thienopyridine and Myocardial-Ischemia

Adenosine diphosphate (ADP)-induced platelet activation plays a pivotal role in the thrombocyte aggregation and pathogenesis of ischemic heart disease. The long-term benefit of dual anti-platelet therapy with ADP-receptor antagonists, such as clopidogrel, in combination with aspirin is well established for patients following coronary stent implantation. This review discusses latest developments in the field of ADP-receptor antagonists.

Topics: Acute Coronary Syndrome; Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Aspirin; Clopidogrel; Combined Modality Therapy; Humans; Myocardial Ischemia; Platelet Aggregation Inhibitors; Pyridines; Receptors, Purinergic P2; Stents; Ticlopidine

Prasugrel was associated with a statistically significant reduction in rates of cardiac ischemic events in patients with ACS who had undergone PCI. Rates of post-PCI death from cardiovascular causes, nonfatal MI, or nonfatal stroke were also significantly reduced with the use of prasugrel versus clopidogrel. Major bleeding was significantly increased with the use of prasugrel versus clopidogrel. Mortality did not differ significantly between the groups.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Confidence Intervals; Double-Blind Method; Drug Therapy, Combination; Humans; Myocardial Ischemia; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Thiophenes; Ticlopidine

Previous observational studies have evaluated the utility of prolonged thienopyridine therapy in patients receiving drug-eluting stents, with conflicting results. A landmark analysis was therefore performed on the basis of the prospective, double-blind TAXUS-II SR, TAXUS-IV, and TAXUS-V trials. Of 2,736 randomized patients, 2,171 were event free at 1 year, of whom 964 (44.4%) at physician discretion were still taking thienopyridines at that time. Among the 1,141 event-free patients randomized to Taxus stents, a trend was present in those patients still taking compared with those having discontinued thienopyridines at 1 year to have numerically fewer very late stent thrombosis episodes at 2 years (0 vs 4 [0.7%] events, respectively, p = 0.07) and 5 years (4 [0.8%] vs 8 [1.4%] events, respectively, p = 0.43). However, in event-free Taxus patients taking compared with those not taking thienopyridines at 1 year, there were no significant differences in the 2- and 5-year rates of death (1.4% vs 0.6%, p = 0.22, and 6.0% vs 7.4%, p = 0.83, respectively) and death or myocardial infarction (1.8% vs 1.9%, p = 0.82, and 8.3% vs 9.8%, p = 0.75, respectively). There were no significant interactions between 1-year thienopyridine use status and stent type (Taxus vs bare-metal stent) on the individual or composite end points of stent thrombosis, death, or myocardial infarction at either 2 or 5 years (all interaction p values >0.50). In conclusion, thienopyridine use beyond 1 year after drug-eluting stent implantation may reduce stent thrombosis over the subsequent 12-month period, but the rates of death and myocardial infarction at 2 and 5 years are not prevented by extended thienopyridine use after either drug-eluting or bare-metal stent implantation.

Topics: Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Coronary Angiography; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Pyridines; Secondary Prevention; Stents; Time Factors; Treatment Outcome

Few studies have examined whether high-responsiveness to antiplatelet therapy is associated with an increased risk of bleeding in patients receiving dual antiplatelet therapy.. Elective drug-eluting stent implantation was performed in 184 patients treated with aspirin and a thienopyridine (200 mg/day of ticlopidine or 75 mg/day of clopidogrel). The subjects were divided into 3 groups according to post-treatment platelet reactivity before stenting as measured by the response to adenosine diphosphate: the 1(st) quartile group was defined as high-responders, the 4(th) as low-responders, and the other 2 quartiles as middle-responders. Major bleeding occurred more frequently in high-responders than in middle- or low-responders during an average of 16 months' follow-up (15 vs 4, 2%, P=0.02). High-responsiveness was the independent predictor of major bleeding (odds ratio 4.26, P=0.03). Adverse cardiac events were less frequent in high- and middle-responders than in low-responders (24, 16 vs 37%, P=0.02). Middle-responders had better net clinical outcomes, defined as the sum of major bleeding and adverse cardiac events, than did high- or low-responders (21 vs 39, 39%, P=0.02).. In the present study high-responsiveness to antiplatelet therapy was associated with an increased risk of bleeding with no reduction in adverse cardiac events. Measuring platelet reactivity may be useful for risk stratification according to bleeding complications, as well as adverse cardiac events, in patients treated with drug-eluting stents.

Topics: Aged; Angioplasty, Balloon, Laser-Assisted; Aspirin; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Pyridines; Retrospective Studies; Risk Factors; Ticlopidine; Treatment Outcome