thienopyridine and Cardiovascular-Diseases

Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is an established regimen to reduce the risk of ischemic event occurrence in patients with high-risk cardiovascular (CV) disease. Cigarette smoking is an important cardiovascular risk factor. However, several investigators have reported what may be termed a "new" "smoker's paradox", whereby clopidogrel-treated nonsmokers appear to have either less or no CV-event reduction when compared to the substantial CV-event reduction in clopidogrel-treated smokers based on several large-scale trials. This "smoker's paradox" observed in multiple clinical outcome studies is also supported by emerging "real-world" data that also suggest clopidogrel nonsmokers do not fare as well as smokers treated with clopidogrel. In support of the new "smoker's paradox", pharmacodynamic studies have also shown that smoking status influences clopidogrel responsiveness in healthy volunteers, acute coronary syndrome patients, and patients treated with percutaneous coronary intervention. Finally, there is a substantial, albeit not entirely consistent, body of pharmacodynamic and clinical outcome data supporting a reduced antiplatelet effect of clopidogrel in non-smokers as compared to smokers. The clinical relevance of this interaction has never been demonstrated in a prospective trial. The focus of this review is to critically evaluate the reported interaction between cigarette smoking status and thienopyridine efficacy.

Topics: Cardiovascular Diseases; Humans; Pyridines; Risk Factors; Smoking; Treatment Outcome

Topics: Adenosine; Cardiovascular Diseases; Clopidogrel; Coronary Artery Disease; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Antiplatelet therapy is used to reduce the risk of ischemic events in patients with cardiovascular disease. The balance of benefits and risks of antiplatelet drugs in cardiovascular disease has been evaluated in large-scale randomised trials, however the absolute benefit for an individual patient and a specific platelet-active drug needs further evaluation. Several well-conducted studies have demonstrated a substantial inter-individual variability in platelet responsiveness to drugs. The historical "gold standard" test of platelet function (optical aggregation) has been extensively used for measuring the effect of antiplatelet drugs, but has limitations. New tests developed (i.e. PFA-100®, VerifyNow®) may overcome some of these limitations but they do not correlate well with each other. Despite these unresolved methodological questions, several recent clinical studies, but not all, suggest a significant correlation between antiplatelet resistance status and serious vascular events. In these conditions, laboratory monitoring for antiplatelet therapies raises several questions: (i) the necessity of a consensus regarding the definition of resistance and the relevant test, (ii) the demonstration that biological resistance has clinical significance, and (iii) the clinical impact of individually adjusting the antiplatelet therapy. Therefore, it is not currently appropriate to test patients or to change therapy on the basis of such tests, other than in prospective and adequately powered clinical trials.

Topics: Aspirin; Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors; Pyridines

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the fifth communication we consider data of two randomized studies in which efficacy and safety of clopidogrel in combination with acetylsalicylic acid (ASA) has been assessed in comparison with ASA in stable patients with atherothrombotic cardiovascular disease. It has been shown in both studies that in stable patients with atherothrombotic cardiovascular disease long-term therapy with combination of clopidogrel and ASA was no more effective than monotherapy with ASA or clopidogrel but was associated with high risk of hemorrhagic complications. Thus contrary to acute coronary syndromes and percutaneous interventions with stenting combinations of clopidogrel and ASA is not indicated to patients with stable course cardiovascular diseases.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Arteriosclerosis; Aspirin; Cardiovascular Diseases; Clopidogrel; Coronary Circulation; Death, Sudden, Cardiac; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Streptokinase; Stroke; Thrombosis; Ticlopidine; Time Factors

The prevalence of Type 2 diabetes mellitus (DM) continues to increase globally and brings with it a parallel increase in the associated cardiovascular disease complications. Despite advances in evidence-based therapies for cardiovascular disease risk modification, many of which are especially effective among patients with DM, there remains a residual degree of cardiovascular disease risk associated with DM, yielding opportunity for continued clinical advances. Given the myriad perturbations of platelet function associated with DM, improvements in antiplatelet therapies hold particular promise for this high-risk population of patients, with emerging data from ex vivo assessments and clinical outcomes trials providing a basis of support for this concept.

Topics: Aspirin; Blood Platelets; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Risk

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the first communication pharmacodynamics and pharmacokinetics of the first thienopyridine ticlopidine are described in detail. Results of randomized studies in which cerebro and cardioprotective efficacy and safety of ticlopidine was studied in patients with cerebrovascular, peripheral artery diseases, and acute coronary syndromes are discussed. It has been established that ticlopidine is more effective and safe in patients having undergone coronary and femoral bypass surgery. Results of meta analyses have shown which evidence that ticlopidine is not less and may be more effective than clopidogrel in patients after coronary bypass surgery. Most frequent and most severe side effects of ticlopidine and measures of their prevention are also considered.

Topics: Cardiovascular Diseases; Humans; Platelet Aggregation Inhibitors; Pyridines; Ticlopidine; Treatment Outcome

One of the major classes of adenosine diphosphate (ADP) receptor antagonists are thienopyridines. Thienopyridines compose a subcategory of antiplatelet medications, known as ADP receptor inhibitors, used commonly for the treatment of atherosclerotic cardiovascular disease. Thienopyridines, including ticlopidine, clopidogrel and prasugrel, are prodrugs administered orally that are further metabolized by hepatocytes to create active metabolites that irreversibly bind ADP receptors located on the platelet membrane. Thus, these selected drugs have an inhibitory effect for the duration of the platelet's lifespan of 7-10 days. The goal of this manuscript is to review the currently available ADP receptor blockers with emphasis on chemical structure, mode of action and clinical use.

Topics: Cardiovascular Diseases; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Thrombosis

Proton-pump inhibitors (PPIs) are often prescribed in combination with thienopyridines. Conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use, measures of platelet function, and clinical outcomes for patients treated with clopidogrel or prasugrel.. In the PRINCIPLE-TIMI 44 trial, the primary outcome was inhibition of platelet aggregation at 6 h assessed by light-transmission aggregometry. In the TRITON-TIMI 38 trial, the primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke. In both studies, PPI use was at physician's discretion. We used a multivariable Cox model with propensity score to assess the association of PPI use with clinical outcomes.. In the PRINCIPLE-TIMI 44 trial, 201 patients undergoing elective percutaneous coronary intervention were randomly assigned to prasugrel (n=102) or high-dose clopidogrel (n=99). Mean inhibition of platelet aggregation was significantly lower for patients on a PPI than for those not on a PPI at 6 h after a 600 mg clopidogrel loading dose (23.2+/-19.5% vs 35.2+/-20.9%, p=0.02), whereas a more modest difference was seen with and without a PPI after a 60 mg loading dose of prasugrel (69.6+/-13.5% vs 76.7+/-12.4%, p=0.054). In the TRITON-TIMI 38 trial, 13,608 patients with an acute coronary syndrome were randomly assigned to prasugrel (n=6813) or clopidogrel (n=6795). In this study, 33% (n=4529) of patients were on a PPI at randomisation. No association existed between PPI use and risk of the primary endpoint for patients treated with clopidogrel (adjusted hazard ratio [HR] 0.94, 95% CI 0.80-1.11) or prasugrel (1.00, 0.84-1.20).. The current findings do not support the need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel or prasugrel.. Daiichi Sankyo Company Limited and Eli Lilly and Company sponsored the trials. This analysis had no funding.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Diseases; Clopidogrel; Drug Interactions; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Proton Pump Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Risk Factors; Thiophenes; Ticlopidine; Treatment Outcome

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the second communication we describe in detail clinical pharmacokinetics and pharmacodynamics of the most often used thienopyridine derivative - clopidogrel. We discuss results of randomized studies and clinical observations which have shown that pharmacokinetics of clopidogrel might vary substantially in dependence of polymorphisms of genes responsible for synthesis of P2Y12 receptors of platelets or cytochromic isoenzymes P-450 CYP of liver with participation of which formation of active metabolite of clopidogrel occurs. Contrary to practically healthy people in patients with various forms of ischemic heart disease (IHD) concomitant therapy, for instance some statins and calcium antagonists, can affect clopidogrel pharmacokinetics. Pharmacodynamics of clopidogrel in patients with IHD with acute coronary syndrome or diabetes mellitus or before percutaneous coronary interventions (PCI) also differs from that in healthy people, because in these patients hyperaggregation of platelets takes place initially and antiaggregatory action of clopidogrel is less expressed. In 10-30% of patients with IHD partial or complete resistance to antiaggregation action of clopidogrel is detected, which according to some observations is combined with elevated risk of thrombotic cardiac complications after PCI. Possible causes of resistance to clopidogrel and ways of its overcoming are discussed.

Topics: Cardiovascular Diseases; Clopidogrel; Humans; Platelet Aggregation Inhibitors; Pyridines; Ticlopidine; Treatment Outcome

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the third communication we consider data of randomized studies in which efficacy and safety of clopidogrel monotherapy has been assessed in comparison with acetylsalicylic acid (ASA), ticlopidine, warfarin, as well as ASA in combination with extended release form of dipyridamole in various cardio-vascular diseases. Results of these studies indicate that efficacy of monotherapy with clopidogrel is comparable with that of ASA, ticlopidine, warfarin, and ASA in combination with extended release form of dipyridamole. Clopidogrel significantly more rarely causes ulcerogenic and other hemorrhagic complications than ticlopidine, but is substantially more expensive. Therefore prescribing of clopidogrel as monotherapy is justified only in those cases when ASA and ticlopidine are contraindicated or induce pronounced side effects.

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Ticlopidine; Ulcer

Agents with antiplatelet and anticoagulant activity have been proved to be effective in reducing the incidence of complications following acute coronary syndrome, percutaneous coronary intervention, and cardiopulmonary bypass. However, these agents, including heparin, glycoprotein IIb/IIIa receptor inhibitors, and thienopyridines, are associated with increased risk of bleeding and thrombocytopenia and have been administered together with increasing frequency in a variety of cardiovascular settings. Therefore, clinicians must be familiar with the safety and rational use of these potent antithrombotic agents. Clinical features of thrombocytopenia range from bleeding to thrombosis, even death, and therapy is very different depending on the underlying cause. Additionally, patients may sometimes need urgent intervention or surgery. Thus, it is essential to quickly discriminate the etiology and start appropriate therapy. This review highlights the pathogenesis, clinical and laboratory manifestation, differential diagnosis, and treatment of antithrombotic drug-induced thrombocytopenia in cardiovascular diseases.

Topics: Cardiovascular Diseases; Diagnosis, Differential; Drug Monitoring; Fibrinolytic Agents; Heparin; Humans; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Thrombocytopenia

Platelets from patients affected by diabetes mellitus and metabolic syndrome show an impaired sensitivity to physiological antiaggregating agents and an enhanced activation state, mirrored by an increased expression of membrane activation markers; furthermore, they are more prone to form spontaneous microaggregates with ADP receptor involvement. These abnormalities are responsible for a pro-thrombotic condition, contributing to a high cardiovascular risk. This pattern of platelet abnormalities provides a strong rationale for aggressive antiplatelet therapy strongly recommended by guidelines both in diabetes mellitus and in metabolic syndrome, not only in the setting of acute coronary syndromes, but also for the long-term prevention of the cardiovascular events. Antiplatelet therapy in these pathological conditions, however, is still a matter of intense debate, especially because a high prevalence of "resistance" to these drugs (and to aspirin in particular) has been described in these patients. This may result in non-significant reductions in cardiovascular events. Different factors seem to be involved, including: i) genetic polymorphisms; ii) hyperglycemia and poor metabolic control; iii) reduced sensitivity to nitric oxide; iv) a pro-inflammatory and/or pro-thrombotic status, and, v) increased oxidative stress. This review will take into consideration: i) the results of the most relevant studies addressing the effects of the anti-aggregating treatment in patients affected by diabetes mellitus and/or metabolic syndrome, and, ii) the biochemical mechanisms accounting for the impaired sensitivity to aspirin and thienopyridines in the above mentioned clinical conditions.

Topics: Aspirin; Cardiovascular Diseases; Diabetes Mellitus; Drug Resistance; Humans; Metabolic Syndrome; Platelet Activation; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyridines; Risk Factors

Platelets play an important role in atherothrombotic disease, as well as in the pathogenesis of atherosclerosis and in complications. Antiplatelet therapy with clopidogrel represents at present an important treatment of coronary artery disease (CAD), especially in and after acute coronary syndromes (ACS), and after coronary interventions when stents are used. Clopidogrel is a potent and specific inhibitor of platelet ADP receptor (P2Y(12) receptor) with high antithrombotic activity. Emerging data suggest that a significant percentage of individuals treated with clopidogrel do not receive the expected therapeutic benefit because of a decreased responsiveness of their platelets, which is caused by several extrinsic and/or intrinsic mechanisms. As long as clopidogrel is the "gold standard" in combination with aspirin in the treatment of patients undergoing percutaneous coronary intervention and stent implantation, the overall challenge is to develop a fast "point-of-care" assay to detect clopidogrel resistance early and to enable alternative antithrombotic strategies in non-responders or low-responders. This test should be easily performed (bedside) and reproducible, with a standardized definition of response, which is known to correlate with clinical outcomes. Unfortunately, such a test does not exist at present. As an alternative, new ADP receptor antagonists with better bioavailability and improved pharmacokinetics, e.g. intestinal reabsorption as an active drug or 1:1 conversion into an active metabolite thus reducing individual variations, are in development and have already found their way into clinical use in phase-3 trials. Prasugrel is one of the incoming new drugs with high expectations, but other agents might follow in the near future.

Topics: Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Design; Drug Resistance; Drugs, Investigational; Humans; Membrane Proteins; Piperazines; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Pyridines; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Thiophenes; Ticlopidine

The importance of the dissolution and prevention of thrombosis in treating patients with ST-segment elevation myocardial infarction (STEMI) has motivated the development of novel therapies targeting platelet aggregation and thrombus formation. In contemporary practice, the current challenge is the integration of these therapies into reperfusion strategies that may include fibrinolytic therapy or percutaneous coronary revascularization (PCI). Evidence from clinical trials shows that addition of glycoprotein IIb/IIIa inhibition to PCI for treatment of STEMI has substantially lowered the incidence of recurrent ischemic events and improved early survival. In contrast, current trials evaluating a strategy termed facilitated PCI, or planned early PCI after pharmacologic reperfusion therapy, have presently demonstrated an increased risk of bleeding events and mortality. Additional trials have extended the role of antithrombotic agents to STEMI that previously were reserved for patients undergoing elective revascularization or among those treated with non-ST-segment elevation acute coronary syndromes. For example, the recent studies have demonstrated the benefit of clopidogrel treatment among STEMI patients treated with fibrinolysis in reducing the incidence of infarct artery reocclusion and improving early survival. Other anticoagulants under investigation in the management of STEMI include enoxaparin, bivalirudin, and fondaparinux. This review summarizes the current status of pharmacologic and invasive strategies for the treatment of STEMI and describes recent and ongoing directions for clinical investigation.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Platelets; Cardiovascular Diseases; Clinical Trials as Topic; Combined Modality Therapy; Drug Therapy, Combination; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Research Design; Treatment Outcome

Platelet activation and aggregation are considered to be central to arterial thrombus formation. Antiplatelet therapy is therefore important for both the treatment and prevention of cardiovascular disease. Aspirin, the most widely used antiplatelet agent, inhibits platelet cyclo-oxygenase and the conversion of arachidonic acid to the potent platelet agonist thromboxane A(2) but does not prevent platelet activation occurring via various signalling pathways that are independent of thromboxane A(2) release. Therefore a number of other compounds have been developed to complement aspirin's beneficial effect. These include the thienopyridines (clopidogrel and ticlopidine), dipyridamole, and the alpha(IIb)beta(3) (glycoprotein IIb/IIIa) receptor inhibitors.

Topics: Aspirin; Cardiovascular Diseases; Dipyridamole; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines

Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown.. To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses.. International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014.. Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES.. Stent thrombosis, MACCE, and moderate or severe bleeding.. Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001).. Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Aged; Aspirin; Cardiovascular Diseases; Coronary Restenosis; Double-Blind Method; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Intention to Treat Analysis; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyridines; Risk; Stents

Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y(12) receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel.. Joint Utilization of Medications to Block Platelets Optimally-Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant (TIMI major plus minor) non-CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically lower incidences of the primary efficacy composite end point (30-day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis.. In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety.

Topics: Adolescent; Adult; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Clopidogrel; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemorrhage; Humans; Incidence; Male; Membrane Proteins; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Pyridines; Receptors, Purinergic P2Y12; Thiophenes; Ticlopidine

Although combination therapy for various cardiac conditions with dual antiplatelet therapy (aspirin and thienopyridine derivatives) and warfarin sodium has become increasingly popular, the safety and effectiveness of this aggressive treatment regimen remain unknown.. We retrospectively enrolled and analyzed 575 consecutive patients who had been implanted with drug-eluting coronary stents. The primary and secondary endpoints were major bleeding complications and major adverse cardiovascular events (MACE), respectively. At the time of discharge, 525 patients (91.3%) were prescribed with dual antiplatelet therapy, and 50 (8.7%) of them received dual antiplatelet plus anticoagulant therapy (triple therapy). The patients treated with triple therapy had a greater prevalence of comorbid conditions, including left ventricular systolic dysfunction and multi-vessel coronary disease compared to those on the dual antiplatelet regimen. During a median follow-up of 459 days, 14 (2.7%) patients receiving dual, and 9 (18.0%) receiving triple therapy reached the primary endpoint (p<0.001). These results show that warfarin use was associated with an increased risk of subsequent major bleeding. On the other hand, the incidence of MACE did not differ between the two groups (p=0.108 by the log-rank test). Multivariate analysis showed that renal impairment was an independent predictor of the risk of subsequent major bleeding in the triple therapy group.. Triple therapy increased the hemorrhagic complications in patients after percutaneous coronary intervention with drug-eluting stents, especially in patients with impaired renal function. Great caution should be taken with patients who necessitate the addition of anticoagulation therapy with warfarin to dual antiplatelet therapy.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Diseases; Coronary Disease; Drug-Eluting Stents; Female; Hemorrhage; Humans; Kidney Diseases; Male; Platelet Aggregation Inhibitors; Prognosis; Pyridines; Retrospective Studies; Ventricular Dysfunction; Warfarin

The efficacy and safety of new antiplatelet therapies, as well as antiplatelet therapies in development, are reviewed.. Variability in the response to treatment with aspirin has been recognized for more than 40 years. Thienopyridine antiplatelet agents are now a standard pharmacologic component in the management of patients undergoing percutaneous coronary intervention (PCI) and stent placement. However, investigators have recently described wide inter-individual variability in the level of platelet inhibition following treatment with the thienopyridine clopidogrel, with a small number of patients classified as "non-responders" or "resistant." Such variability in response is likely to have important clinical implications, because antiplatelet therapy plays a key role in the prevention and treatment of cardiovascular disease, For example, recent studies have demonstrated that diminished response to clopidogrel may be associated with increased cardiac events after PCI. Even with larger-than-approved loading doses, clopidogrel requires several hours to reach a steady-state effect, and therapy must be discontinued for several days prior to surgery in order to avoid major bleeding events. Clinical trials of prasugrel, a new oral thienopyridine with a more rapid onset of platelet inhibition, have demonstrated significant reductions in adverse cardiovascular outcomes and stent thrombosis; however, there is an increased risk for major bleeding events with prasugrel in some subgroups of the study populations. These limitations have led to development of agents that may potentially overcome such clinical challenges. AZD6140, a novel, potent oral P2Y12 antagonist, demonstrated more effective platelet inhibition versus clopidogrel in a large randomized trial of patients with acute coronary syndrome. However, patients taking AZD6140 reported dyspnea significantly more frequently than those taking clopidogrel. Cangrelor, a novel intravenous P2Y(12) receptor antagonist with a rapid onset of action and complete reversibility of platelet inhibition within 20-50 minutes of administration, may offer advantages over currently approved antiplatelet therapies. A new oral antiplatelet thrombin-receptor antagonist, TRA-SCH 530348, is in early clinical trials. Unlike currently available drugs, TRA-SCH 530348 effectively prevents thrombin-induced activation of platelets.. Each new class of antiplatelet therapies has the potential for specific benefits and adverse effects in clinical use.

Topics: Cardiovascular Diseases; Drugs, Investigational; Humans; Platelet Aggregation Inhibitors; Pyridines; Research; Treatment Outcome

Topics: Adenosine Diphosphate; Cardiovascular Diseases; Clopidogrel; Flow Cytometry; Humans; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Prognosis; Pyridines; ROC Curve; Sensitivity and Specificity; Ticlopidine; Treatment Outcome

Patients with type 2 diabetes mellitus (DM) have a markedly increased risk of cardiovascular morbidity and mortality. Guidelines of both the American and Canadian Diabetes Associations recommend the use of aspirin as antiplatelet therapy for all adults with type 2 DM.. The aims of this study were to assess the rate of adherence to guidelines for aspirin use in DM patients in rural Canadian communities and to describe the independent correlates of aspirin use in this population.. We collected information from a cohort of patients with type 2 DM living in 2 rural regions of northern Alberta, Canada, at the time of their enrollment in a multidisciplinary outreach program designed to improve their quality of care. Our primary outcome was self-reported use of antiplatelet therapy (aspirin or others). We use multivariate logistic regression analyses to examine the independent association between sociodemographic and clinical characteristics and self-reported use of antiplatelet agents.. Among 342 patients included in the study (who were typical of rural Canadian patients with type 2 DM), the mean age was 62.9 years; 149 (44%) were men, 84 (25%) were of indigenous origin, and the median time since diagnosis of DM was 8 years. Despite guideline recommendations, only 23% of the cohort (78 patients) were regularly taking aspirin alone or in combination with a thienopyridine (n = 74 and n = 2, respectively) or a thienopyridine alone (n = 2). The results of them ultivariate analyses showed that the only factors independently associated with the use of antiplatelet therapy were symptomatic coronary artery disease (adjusted odds ratio [AOR], 3.1; 95% CI, 1.1-8.7; P=0.033 ), older age (AOR, 2.0 per 10-year interval; 95% CI, 1.7-2.2; P<0.001 ); and male sex (AOR, 1.9; 95% CI, 1.1-3.5; P=0.026 ).. Aspirin is a safe, inexpensive, and readily available therapy that is effective for preventing cardiovascular disease, and patients with type 2 DM are particularly likely to benefit from such preventive therapy. However, we found significant underuse of aspirin therapy among our study population. Aspirin should be included and better promoted as a factor in high-quality, evidence-based DM management.

Topics: Adult; Aged; Aged, 80 and over; Alberta; Aspirin; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug Utilization; Female; Humans; Male; Middle Aged; Patient Compliance; Platelet Aggregation Inhibitors; Pyridines; Rural Population