary stent implantation. Of these, 21 had been treated with Ticlopidine and aspirin and 18 with coumadin and aspirin therapy. The median time from stent implantation to stent thrombosis in the Ticlopidine and aspirin group was 12 hours (interquartile range 6 to 72 hours) compared with 4 days in the coumadin and aspirin group (interquartile range 21 to 68 hours) (p <0.0001). There was no significant difference between the timing of stent thrombosis in patients treated with abciximab in addition to Ticlopidine and aspirin (median 17 hours, interquartile range 6 to 29) versus Ticlopidine and aspirin patients who did not receive abciximab (median 11 hours, interquartile range 9 to 12, p = 0.57). Thus, in patients who receive coronary stents, stent thrombosis occurs much earlier after the procedure in patients treated with Ticlopidine and aspirin than in patients treated with anticoagulation therapy.
K Hirata - One of the best experts on this subject based on the ideXlab platform.
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Ticlopidine induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in japanese patients a preliminary case control study
Pharmacogenomics Journal, 2008Co-Authors: K Hirata, H Takagi, M Yamamoto, T Matsumoto, T Nishiya, K Mori, S Shimizu, H Masumoto, Y OkutaniAbstract:Genetic risk factors for Ticlopidine-induced hepatotoxicity were determined in 22 Japanese patients with Ticlopidine-induced hepatotoxicity and 85 Japanese patients who tolerated Ticlopidine therapy without experiencing adverse reactions. There was a significant correlation between Ticlopidine-induced hepatotoxicity and five human leukocyte antigen (HLA) alleles: HLA-A*3303, HLA-B*4403, HLA-Cw*1403, HLA-DRB1*1302 and HLA-DQB1*0604 (corrected probability (P)-value (Pc)<0.01). In particular HLA-A*3303 was present in 15 (68%) of the 22 patients with Ticlopidine-induced hepatotoxicity and in 12 (14%) of the 85 Ticlopidine-tolerant patients (odds ratio, 13.04; 95% confidence interval (CI), 4.40–38.59; the corrected P-value (Pc)=1.24 × 10–5). HLA-A*3303 was present in 12 (86%) of the 14 patients with Ticlopidine-induced cholestatic hepatotoxicity (odds ratio, 36.50; 95% CI, 7.25–183.82, Pc=7.32 × 10–7). Ticlopidine-induced severe cholestatic hepatotoxicity occurred more frequently in subjects with HLA-A*3303 and its haplotype in Japanese patients. These findings may explain the high incidence of Ticlopidine-induced hepatotoxicity in Japanese patients mediated via an immune-mediated mechanism.
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Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case–control study
The Pharmacogenomics Journal, 2008Co-Authors: K Hirata, H Takagi, M Yamamoto, T Matsumoto, T Nishiya, K Mori, S Shimizu, H Masumoto, Y OkutaniAbstract:Genetic risk factors for Ticlopidine-induced hepatotoxicity were determined in 22 Japanese patients with Ticlopidine-induced hepatotoxicity and 85 Japanese patients who tolerated Ticlopidine therapy without experiencing adverse reactions. There was a significant correlation between Ticlopidine-induced hepatotoxicity and five human leukocyte antigen (HLA) alleles: HLA-A^*3303, HLA-B^*4403, HLA-Cw^*1403, HLA-DRB1^*1302 and HLA-DQB1^*0604 (corrected probability ( P )-value ( Pc )
Ian Chinyee - One of the best experts on this subject based on the ideXlab platform.
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thrombotic thrombocytopenic purpura associated with Ticlopidine
Annals of Pharmacotherapy, 1993Co-Authors: Michael J Kovacs, Patrick Y Soong, Ian ChinyeeAbstract:OBJECTIVE:To report a case of possible Ticlopidine-induced thrombotic thrombocytopenic purpura (TTP).CASE SUMMARY:A 68-year-old man was started on Ticlopidine therapy for transient ischemic attack because of aspirin intolerance. Three weeks after starting therapy, the patient developed TTP, manifest by severe thrombocytopenia, renal failure, microangiopathic hemolytic anemia, and neurologic symptoms. The condition reversed over three to five days coincident with the discontinuation of Ticlopidine and therapy with daily plasma infusion and exchange. No evidence of relapse was found at one-year follow-up.DISCUSSION:TTP is a well-defined clinical entity with varied etiologies. Ticlopidine has been reported as causing neutropenia and isolated thrombocytopenia. Case reports have linked Ticlopidine to the development of TTP.CONCLUSIONS:Including this case there are now seven patients who have been documented as developing TTP while receiving Ticlopidine. In addition to monitoring for neutropenia and isolated th...
R Terrena - One of the best experts on this subject based on the ideXlab platform.
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thrombotic thrombocytopenic purpura related to Ticlopidine
The Lancet, 1991Co-Authors: Y Page, Fabrice Zeni, B Tardy, C Comtet, J C Bertrand, R TerrenaAbstract:Abstract 4 patients had typical features of thrombotic thrombocytopenic purpura (TTP) after 3 to 8 weeks of Ticlopidine therapy. In 2 Ticlopidine was the only medication taken before TTP; in another, rechallenge with drugs other than Ticlopidine that the patient had been taking did not produce relapse. In all patients the delay between start of Ticlopidine and TTP was in the same range as the latent period before Ticlopidine-induced neutropenia. No relapse occurred in the 4 to 43 months of follow-up in the 3 surviving patients.