thienopyridine and Myocardial-Infarction

The study aimed to compare the efficacy and safety outcome associated with a short and a prolonged duration of thienopyridine therapy in patients with chronic kidney disease (CKD) after coronary stenting. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 January 2019 for studies comparing short and prolonged thienopyridine therapy in patients with CKD. Ischemic and bleeding events were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Seven studies comprising a total of 17,628 CKD patients were included in the evaluation. Prolonged duration of thienopyridine use, when compared to short-term thienopyridine, was associated with reduced risk of all-cause mortality (odds ratio 0.75, 95% confidence interval: 0.70-0.81,

Topics: Aged; Coronary Artery Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Pyridines; Renal Insufficiency, Chronic; Risk Assessment; Stents; Stroke; Time Factors

Recent studies have casted a doubt on usefulness of routine glycoprotein IIb/IIIA inhibitors (GPI) in patients, pretreated with aspirin and clopidogrel, undergoing primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI).. We aimed to investigate the effect of relevant factors, particularly thienopyridine pretreatment, on clinical benefit from GPI in randomized controlled trials (RCT).. We searched electronic databases for RCT comparing GPI to control in patients with STEMI undergoing primary PCI. Relevant study covariates and clinical outcomes were extracted. A random effect cumulative and subgroup analyses (thienopyridine non-pretreated studies vs. pretreated studies) were performed. A weighted random effect meta-regression to determine the effect of thienopyridine pretreatment, enrollment year, control group mortality, and ischemic time on mortality benefit from GPI use was conducted.. Twenty studies (9 non-pretreated, 11 pretreated) with a total of 7,414 patients (3,811 GPI, 3,603 control) were included. GPI use reduces mortality (risk ratio, RR = 0.75 95% confidence interval (CI) 0.57-0.97, P = 0.03), target vessel revascularization (TVR) (RR = 0.63, 95% CI 0.50-0.80, P = 0.0002), but not reinfarction (RR = 0.66, 95% CI 0.44-1.0, P = 0.05) at 30 days. There was no effect of thienopyridine pretreatment on reduction in mortality (P = 0.39), reinfarction (P = 0.46), or TVR (P = 0.95) in subgroup analysis. Meta-regression analyses showed significant effect of control group mortality risk (B = -12.15, P = 0.034) but not of thienopyridine pretreatment, enrollment year or control group ischemic time on mortality reduction from GPI use.. The benefit from GPI use in primary PCI for STEMI appears to depend on mortality risk, and not on thienopyridine pretreatment.

Topics: Chi-Square Distribution; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Time Factors; Treatment Outcome

Early studies of glycoprotein IIb/IIIa inhibitors (GPIs) demonstrated benefit during percutaneous coronary intervention for acute coronary syndromes (ACS). Since their introduction, the magnitude of benefit of GPIs has become unclear.. We hypothesized that adding a GPI to unfractionated heparin in ACS patients treated with stents and thienopyridines is beneficial.. We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases for randomized clinical trials that studied the use of GPIs during ACS. We required that patients be randomly assigned to unfractionated heparin plus a GPI versus unfractionated heparin plus placebo (or control). Additional inclusion criteria included the use of coronary stents and periprocedural thienopyridines. Outcomes were assessed at 30 days. Random effects DerSimonian-Laird summary risk ratios (RR) and 95% confidence intervals (CIs) were constructed.. Sixteen studies with 7611 patients were included. Myocardial infarction was 3.1% with GPI versus 4.4% with control (RR = 0.74; 95% CI, 0.59-0.94, P = 0.014); revascularization, 1.7% versus 2.7% (RR = 0.64; 95% CI, 0.46-0.89, P = 0.008); major bleeding, 2.5% versus 2.1% (RR = 1.21; 95% CI, 0.89-1.63, P = 0.22); minor bleeding, 5.5% versus 4.1% (RR = 1.37; 95% CI, 1.06-1.78, P = 0.016); and mortality, 2.2% versus 2.9% (RR = 0.79; 95% CI, 0.59-1.06, P = 0.12), respectively.. Among ACS patients treated with stents and thienopyridines, GPIs were associated with reduced myocardial infarction and revascularization. Minor, but not major bleeding was increased with GPIs. Mortality was similar between the groups. © 2011 Wiley Periodicals, Inc. Supporting information may be found in the online version of this article This work was supported by an unrestricted grant from the Florida Heart Research Institute, which had no role in the study design, data collection, analysis, or interpretation, manuscript writing, or decision to proceed with publication. Anthony A Bavry has received research support from Novartis Pharmaceuticals and serves as a contractor for American College of Cardiology Cardiosource. The other authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Hemorrhage; Heparin; Humans; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Stents

Although studies have demonstrated excess risk of ischemic events if aspirin is withheld preoperatively, it is unclear whether preoperative thienopyridine use influences postoperative outcomes.. We conducted a systematic review of 37 studies (31 cardiac and 6 noncardiac surgery, 3 randomized, 34 observational) comparing postoperative outcomes in patients who were versus were not exposed to thienopyridine in the 5 days before surgery.. Exposure to thienopyridine in the 5 days preceding surgery (compared with no exposure) was not associated with any reduction in postoperative myocardial infarction (23 studies, 12,872 patients, 3.4% vs 3.0%, odds ratio [OR] 0.98; 95% confidence interval [CI], 0.72-1.34), but was associated with increased risks of stroke (16 studies, 10,265 patients, 1.9% vs 1.4%, OR 1.54; 95% CI, 1.08-2.20), reoperation for bleeding (32 studies, 19,423 patients, 4.3% vs 1.8%, OR 2.62; 95% CI, 1.96-3.49), and all-cause mortality (28 studies, 22,990 patients, 3.7% vs 2.6%, OR 1.38; 95% CI, 1.13-1.69). Results were identical when analyses were restricted to long-term users of thienopyridines who continued versus held the medication in the 5 days before surgery. Although all associations were similar in direction for the subset of patients undergoing noncardiac surgery, 97% of the outcome data in this meta-analysis came from cardiac surgery trials.. These data support withholding thienopyridines 5 days before cardiac surgery; there was insufficient evidence to make definitive recommendations for elective noncardiac surgery although the direction and magnitude of associations were similar.

Topics: Contraindications; Humans; Myocardial Infarction; Postoperative Complications; Preoperative Period; Pyridines; Reoperation; Stroke

Coronary stent implantation, particularly drug eluting stents, is now the major method of coronary revascularisation. Following drug-eluting stent implantation dual antiplatelet therapy with aspirin and thienopyridine is recommended for at least 12 months. Premature discontinuation, often at the time of noncardiac surgery, has been associated with stent thrombosis which has a significant risk of death and myocardial infarction. Late (>30 days) and very late (>365 days) stent thrombosis appears to more common with DES and poses the questions of when is it safe to stop antiplatelet therapy post coronary stenting and how to manage patients who need non-cardiac surgery. This article reviews the evidence for stent thrombosis and the peri-operative management of patients with coronary stents and provides an algorithm for patient management based on multidisciplinary assessment of bleeding risk, perioperative cardiac event and stent thrombosis risk.

Topics: Drug-Eluting Stents; Humans; Myocardial Infarction; Myocardial Reperfusion; Perioperative Care; Platelet Aggregation Inhibitors; Pyridines; Risk Factors; Thrombosis; Time Factors

To combine data from all randomized trials of abciximab versus placebo or open-label control in patients with STEMI treated with primary stenting to assess the short-term and long-term mortality, reinfarction, and bleeding complications.. Clinical trials of adjunctive abciximab therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary stenting have produced conflicting results.. Formal searches of electronic databases (Medline, Cochrane) from January 1990 to April 2009 were performed. Five trials randomizing 2,937 patients (1,475 in the abciximab group, 1,462 in the placebo group) were included in the analysis.. When compared with placebo, abciximab was not associated with a significant reduction in the odds of 30-day (OR 0.71, 95% CI: 0.45-1.14, P = 0.16) or long-term (OR 0.85, 95% CI: 0.48-1.50, P = 0.57) mortality. Similarly, the rate of reinfarction was not statistically different at 30 days (OR 0.59, 95% CI: 0.30-1.17, P = 0.13) or at long-term follow-up (OR 0.67; 95% CI: 0.39-1.16, P = 0.16). However, when trials with upstream use of thienopyridines were excluded, abciximab was associated with a significant reduction in the composite of death or reinfarction at 30 days (OR 0.45; 95% CI: 0.26-0.77, P = 0.004) but not at long-term follow-up (OR 0.59; 95% CI: 0.27-1.28, P = 0.18).. Routine use of abciximab in patients with STEMI treated with primary stenting may reduce short-term rates of death or reinfarction in patients not administered preprocedural thienopyridine therapy, but does not appear to be beneficial in those who receive preprocedural thienopyridines.

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Combined Modality Therapy; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Recurrence; Stents

Inhibition of platelet aggregation (IPA) has been a drug development target in acute coronary syndrome (ACS) for almost 2 decades. The relationship between IPA and cardiovascular (CV) events has not been quantified. Cardiovascular (non fatal myocardial infarction, death) and major bleeding events were extracted from phase 2 or 3 randomized, double-blind trials that evaluated oral and intravenous glycoprotein 2b/3a (GP2b/3a) antagonists and thienopyridines. IPA was extracted from different sources that studied a similar regimen in a similar population. Events were correlated to IPA using a linear relative-risk mixed-effects model. Covariates included type of drug, mean age, gender percentage, and ADP. Clinical trial simulations were conducted to evaluate the relationship between IPA and the likelihood of observing a CV event in a 6-month end point trial. Data from 81918 subjects in 20 studies were extracted from the literature. To achieve a 20% relative reduction in CV events would require a further 77% (56%-100%) absolute increase in IPA for IV GP2b/3a antagonists or a further 27%(20%-41%) absolute increase for thienopyridines. CV risk reduction was less in studies with older subjects and greater in studies with greater percentages of male subjects. Assuming a 3% major bleeding rate in the control group, these drugs had a 1% increase in absolute risk as absolute platelet inhibition increases by 60% (range, 40%-80%). This relationship in intrinsic bleeding may be different in different population subtypes. Assuming a 12% event rate, a 6-month active-controlled thienopyridine trial with 3000 subjects could detect a relationship between CV events and IPA with 80% likelihood. Target IPA increases in ACS are an absolute increase of 80% for IV GP2b/3a antagonists and 30% for thienopyridines. Quantitative models using literature data on IPA and CV events can be used to select dose regimens in early stages of drug development.

Topics: Acute Coronary Syndrome; Age Factors; Biomarkers; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Hemorrhage; Humans; Models, Biological; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Sex Factors

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 efficacy of reperfusion therapy, both pharmacological and mechanical, in patients with ST-elevation myocardial infarction (STEMI) is time-dependent. The relation is closer the earlier we are from symptom onset and is valid for thrombolysis within 6h and for primary angioplasty till to at least the twelfth hour. Benefits of reperfusion bring to an advantage both in terms of myocardial salvage and left ventricular systolic function and in terms of quality of life and long-term survival. Although mortality and morbidity of STEMI patients have been greatly reduced in the last 20 years, the need for guideline revision and implementation remains urgent, mostly because mortality of real-world STEMI patients keeps to be always much higher compared to what reported in big randomized controlled trials. The most important indications from big trials and guidelines regarding both pharmacological and non-pharmacological reperfusion strategy in STEMI patients are discussed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Fibrinolytic Agents; Guidelines as Topic; Heparin; Humans; Meta-Analysis as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Quality of Life; Randomized Controlled Trials as Topic; Thrombolytic Therapy; Ticlopidine; Time Factors

Since the development and market entry of clopidogrel, a platelet ADP blocker, physicians have had few new antiplatelet options available to them for the treatment of acute and chronic coronary disease, specifically in the setting of acute coronary syndromes, percutaneous coronary intervention, and chronic stent management. Over the years, limitations of current antiplatelet regimens have emerged, establishing a need for novel antiplatelet drugs. This article discusses potential new targets for platelet inhibition and reviews innovative antiplatelet therapies under investigation.. There are five main categories of antiplatelet therapies currently undergoing clinical study, consisting of the thienopyridines (P2Y12 receptor antagonists), cyclopentyltriazolopyrimidines (P2Y12 receptor antagonists), anti-von Willebrand factor aptamers, thrombin receptor (protease-activated receptor-1) antagonists, and thromboxane receptor antagonists. Early studies of these agents are discussed.. Each of these new antiplatelet therapies has a unique profile that is aimed at improving clinical response with hopes of incremental efficacy and decreased complications, specifically bleeding.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Receptors, Purinergic P2; Receptors, Purinergic P2Y12; Receptors, Thrombin; Ticlopidine; von Willebrand Factor

Antiplatelet therapy to reduce the risks of recurrent myocardial infarction and restenosis after primary percutaneous coronary intervention is critically important to optimize the early treatment of ST-segment elevation myocardial infarction (STEMI). Traditionally, acetylsalicylic acid (ASA; aspirin) has been recommended for patients with suspected STEMI, but this agent targets only one of several pathways of platelet aggregation. Antiplatelet agents with different inhibitory mechanisms may act synergistically with ASA. Glycoprotein IIb/IIIa inhibitors are generally not used with fibrinolytic agents in acute STEMI management; indeed, glycoprotein IIb/IIIa inhibitors plus bolus fibrinolytics increase the risk of intracranial hemorrhage. Aggressive antiplatelet therapy with clopidogrel reduces mortality in STEMI patients and offers significant clinical benefits, without an associated increase in major bleeding events. Recent trials support the development of an early and aggressive approach to more complete platelet inhibition using clopidogrel, in combination with ASA, for patients with STEMI.

Topics: Abciximab; Antibodies, Monoclonal; Aspirin; Clopidogrel; Electrocardiography; Eptifibatide; Fibrinolytic Agents; Humans; Immunoglobulin Fab Fragments; Myocardial Infarction; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Ticlopidine; Tirofiban; Tyrosine

Antiplatelet therapy is the cornerstone of treatment for patients with an acute coronary syndrome (ACS). However, patients presenting with possible ACS are a heterogeneous population, and there is a choice of many potential combination antiplatelet therapies, with aspirin, thienopyridines (eg, clopidogrel), and glycoprotein (GP) IIb/IIIa antagonists. The ISAR-REACT-2 trial investigated the optimal application of triple (aspirin 1 thienopyridine 1 GP IIb/IIIa inhibitor) versus dual (aspirin 1 thienopyridine) antiplatelet therapy for patients with ACS undergoing percutaneous coronary intervention. Abciximab was associated with a significant 25% relative reduction in risk for the 30-day combined endpoint of death, myocardial infarction, or urgent target vessel revascularization. All of this benefit was confined to the patients with elevated troponin levels. The data indicate that troponin can be used as a biomarker to identify patients most likely to benefit from the addition of a GP IIb/IIIa antagonist.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Aspirin; Biomarkers; Blood Platelets; Combined Modality Therapy; Drug Therapy, Combination; Humans; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome; Troponin; Up-Regulation

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

The vast majority of acute coronary syndrome (ACS) trials conducted over the past two decades support the view that women have persistently higher mortality and morbidity despite the introduction of new medical therapies and devices. Even after adjustment for older age, higher prevalence of diabetes, hypertension, heart failure, smaller vessel size, and late presentation, some studies still point to a persistent sex disadvantage. Even in contemporary practice, women continue to have longer delays in presentation and treatment. Selection bias in unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) trials allows inclusion of large numbers of women with clinically insignificant coronary disease and may mistakenly shift results toward apparent benefit of a less aggressive approach. This bias causes further difficulty in determining efficacy and safety of new antithrombotic agents such as direct thrombin inhibitors and glycoprotein IIb/IIa inhibitors across the spectrum of ACS. In trials of UA/NSTEMI, use of objective evidence of ischemia such as elevated troponin levels, would greatly assist the determination of efficacy and benefit in women. Enrollment of more women in clinical trials and timely sex-specific analysis would promote a better understanding of the role of female gender in ACS and would facilitate better care of all patients.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Artery Bypass; Female; Fibrinolytic Agents; Humans; Myocardial Infarction; Myocardial Revascularization; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Stents; Syndrome; Thrombin; Ticlopidine; Women's Health

The recognition that thrombosis is fundamental to acute coronary syndromes (ACS) has inspired the development of novel therapies to inhibit platelet aggregation and thrombus formation. Several recent advances have been made in the management of patients with non-ST-segment elevation ACS (NSTE ACS) to improve early and late clinical outcomes. The research efforts leading to these improvements in care have focused on antiplatelet and anticoagulant therapies coupled with early invasive treatment options. In particular, ongoing clinical trials seek to refine treatment strategies for patients relative to individual risk presentation, the availability of facilities for invasive procedures, and the timing of revascularization. However, even despite the proven efficacy of currently available therapies to reduce the occurrence of death and/or myocardial infarction, still many eligible patients with high-risk NSTE ACS do not receive such treatments. This review provides a pathophysiologic rationale for antithrombotic therapies in ACS, examines the results of recent trials, and presents future directions for clinical investigation.

Topics: Angina, Unstable; Aspirin; Clinical Trials as Topic; Coronary Artery Disease; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Thrombolytic Therapy

Topics: Acute Disease; Angina, Unstable; Anticoagulants; Aspirin; Clinical Trials as Topic; Coronary Disease; Heparin, Low-Molecular-Weight; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Syndrome

Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A2 (TXA2)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with atherosclerotic vascular disease was more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction or vascular death. In the setting of coronary stenting, a double regimen including aspirin and ticlopidine or clopidogrel has proved more effective in the prevention of in-stent thrombosis than aspirin alone. Chronic oral administration of the inhibitors of platelet membrane receptor GP IIb/IIIa has been largely disappointing.

Topics: Aspirin; Benzamidines; Clopidogrel; Coronary Artery Disease; Humans; Myocardial Infarction; Oximes; Piperidines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Stroke; Ticlopidine; Treatment Outcome

Recent advances in our understanding of the role of the platelet in the atherosclerotic process beyond the acute formation of arterial blood clots, such as inflammation, have highlighted the role of antiplatelet agents as being much more than just 'blood thinners.' Some of the most important cardiovascular trials performed in the last 20 years have studied antiplatelet therapies. However, despite their long history, current global health implications and proven benefit, there remain substantial gaps in our understanding as to how to best utilize the limited number of antiplatelet agents available. This article will discuss the mechanism of action of the antiplatelet class known as thienopyridines, the pharmacodynamics and pharmacokinetics of the thienopyridine agent clopidogrel (Plavix, Bristol-Myers Squibb and Sanofi Pharmaceuticals) as well as the literature supporting its clinical benefits and areas of ongoing research that will help clarify the optimal utilization of clopidogrel for the treatment of cardiovascular disease.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Arteriosclerosis; Aspirin; Clinical Trials as Topic; Clopidogrel; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Stents; Ticlopidine; Treatment Outcome; Vascular Diseases

The risk of major adverse cardiac and cerebrovascular events (MACCE) in subjects who interrupt temporarily or permanently thienopyridine therapy in the first 6 months after percutaneous coronary intervention (PCI) remains uncertain. In the dual antiplatelet therapy (DAPT) study subjects were enrolled within 72 hours of PCI and treated with aspirin and a thienopyridine for 12 months before being randomized to continued thienopyridine versus placebo. This analysis focuses on the 12-month period before randomization. Thienopyridine interruptions of greater than 24 hours, occurring in the first 6 months after PCI were evaluated. The incidence of MACCE and moderate or severe bleeding occurring within 12 months after PCI were compared between subjects with and without interruptions. Among 23,002 subjects, the incidence of interruption of thienopyridine was 5.1% (n = 1,173). Compared with subjects who adhered to treatment, subjects with an interruption had a higher incidence of MACCE (6.1% vs 4.3%, p = 0.005), death (2.2% vs 1.4%, p = 0.02), myocardial infarction (3.8% vs 2.7%, p = 0.03), and bleeding (3.1% vs 2.2%, p = 0.04) at 12 months. After adjusting for baseline characteristics, interruptions were associated with MACCE (adjusted odds ratio 1.3, 95% confidence interval 1.0, 1.7, p = 0.04) and had a borderline association with subsequent bleeding (adjusted odds ratio 1.4, 95% confidence interval 1.0, 2.0, p = 0.05). In conclusion, interruption of thienopyridine in the first 6 months after PCI occurs not infrequently and is associated with an increased risk of MACCE and subsequent bleeding between the time of interruption and 12 months after PCI.

Topics: Aged; Aspirin; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Dual Anti-Platelet Therapy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Pyridines; Risk Assessment; Stents; Survival Rate; Time Factors; Treatment Outcome; United States; Withholding Treatment

Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events.. In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models.. In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14).. In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding.

Topics: Aged; Aspirin; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Thrombolytic Therapy

In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in the DAPT study.. Patients were enrolled after coronary stenting, given thienopyridine and aspirin for 12 months, randomly assigned to continued thienopyridine or placebo for an additional 18 months (while taking aspirin), and subsequently treated with aspirin alone for another 3 months. A blinded independent adjudication committee evaluated deaths. Among 11 648 randomized patients, rates of all-cause mortality rates were 1.9 vs. 1.5% (continued thienopyridine vs. placebo, P = 0.07), cardiovascular mortality, 1.0 vs. 1.0% (P = 0.97), and non-cardiovascular mortality, 0.9 vs. 0.5% (P = 0.01) over the randomized period (Months 12-30). Rates of fatal bleeding were 0.2 vs. 0.1% (P = 0.81), and deaths related to any prior bleeding were 0.3 vs. 0.2% (P = 0.36), Months 12-33). Cancer incidence did not differ (2.0 vs. 1.6%, P = 0.12). Cancer-related deaths occurred in 0.6 vs. 0.3% (P = 0.02) and were rarely related to bleeding (0.1 vs. 0, P = 0.25). After excluding those occurring in patients with cancer diagnosed before enrolment, rates were 0.4 vs. 0.3% (P = 0.16).. Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine. Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding. Caution is warranted when considering extended thienopyridine in patients with advanced cancer.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Aspirin; Cause of Death; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Treatment Outcome

The purpose of this study was to characterize outcomes for everolimus-eluting stent (EES)-treated subjects according to treatment with continued thienopyridine plus aspirin versus aspirin alone 12 to 30 months after stenting.. In the DAPT (Dual Antiplatelet Therapy) study, continued thienopyridine plus aspirin beyond 1 year after coronary stenting reduced ischemic events. Given low rates of stent thrombosis and myocardial infarction (MI) for current drug-eluting stents, we examined outcomes among EES-treated subjects in the DAPT study.. The DAPT study enrolled 25,682 subjects (11,308 EES-treated) after coronary stenting. Following 12 months of treatment with thienopyridine and aspirin, eligible subjects continued treatment with aspirin and 9,961 (4,703 with EES) were randomized to 18 months of continued thienopyridine or placebo. Stent type was not randomized, and the EES subset analysis was post hoc.. Among EES-treated patients, continued thienopyridine reduced stent thrombosis (0.3% vs. 0.7%, hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.15 to 0.97; p = 0.04) and MI (2.1% vs. 3.2%, HR: 0.63, 95% CI: 0.44 to 0.91; p = 0.01) versus placebo but did not reduce a composite of death, MI, and stroke (4.3% vs. 4.5%, HR: 0.89, 95% CI: 0.67 to 1.18; p = 0.42), and increased moderate/severe bleeding (2.5% vs. 1.3%, HR: 1.79, 95% CI: 1.15 to 2.80; p = 0.01), and death (2.2% vs. 1.1%, HR: 1.80, 95% CI: 1.11 to 2.92; p = 0.02). Death due to cancer and not related to bleeding was increased (0.64% vs. 0.17%; p = 0.01).. In EES-treated subjects, significant reductions in stent thrombosis and MI and an increase in bleeding were observed with continued thienopyridine beyond 1 year compared with aspirin alone. (The Dual Antiplatelet Therapy Study [DAPT Study]); NCT00977938).

Topics: Aged; Aspirin; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prosthesis Design; Pyridines; Risk Factors; Time Factors; Treatment Outcome

Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis.. After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61).. In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

Topics: Aged; Aspirin; Diabetes Mellitus; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines

Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding.. To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI.. Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014).. Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin.. Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI.. Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.. Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Age Factors; Aged; Antineoplastic Agents, Phytogenic; Aspirin; Diabetes Mellitus; Drug-Eluting Stents; Female; Hemorrhage; Humans; Ischemia; Linear Models; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Risk Assessment; Risk Factors; Smoking; Thrombosis; Time Factors

The DAPT (Dual Antiplatelet Therapy) study enrolled patients after coronary stenting. Patients randomized to continued thienopyridine and aspirin after 12 months had lower ischemic risk but higher bleeding risk than those treated with placebo and aspirin.. This study sought to determine whether a decision tool (DAPT score) aids prescription of dual antiplatelet therapy duration in patients with or without prior myocardial infarction (MI) treated with coronary stents.. Patients were categorized according to any history of MI before the index procedure or no history of MI. Risk differences during the randomized treatment period (12 to 30 months) for ischemic (MI and/or stent thrombosis) and bleeding (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate/severe) events were compared according to DAPT score.. Rates of MI were 3.8% versus 2.4% (p = 0.01) for patients with any MI versus no MI. Continued thienopyridine reduced late MI compared with placebo regardless of MI history (hazard ratio [HR] for any MI: 0.46; p < 0.001; HR for no MI: 0.60; p = 0.003) and increased bleeding (HR: 1.86, p = 0.01 any MI; HR: 1.58, p = 0.01 no MI). DAPT scores ≥2 were associated with reductions in MI/stent thrombosis with continued thienopyridine compared with placebo (2.7% vs. 6.0%, p < 0.001 any MI; 2.6% vs. 5.2%, p = 0.002 no MI), with comparable bleeding rates. Among patients with DAPT scores <2 in both groups, continued thienopyridine was associated with significantly increased bleeding but similar rates of ischemia.. Patients with previous MI have greater risk of late ischemic events than those with no MI history. The DAPT score improves prediction of patient benefit and harm from continued dual antiplatelet therapy beyond assessment of MI history alone. (The Dual Antiplatelet Therapy Study; NCT00977938).

Topics: Aspirin; Decision Support Techniques; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Risk Assessment; Secondary Prevention; Stents; Thrombosis

The TAXUS Liberté Post Approval Study (TL-PAS) contributed patients treated with TAXUS Liberté paclitaxel-eluting stent and prasugrel to the Dual Antiplatelet Therapy Study (DAPT) that compared 12 and 30 months thienopyridine plus aspirin therapy after drug-eluting stents.. Outcomes for 2191 TL-PAS patients enrolled into DAPT were assessed. The DAPT coprimary composite end point (death, myocardial infarction [MI], or stroke) was lower with 30 compared with 12 months prasugrel treatment (3.7% versus 8.8%; hazard ratio [HR], 0.407; P<0.001). Rates of death and stroke were similar between groups, but MI was significantly reduced with prolonged prasugrel treatment (1.9% versus 7.1%; HR, 0.255; P<0.001). The DAPT coprimary end point, stent thrombosis, was also lower with longer therapy (0.2% versus 2.9%; HR, 0.063; P<0.001). MI related to stent thrombosis (0% versus 2.6%; P<0.001) and occurring spontaneously (1.9% versus 4.5%; HR, 0.407; P=0.007) were both reduced with prolonged prasugrel. MI rates increased within 90 days of prasugrel cessation after both 12 and 30 months treatment. Composite Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) moderate or severe bleeds were modestly increased (2.4% versus 1.7%; HR, 1.438; P=0.234) but severe bleeds were not more frequent (0.3% versus 0.5%; HR, 0.549; P=0.471) in the prolonged treatment group.. Prasugrel and aspirin continued for 30 months reduced ischemic events for the TAXUS Liberté paclitaxel-eluting stent patient subset from DAPT through reductions in MI and stent thrombosis. Withdrawal of prasugrel was followed by an increase in MI after both 12 and 30 months therapy. The optimal duration of dual antiplatelet therapy with prasugrel after TAXUS Liberté paclitaxel-eluting stent remains unknown, but appears to be >30 months.. http://www.clinicaltrials.gov. Unique identifier: NCT00997503.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Coronary Disease; Double-Blind Method; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Incidence; Internationality; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Pyridines; Thiophenes; Time Factors; Treatment Outcome

The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations.. This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI.. The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding.. Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21).. Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938).

Topics: Aspirin; Double-Blind Method; Female; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Pyridines; Risk Assessment; Stents; Thrombosis; Time Factors

Vorapaxar antagonizes protease-activated receptor 1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use.. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with previous atherothrombosis. This prespecified analysis included 16,897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI, and stroke in comparison with placebo regardless of planned thienopyridine therapy (planned thienopyridine, hazard ratio, 0.80, 0.70-0.91, P<0.001; no planned thienopyridine, hazard ratio, 0.75; 0.60-0.94, P=0.011; P-interaction=0.67). Findings were similar when patients were stratified by actual thienopyridine use at baseline (P-interaction=0.82) and through 18 months (P-interaction=0.44). Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned, hazard ratio, 1.50; 1.18-1.89, P<0.001; no planned, hazard ratio, 1.90, 1.17-3.07, P=0.009; P-interaction=0.37) or actual thienopyridine use (P-interaction=0.24).. Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of previous MI, whether treated concomitantly with a thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of thienopyridine use.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474.

Topics: Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Internationality; Ischemic Attack, Transient; Lactones; Male; Middle Aged; Myocardial Infarction; Pyridines; Receptor, PAR-1; Receptors, Thrombin; Secondary Prevention; Stroke; Treatment Outcome

We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients.. In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10).. Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Double-Blind Method; Embolism; Female; Humans; Kaplan-Meier Estimate; Male; Morpholines; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Rivaroxaban; Stroke; Thiophenes; Ticlopidine; Treatment Outcome; Warfarin

In randomized trials, low-dose (LD) and high-dose (HD) aspirin (ASA) are equally effective in reducing ischemic complications, but HD ASA is associated with an increased risk of bleeding in the setting of dual antiplatelet therapy after percutaneous coronary intervention (PCI). ASA dose after PCI varies across countries, but little is known about variation within the United States (US) and whether this variation can be explained by clinical characteristics of patients. We used enrollment data from the Dual Antiplatelet Therapy Study, a randomized trial designed to compare 12 versus 30 months of dual antiplatelet therapy after PCI, to quantify the variation in ASA dosing after PCI in the US subjects and assess the extent to which dose variability was attributable to patient characteristics. Of the 23,336 patients enrolled in the US, 28.0% were prescribed LD ASA at discharge after PCI. Patient characteristics explained 1.6% of total variance in ASA dose, whereas the study site accounted for 45.9% of the unexplained variability. The median odds ratio comparing sites was 5.05 (95% confidence interval 4.29 to 5.85), which was greater than any individual predictor of ASA dose. In conclusion, LD ASA after PCI in the US was used in a minority of patients, and heterogeneity in its selection was mainly influenced by the site of enrollment rather than patient characteristics. As HD ASA may be associated with adverse events in the setting of dual antiplatelet therapy, reducing local practice variation in the dose of ASA may be a target for quality improvement.

Topics: Aspirin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Period; Pyridines; Retrospective Studies; Stents; Treatment Outcome

The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) is not known. Factors influencing DAPT duration are not well described.. We hypothesized that continued DAPT 12 months beyond ACS would be associated with patient factors such as stent type and that it may be associated with lower rates of ischemic events.. The TIMI 38 Coronary Stent Registry (CSR) followed patients who completed the TRITON-TIMI 38 trial, received a stent, and were alive and event free. Continuation of DAPT was determined by the treating physician.. The CSR enrolled 2110 patients (1679>12 months from index ACS) and followed for a median of 2.1 additional years. DAPT was continued in 554 (26%) and was more likely to be continued in patients with drug-eluting stents (DES; 54%) and in North America. The rate of cardiovascular death, MI, or stroke was 2.35% per year, and 13 patients (0.6%) experienced Academic Research Consortium definite or probable ST. Recurrent ischemic events were similar between patients who continued thienopyridine therapy and those who stopped at registry entry (P = 0.74 for cardiovascular death/MI/stroke; P = 0.72 for definite or probable ST). After propensity score adjustment, there was no significant difference in cardiovascular death/MI/stroke (P = 0.55) or bleeding (P = 0.51) with prolonged DAPT.. Patients stabilized for a year after ACS and stenting have low rates of ST relative to overall cardiovascular events. The decision to continue DAPT maybe associated with stent type (DES vs bare-metal stent) and region.

Topics: Acute Coronary Syndrome; Aged; Combined Modality Therapy; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Pyridines; Registries; Stents; Stroke; Survival Analysis; Treatment Outcome

Rates of stent thrombosis (ST) after ST-elevation myocardial infarction (STEMI) may vary over time and the relationship of this complication with non-adherence to dual antiplatelet therapy (DAPT) during long-term follow-up remains unclear.. We analysed 2,997 patients who were treated with at least one stent and in whom a non-target vessel ST did not occur during follow-up from the large-scale Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial of patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Aspirin was prescribed indefinitely, and a thienopyridine for at least six months. DAPT usage was evaluated according to the development of ST in four time periods (<1 month, 1-6 months, 6-12 months and >1 year from index stent implantation). DAPT non-usage was lowest within the first month, but was strongly associated with ST. During the 1-6 month period the relationship remained strong, but was absent in the 6-12 month period. Beyond one year, ST was associated with non-usage of aspirin but was paradoxically more common in patients taking a thienopyridine.. The relationship between stent thrombosis and non-adherence to DAPT varies over time. It is strong within the first month, remains important until six-month follow-up but fades afterwards. Very late ST is associated with both DAPT and aspirin alone but not with thienopyridine non-adherence.

Topics: Aspirin; Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Patient Compliance; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Surveys and Questionnaires; Treatment Outcome

In the setting of ST-segment elevation myocardial infarction (STEMI), patients at high risk of systemic emboli who undergo primary percutaneous coronary intervention (PCI) using stents might require triple antithrombotic therapy (a combination of aspirin, thienopyridine, and vitamin K antagonist [VKA]). The risks and benefits of such therapy in the setting of STEMI have been incompletely characterized. We, therefore, assessed the outcomes of patients who received triple therapy after primary PCI in the large-scale, contemporary Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI] trial. Among the 3,320 patients triaged to primary PCI, 126 (3.8%) were prescribed triple therapy and 3,194 (96.2%) were prescribed dual antiplatelet therapy. The most frequent indications for VKA treatment were a severely reduced left ventricular ejection fraction with a large akinetic area, atrial fibrillation (23.8% each), and mural thrombus (23.0%). The assignment to triple therapy was associated with older age, female gender, rhythm disturbances, Killip class > 1 on admission, lower left ventricular ejection fraction, left anterior descending artery territory infarcts, and Final Thrombolysis In Myocardial Infarction flow grade < 3. Patients treated with triple versus dual therapy had comparable short- and long-term ischemic outcomes but had significantly increased rates of major bleeding during the index hospitalization (17.1% vs 6.5%, p < 0.0001), resulting in premature VKA discontinuation in 14.3% of those patients. In conclusion, in the setting of STEMI treated with primary PCI, the combination of aspirin, thienopyridine, and VKA results in an excess of bleeding complications and premature discontinuation of VKA. The risk of adding oral anticoagulation to patients admitted for STEMI should be carefully considered before choosing drug-eluting or bare metal stents.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Coronary Angiography; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Electrocardiography; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Postoperative Period; Prospective Studies; Pyridines; Treatment Outcome

Patients' responses to oral antiplatelet therapy are subject to variation. Bedside monitoring offers the opportunity to improve outcomes after coronary stenting by individualizing therapy.. We randomly assigned 2440 patients scheduled for coronary stenting at 38 centers to a strategy of platelet-function monitoring, with drug adjustment in patients who had a poor response to antiplatelet therapy, or to a conventional strategy without monitoring and drug adjustment. The primary end point was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization 1 year after stent implantation. For patients in the monitoring group, the VerifyNow P2Y12 and aspirin point-of-care assays were used in the catheterization laboratory before stent implantation and in the outpatient clinic 2 to 4 weeks later.. In the monitoring group, high platelet reactivity in patients taking clopidogrel (34.5% of patients) or aspirin (7.6%) led to the administration of an additional bolus of clopidogrel, prasugrel, or aspirin along with glycoprotein IIb/IIIa inhibitors during the procedure. The primary end point occurred in 34.6% of the patients in the monitoring group, as compared with 31.1% of those in the conventional-treatment group (hazard ratio, 1.13; 95% confidence interval [CI], 0.98 to 1.29; P=0.10). The main secondary end point, stent thrombosis or any urgent revascularization, occurred in 4.9% of the patients in the monitoring group and 4.6% of those in the conventional-treatment group (hazard ratio, 1.06; 95% CI, 0.74 to 1.52; P=0.77). The rate of major bleeding events did not differ significantly between groups.. This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

Topics: Aged; Aspirin; Clopidogrel; Coronary Disease; Coronary Thrombosis; Drug Monitoring; Female; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Point-of-Care Systems; Prasugrel Hydrochloride; Pyridines; Retreatment; Stents; Thiophenes; Ticlopidine

We assessed the impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention using alternative antithrombotic regimens and stent types. In the HORIZONS-AMI trial 3,602 patients were randomly assigned to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) or bivalirudin alone and paclitaxel-eluting stents or bare-metal stents. Compared to nonsmokers, smokers had significantly lower rates of mortality and major bleeding at 30 days and at 1 year; however, the differences were no longer significant after covariate adjustment. Smoking was associated with increased rates of definite/probable stent thrombosis (ST) at 1 year (adjusted RR 1.99, 95% confidence interval 1.28 to 3.10) mainly because of a higher rate of late ST after paclitaxel-eluting stent implantation (1.9% vs 0.4%, p = 0.0006). In smokers bivalirudin monotherapy compared to UFH plus a GPI was associated with lower mortality at 30 days (0.5% vs 2.2%, p = 0.002) and at 1 year (1.8% vs 4.0%, p = 0.008). No decrease in mortality was seen with bivalirudin in nonsmokers. Major bleeding was significantly decreased with bivalirudin regardless of smoking status (smokers 3.7% vs 8.9%, p <0.0001; nonsmokers 6.5% vs 9.6%, p = 0.01). In conclusion, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, smoking is an independent predictor of definite/probable ST at 1 year. Bivalirudin monotherapy compared to UFH plus a GPI decreased major bleeding regardless of smoking status but may have different effects on individual components of ischemic events.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug Utilization; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Recombinant Proteins; Smoking; Stents

The impact of thienopyridine administration prior to primary stenting in acute myocardial infarction (AMI) has not been well studied. We therefore examined the database from the prospective, multicenter, controlled CADILLAC trial in which 1,036 patients were randomized to bare metal stenting with or without abciximab to determine whether patients who received a thienopyridine prior to bare metal stenting in AMI had superior clinical outcomes. Per operator discretion, 659 patients (63.6%; Th+) received either a 500 mg ticlopidine loading dose (n = 623) or a 300 mg clopidogrel loading dose (n = 40), while 377 patients (36.4%; Th-) received no thienopyridine prior to stent implantation. Baseline and procedural characteristics of the two groups, including abciximab use (52.5% vs 52.8%, P = 0.93) were well matched. Th+ compared to Th- patients had lower rates of core lab assessed TIMI 0/1 flow postprocedure (0.8% vs 2.7%, P = 0.01). Th+ compared to Th- patients also had significantly reduced in-hospital and 30-day rates of ischemic target vessel revascularization (TVR) (1.1% vs 3.2%, P = 0.01 and 1.5% vs 3.8%, P = 0.02, respectively) and major adverse cardiovascular events (MACE) (2.7% vs 5.8%, P = 0.01 and 4.0% vs 6.9%, P = 0.03, respectively), results that remained significant after covariate adjustment. In conclusion, in this large prospective, controlled trial, patients receiving a thienopyridine prior to primary stenting in AMI were less likely to have TIMI 0/1 flow postprocedure and experienced reduced in-hospital and 30-day rates of ischemic TVR and MACE compared to those not administered a thienopyridine prior to stent implantation.

Topics: Abciximab; Aged; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Aspirin; Confidence Intervals; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Immunoglobulin Fab Fragments; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Revascularization; Odds Ratio; Platelet Aggregation Inhibitors; Preoperative Care; Pyridines; Time Factors

Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen.. In this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5-20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00402597.. Three patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2.21 [95% CI 1.25-3.91] for 5 mg, 3.35 [2.31-4.87] for 10 mg, 3.60 [2.32-5.58] for 15 mg, and 5.06 [3.45-7.42] for 20 mg doses; p<0.0001). Rates of the primary efficacy endpoint were 5.6% (126/2331) for rivaroxaban versus 7.0% (79/1160) for placebo (HR 0.79 [0.60-1.05], p=0.10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3.9%] vs 62/1160 [5.5%]; HR 0.69, [95% CI 0.50-0.96], p=0.0270). The most common adverse event in both groups was chest pain (248/2309 [10.7%] vs 118/1153 [10.2%]).. The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway.. Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG.

Topics: Acute Coronary Syndrome; Administration, Oral; Aspirin; Chest Pain; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Myocardial Infarction; Proportional Hazards Models; Pyridines; Recurrence; Risk Reduction Behavior; Rivaroxaban; Safety; Statistics, Nonparametric; Stroke; Thiophenes; Treatment Outcome

This analysis sought to investigate the complementary effect of thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin blockade in coronary stent intervention.. Definitive evidence supporting combined antiplatelet therapy consisting of thienopyridine pretreatment and GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is limited.. We retrospectively analyzed clinical outcomes by thienopyridine use in the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the ESPRIT trial.. A total of 901 patients received a loading dose of thienopyridine before PCI (group 1), 123 received thienopyridine pretreatment without a loading dose (group 2), and 1,016 were not treated with thienopyridine before PCI (group 3). The composite incidence of death or myocardial infarction at 30 days was significantly lower in group 1 than in groups 2 and 3 combined (OR, 0.71 [95%CI, 0.52-0.99]; P = 0.0417). A similar trend was seen for the composite of death, myocardial infarction, or urgent target vessel revascularization (unadjusted OR, 0.77 [0.57-1.05]; P = 0.1025). After adjusting for baseline characteristics, these differences were no longer significant. No interactions were identified with eptifibatide assignment for any of the group comparisons.. Pretreatment with a loading dose of thienopyridine lowers the rate of ischemic complications regardless of treatment with a GP IIb/IIIa inhibitor. Conversely, the efficacy of eptifibatide is maintained whether or not a loading dose of a thienopyridine is administered. Optimal outcomes are achieved in patients receiving thienopyridine pretreatment along with platelet GP IIb/IIIa inhibitor therapy.

Topics: Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Drug Administration Schedule; Drug Therapy, Combination; Eptifibatide; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Retrospective Studies; Risk Assessment; Stents; Ticlopidine; Time Factors; Treatment Outcome

Biological age is a strong determinant of prognosis in patients with acute myocardial infarction (AMI). We sought to examine the impact of age after primary percutaneous coronary intervention in AMI and to determine whether routine coronary stent implantation and/or platelet glycoprotein IIb/IIIa inhibitors improve clinical outcomes in elderly patients after primary angioplasty.. In the CADILLAC trial, 2082 patients with AMI were randomized to balloon angioplasty, angioplasty plus abciximab, stenting alone, or stenting plus abciximab. No patient was excluded on the basis of advanced age; patients ranging from 21 to 95 years of age were enrolled. One-year mortality increased for each decile of age, exponentially after 65 years of age (1.6% for patients <55 years, 2.1% for 55 to 65 years, 7.1% for 65 to 75 years, 11.1% for patients >75 years; P<0.0001). Elderly patients also had increased rates of stroke and major bleeding compared with their younger counterparts. Among elderly patients (> or =65 years), 1-year rates of ischemic target revascularization (7.0% versus 17.6%; P<0.0001) and subacute or late thrombosis (0% versus 2.2%; P=0.005) were reduced with stenting compared with balloon angioplasty. Routine abciximab administration, although safe, was not of definite benefit in elderly patients. Rates of mortality, reinfarction, disabling stroke, and major bleeding in the elderly were independent of reperfusion modality.. Despite contemporary mechanical reperfusion strategies, mortality, major bleeding, and stroke rates remain high in elderly patients undergoing primary percutaneous coronary intervention, outcomes that are not affected by stents or glycoprotein IIb/IIIa inhibitors. By reducing restenosis, however, stent implantation improves clinical outcomes in elderly patients with AMI.

Topics: Abciximab; Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Aspirin; Cohort Studies; Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Female; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Life Tables; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pyridines; Stents; Stroke; Treatment Outcome

Stent fracture (SF) and peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation are considered to be related to very late stent thrombosis (VLST). How dual antiplatelet therapy (DAPT) beyond 1 year affects the clinical outcomes of patients with SF or PSS remains unclear.Methods and Results:Based on their DAPT status, 1,962 patients undergoing SES implantation were classified as on-thienopyridine (n=1,404) or off-thienopyridine (n=558). The 6-year incidence of VLST was significantly lower in the on-thienopyridine patients (0.56% vs. 1.8%, P=0.01), whereas cardiac death and myocardial infarction (MI) were similar (5.0% vs. 6.2%, P=0.31; 3.2% vs. 4.0%, P=0.33; respectively). The 1,962 patients were also classified as having SF/PSS (n=256) or non-SF/PSS (n=1,706). In the SF/PSS group, VLST and MI were significantly lower in on-thienopyridine patients (1.9% vs. 10.1%, P=0.003; 3.5% vs. 10.3%, P=0.02; respectively). In the non-SF/PSS group, VLST and MI were similar (0.36% vs. 0.45%, P=0.78; 3.2% vs. 3.0%, P=0.93; respectively). In both groups, cardiac death was similar (3.6% vs. 4.3%, P=0.78; 5.2% vs. 6.5%, P=0.32; respectively).. Prolonged DAPT was associated with significantly lower incidences of VLST and MI in the SF/PSS group, but had no effect on cardiac death, VLST, or MI in the non-SF/PSS group.

Topics: Aged; Aspirin; Death; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prosthesis Implantation; Pyridines; Retrospective Studies; Sirolimus; Staining and Labeling; Thrombosis; Time Factors; Treatment Outcome

Early cardiovascular and bleeding events after coronary stenting are associated with high risk of morbidity and mortality.. To assess the prognosis of cardiovascular and bleeding events occurring beyond 1 year after coronary stenting.. This secondary analysis is derived from data from the Dual Antiplatelet Therapy (DAPT) Study, a multicenter trial involving 220 US and international clinical sites from 11 countries. The study dates were August 2009 to May 2014. Individuals who underwent coronary stenting and completed 12 months of thienopyridine plus aspirin therapy without ischemic or bleeding events remained on an aspirin regimen and were randomized to continued thienopyridine therapy vs placebo for 18 additional months. Individuals were then followed up for 3 additional months while receiving aspirin therapy alone. The analysis began in August 2015.. Ischemic events (myocardial infarction not related to stent thrombosis, stent thrombosis, and ischemic stroke) and bleeding events (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries [GUSTO] classification moderate or severe bleeding).. Ischemic events (myocardial infarction not related to stent thrombosis, stent thrombosis, and ischemic stroke) and bleeding events (GUSTO classification moderate or severe bleeding). Death at 21 months after randomization (33 months after coronary stenting).. In total, 25 682 individuals older than 18 years with an indication for coronary stenting were enrolled, and 11 648 (mean age, 61.3 years; 25.1% female) were randomized. After randomization, 478 individuals (4.1%) had 502 ischemic events (306 with myocardial infarction, 113 with stent thrombosis, and 83 with ischemic stroke), and 232 individuals (2.0%) had 235 bleeding events (155 with moderate and 80 with severe bleeding). Among individuals with ischemic events, 52 (10.9%) died. The annualized mortality rate after an ischemic event was 27.2 (95% CI, 20.3-35.7) per 100 person-years. The cumulative incidence of death after an ischemic event among the total randomized study population was 0.5% (0.3% with myocardial infarction, 0.1% with stent thrombosis, and 0.1% with ischemic stroke). Among individuals with bleeding events, 41 (17.7%) died. The annualized mortality rate after a bleeding event was 21.5 (95% CI, 15.4-29.1) per 100 person-years. The cumulative incidence of death after a bleeding event among the total randomized study population was 0.3% (0.1% with moderate and 0.2% with severe bleeding).. In patients treated with dual antiplatelet therapy for at least 1 year after coronary stenting, ischemic events were more frequent than bleeding events, and both events were associated with high risk of mortality.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Aged; Aspirin; Brain Ischemia; Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Pyridines; Stents; Stroke

The role of triple antithrombotic therapy vs dual antithrombotic therapy in patients with both atrial fibrillation and coronary artery disease remains unclear. This study explores the differences in treatment practices and outcomes between triple antithrombotic therapy and dual antithrombotic therapy in patients with atrial fibrillation and coronary artery disease.. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (n = 10,135), we analyzed outcomes in patients with coronary artery disease (n = 1827) according to treatment with triple antithrombotic therapy (defined as concurrent therapy with an oral anticoagulant, a thienopyridine, and aspirin) or dual antithrombotic therapy (comprising either an oral anticoagulant and one antiplatelet agent [OAC plus AA] or 2 antiplatelet drugs and no anticoagulant [DAP]).. The use of triple antithrombotic therapy, OAC plus AA, and DAP at baseline was 8.5% (n = 155), 80.4% (n = 1468), and 11.2% (n = 204), respectively. Among patients treated with OAC plus AA, aspirin was the most common antiplatelet agent used (90%), followed by clopidogrel (10%) and prasugrel (0.1%). The use of triple antithrombotic therapy was not affected by patient risk of either stroke or bleeding. Patients treated with triple antithrombotic therapy at baseline were hospitalized for all causes (including cardiovascular) more often than patients on OAC plus AA (adjusted hazard ratio 1.75; 95% confidence interval, 1.35-2.26; P <.0001) or DAP (hazard ratio 1.82; 95% confidence interval, 1.25-2.65; P = .0018). Rates of major bleeding or a combined cardiovascular outcome were not significantly different by treatment group.. Choice of antithrombotic therapy in patients with atrial fibrillation and coronary artery disease was not affected by patient stroke or bleeding risks. Triple antithrombotic therapy-treated patients were more likely to be hospitalized for all causes than those on OAC plus AA or on DAP.

Topics: Administration, Oral; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hospitalization; Humans; Male; Markov Chains; Monte Carlo Method; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pyridines; Registries; Stroke; Ticlopidine; Warfarin

The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation.. A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs.. The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group.. In AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chi-Square Distribution; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Pyridines; Republic of Korea; Retrospective Studies; Risk Factors; Stents; Time Factors; Treatment Outcome; Warfarin

Timely and appropriate use of antiplatelet and anticoagulant therapies has been shown to improve outcomes among ST-segment elevation myocardial infarction (STEMI) patients but has not been well described in patients transferred for primary percutaneous coronary intervention (PCI).. We examined 16,801 (26%) transfer and 47,329 direct-arrival STEMI patients treated with primary PCI at 441 Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines hospitals. Medication use was compared between transfer and direct-arrival patients to determine if these therapies were delayed or dosed in excess.. Although transfer patients were more likely to receive antiplatelet and anticoagulant therapies before catheterization, they had longer delays to initiation of heparin (35 vs. 25 minutes), clopidogrel (119 vs. 84 minutes), and glycoprotein IIb/IIIa inhibitor (107 vs. 60 minutes, P < .0001 for both). Administration of low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitor at the STEMI-referring hospital was associated with longer delays to reperfusion compared with deferred administration at the STEMI-receiving hospital, whereas early use of unfractionated heparin was not. Among treated patients, those transferred were more likely to receive excess heparin dosing (adjusted odds ratio [OR] 1.28 [95% CI 1.04-1.58] for unfractionated heparin, adjusted OR 1.54 [95% CI 1.09-2.18] for low-molecular-weight heparin) and are associated with higher risks of major bleeding complications (adjusted OR 1.10, 95% CI 1.03-1.17).. ST-segment elevation myocardial infarction patients transferred for primary PCI in community practice are at risk for delayed and excessively dosed antithrombotic therapy, highlighting the need for continued quality improvement to maximize the appropriate use of these important adjunctive therapies.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Cohort Studies; Early Medical Intervention; Female; Guideline Adherence; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Male; Middle Aged; Myocardial Infarction; Patient Transfer; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Practice Guidelines as Topic; Pyridines; Recombinant Proteins; Retrospective Studies; Ticlopidine; Time-to-Treatment

Topics: Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic

Although previous retrospective studies have suggested the clinical benefits of clopidogrel pretreatment in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the antiplatelet effect of thienopyridines during a narrow door-to-balloon time frame has not been evaluated. Seventy-nine consecutive patients with STEMI were treated with either 600 mg of clopidogrel (n = 49) or 60 mg of prasugrel (n = 30) loading on admission. All patients underwent PPCI with a door-to-balloon time of 48 ± 20 minutes. Adenosine diphosphate (ADP)-induced platelet aggregation (PA) was determined by light transmission aggregometry before thienopyridine loading, at PPCI, and after 72 hours. Baseline ADP-induced PA was comparable in clopidogrel- and prasugrel-treated patients (79 ± 10% vs 76 ± 9%, p = 0.2). Although ADP-induced PA was reduced significantly in both clopidogrel- and prasugrel-treated patients (p <0.01 for both), it was significantly lesser in prasugrel-treated patients (63 ± 18% vs 74 ± 12%, p = 0.002). Yet, <50% of the prasugrel-treated patients achieved adequate platelet inhibition (ADP-induced PA <70%) at PPCI. Prasugrel-treated patients, compared with clopidogrel-treated patients, were more likely to have Thrombolysis In Myocardial Infarction myocardial perfusion grade of ≥2 (79% vs 49%, p = 0.01), lower Thrombolysis In Myocardial Infarction frame count (10.2 ± 5.7 vs 13.6 ± 7.2, p = 0.03), and a numerically greater incidence of early ST-segment resolution >50% (26 of 30 [87%] vs 35 of 49 [71%], p = 0.1), suggesting better myocardial reperfusion. In conclusion, overall, prasugrel compared with clopidogrel pretreatment resulted in greater platelet inhibition at PPCI, but even with prasugrel, only <50% of the patients achieved early adequate platelet response.

Topics: Clopidogrel; Coronary Angiography; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Pyridines; Thiophenes; Ticlopidine; Treatment Outcome

Optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has not been yet fully elucidated.. We assessed the influence of prolonged thienopyridine therapy on clinical outcomes with landmark analysis at 4 and 13 months after DES implantation. Among 6802 patients with at least 1 DES implantation in the CREDO-Kyoto Registry Cohort-2, 6309 patients (on thienopyridine, 5438 patients; off thienopyridine, 871 patients) and 5901 patients (on thienopyridine, 4098 patients; off thienopyridine, 1803 patients) were eligible for the 4- and 13-month landmark analyses, respectively. The majority of patients had stable coronary artery disease (73%) and received sirolimus-eluting stents (93%), and approximately 90% of thienopyridine was ticlopidine. Patients taking thienopyridine had more complex comorbidities and more complex lesion and procedural characteristics as compared with patients not taking thienopyridine. After adjusting for confounders, thienopyridine use was not associated with decreased risk for death/myocardial infarction/stroke (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.89-1.43, P=0.32 in the 4-month landmark analysis; HR, 1.14; 95% CI, 0.90-1.45, P=0.29 in the 13-month landmark analysis, respectively), whereas the risk for GUSTO moderate/severe bleeding tended to be higher in patients taking thienopyridine (HR, 1.51; 95% CI, 1.00-2.23, P=0.049 in the 4-month landmark analysis; HR, 1.44; 95% CI, 0.99-2.09, P=0.057 in the 13-month landmark analysis, respectively).. Prolonged thienopyridine therapy beyond 4 and 13 months appeared not to be associated with reduction in ischemic events but to be associated with a trend toward increased bleeding. Optimal duration of DAPT after DES implantation might be shorter than the currently recommended 1-year interval.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Chi-Square Distribution; Clopidogrel; Cohort Studies; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prosthesis Design; Pyridines; Registries; Stroke; Ticlopidine; Time Factors; Treatment Outcome

We sought to identify patients at risk for premature discontinuation of thienopyridines and to develop a risk score for thienopyridine adherence after coronary stent implantation. Patients were prospectively included from December 2007 to March 2008. At 1-month follow-up, all patients were given the Morisky questionnaire and asked if they had stopped taking thienopyridines. Multivariate analysis identified predictors of thienopyridine discontinuation; points were assigned to each variable according to the odds ratios and the c-statistic of the score was calculated. Mean age of the 400 patients included was 61.0 ± 10.4 years; 66 patients (16.5%) stopped thienopyridines after 1 month. Reasons for discontinuation were cost (62%), lack of information (17%), and recommendation by another doctor to stop treatment (15%). Factors associated with discontinuation included unmarried status (odds ratio 2.48, p = 0.046), lack of private health insurance (odds ratio 4.68, p = 0.041), acute coronary syndrome (odds ratio 2.31, p = 0.004), nondiabetics (odds ratio 2.20, p = 0.041), and patients who earned <2 times (odds ratio 8.23, p <0.001) and 2 to 3 times (odds ratio 4.46, p = 0.021) the minimum wage. Total risk score was 0 to 14 points and was strongly associated with thienopyridine discontinuation. For total scores of 0 to 4, 5 to 8, 9 to 12, and ≥13, 0%, 7%, 20%, and 37% of patients, respectively, stopped thienopyridines (c-statistic 0.76, p <0.0001). Risk score was also significantly associated with complete adherence as assessed by the Morisky questionnaire (c-statistic 0.74, p <0.001). In conclusion, we have identified patients at risk for premature discontinuation of thienopyridines using variables obtained before stent implantation and developed a risk score that accurately predicts premature thienopyridine discontinuation.

Topics: Acute Coronary Syndrome; Brazil; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Compliance; Postoperative Care; Prospective Studies; Pyridines; Risk Assessment; Risk Factors; Stents; Surveys and Questionnaires; Treatment Refusal

Topics: Adrenergic beta-Antagonists; Angiography; Angioplasty, Balloon, Coronary; Anticoagulants; Contrast Media; Electrocardiography; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Pyridines; Stents

Practice guidelines reflect a consensus of expert opinion for patient care after a thorough review of clinical trials relevant to a given patient population. However, in keeping pace with the influx of new data, these recommendations need to be revised periodically to remain current. The American College of Cardiology (ACC) and the American Heart Association (AHA) published the Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction in 2004 and the Guidelines for Percutaneous Coronary Intervention in 2005 with their respective Focused Updates in 2007. Now, 2 years later, further revision of these guidelines has been published as Focused Updates of 2009.

Topics: American Heart Association; Angioplasty, Balloon, Coronary; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; United States

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Drug Therapy, Combination; Drug-Eluting Stents; Electrocardiography; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Myocardial Infarction; Myocardial Revascularization; Odds Ratio; Peptic Ulcer; Platelet Aggregation Inhibitors; Prognosis; Proton Pump Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Ticlopidine; Time Factors

To investigate how thienopyridine treatment, with or without associated fibrinolysis, affects the rates of major bleeding and inhospital death in patients with ST-elevation myocardial infarction (STEMI).. The rates of major bleeding and in-hospital death were studied in 14,259 consecutive patients with STEMI. During hospitalization, 5340 (38%) received thienopyridines, 3007 (21%) received fibrinolytic drugs, and 2044 (14%) received both.. Major bleeding occurred more frequently in patients who received thienopyridines with or without fibrinolytics, in 4.6% and 4.1%, respectively, compared with 2.3% in those who received fibrinolytics alone and 2.8% in those who received neither (P< .001). Multivariate analysis, which included adjustments for risk factors for bleeding, percutaneous coronary intervention and cardiac catheterization, showed that thienopyridine treatment was an independent risk factor for bleeding (odds ratio=1.68; 95% confidence interval, 1.23-2.31). In-hospital mortality was lower in patients who received a thienopyridine, and such treatment was an independent predictor of lower mortality (odds ratio=0.50; 95% confidence interval, 0.39-0.60).. Thienopyridine treatment was associated with an increased risk of major bleeding but also with a better in-hospital prognosis. These findings in unselected patients with STEMI, who are representative of those seen in daily clinical practice, complement, but do not replace, the data obtained in randomized clinical trails of selected patients.

Topics: Acute Disease; Aged; Aged, 80 and over; Coronary Disease; Electrocardiography; Endpoint Determination; Female; Fibrinolytic Agents; Hemorrhage; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Pyridines; Registries

Topics: Adenosine; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Cost-Benefit Analysis; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Prognosis; Purinergic P2 Receptor Antagonists; Pyridines; Risk Assessment; Survival Rate; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

A 56-year-old male was admitted for elective percutaneous coronary intervention. Four days later he developed subacute stent thrombosis in the proximal stent in his right coronary artery. Using the Multiplate(R) ASPI and ADP test, we detected combined aspirin and clopidogrel resistance. The doses of aspirin and clopidogrel were increased to 300 mg and 150 mg, respectively. This resulted with optimization of aspirin response, but clopidogrel resistance was doseindependent. Three days later, the patient developed a new episode of ST-elevation myocardial infarction due to recurrent subacute thrombosis in the proximal stent. Consequently, clopidogrel was switched to ticlopidine 250 mg twice daily with resultant optimal platelet inhibition in the ADP test and the patient became clinically stable. This case indicates the clinical benefit from routine assessment of platelet responsiveness to antiaggregation therapy in patients with stent thrombosis. Also, clopidogrel resistance is drug-specific and not necessarily a class-effect phenomenon. By modifying drugs' doses, type of thienopyridine, or both, we can optimize antiplatelet therapy and the clinical course.

Topics: Angioplasty, Balloon, Coronary; Clopidogrel; Coronary Thrombosis; Drug Resistance; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Secondary Prevention; Stents; Ticlopidine

Twelve months of uninterrupted thienopyridine therapy after drug-eluting stents (DES) implantation was recently recommended, but limited data are available regarding long-term use in clinical practice. The objective of the study was to determine the adherence to thienopyridine therapy after stent implantation, factors associated with suboptimal adherence, and association of suboptimal adherence with mortality.. We evaluated 5,263 older patients (>65 years) who received DES and 6,081 older patients who received bare-metal stents (BMS) from December 1, 2003, to March 31, 2006, in Ontario, Canada, who were eligible to receive 12 months of thienopyridine at minimal cost.. Primary nonadherence was observed among 6.9% in the DES group and 7.1% in the BMS group that did not fill a single prescription of thienopyridine within 1 year of stent implantation. Premature discontinuation occurred in a progressive manner, with 28% in the DES group and 34% in the BMS group discontinuing therapy by 6 months. Low-income patients eligible for a waiver of deductible and dispensing fee were almost 70% more likely to fill their first prescription. For DES patients, primary nonadherence (hazard ratio [HR] 2.68, 95% CI 1.77-4.07), 12-months proportional days covered <80% (HR 2.39, 95% CI 1.67-3.43), and prematurely discontinuing therapy within 6 months (HR 2.64, 95% 1.60-4.35) were associated with an increased risk of death.. We found suboptimal patterns of adherence to thienopyridine therapy after DES implantation that was strongly associated with an increased mortality risk. Eliminating any costs for thienopyridine therapy may be an effective strategy to increase medication adherence.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Ontario; Patient Compliance; Prescription Drugs; Prospective Studies; Pyridines; Survival Rate; Time Factors; Treatment Outcome

Topics: Clopidogrel; Coronary Artery Disease; Diabetes Mellitus; Disease Progression; Drug-Eluting Stents; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Ticlopidine; Time Factors; Treatment Outcome

Bleeding among patients with acute myocardial infarction (AMI) is associated with worse long-term outcomes. Although the mechanism underlying this association is unclear, a potential explanation is that withholding antiplatelet therapies long beyond resolution of the bleeding event may contribute to recurrent events.. We examined medication use at discharge, 1, 6, and 12 months after AMI among 2498 patients in the Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) registry. Bleeding was defined as non-coronary artery bypass graft-related Thrombolysis of Myocardial Infarction major/minor bleeding or transfusion among patients with baseline hematocrit > or =28%. Logistic regression was used to evaluate the association between bleeding during the index AMI hospitalization and medication use. In-hospital bleeding occurred in 301 patients (12%) with AMI. Patients with in-hospital bleeding were less likely to be discharged on aspirin or thienopyridine (adjusted odds ratio=0.45; 95% CI, 0.31 to 0.64; and odds ratio=0.62; 95% CI, 0.42 to 0.91, respectively). At 1 month after discharge, although patients with in-hospital bleeding remained significantly less likely to receive aspirin (odds ratio=0.68; 95% CI, 0.50 to 0.92), use of thienopyridines in the 2 groups started to become similar. By 1 year, antiplatelet therapy use was similar among patients with and without bleeding. Postdischarge cardiology follow-up was associated with greater antiplatelet therapy use than either primary care or no clinical follow-up.. Patients whose index AMI is complicated by bleeding are less likely to be treated with antiplatelet therapies during the first 6 months after discharge. Early reassessment of antiplatelet eligibility may represent an opportunity to reduce the long-term risk of adverse outcomes associated with bleeding.

Topics: Acute Disease; Adult; Aged; Aspirin; Female; Follow-Up Studies; Hematocrit; Hemorrhage; Hospitals; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Registries; Regression Analysis

Prolonged periods of dual antiplatelet therapy (DAT), i.e., aspirin plus a thienopyridine, are currently recommended to prevent late drug-eluting stent (DES) thrombosis. The aim of our study was to determine the risk and predictors of bleeding and compliance associated with such prolongation of DAT. In this observational study we examined 2,355 consecutive patients undergoing successful DES implantation at 4 hospitals in Italy from June 2002 to December 2004. Bleeding events occurring on DAT and warfarin or in the first 30 days after stent implantation were excluded. Median duration of DAT was 209 days (interquartile range 178 to 444) and only 158 patients (6.7%) prematurely discontinued DAT. The overall bleeding rate was 1.9% (45), with major bleeding in 19 (0.8%) and minor bleeding in 26 (1.1%). Independent predictors of bleeding were DAT (hazard ratio 19.8, 95% confidence interval [CI] 3.69 to 106.34, p <0.001) and age >65 years (hazard ratio 2.15, 95% CI 1.16 to 4.00, p = 0.02). In patients on DAT, the incidence rate (30 days to 18 months) of any bleeding event was 2.57 per 100 person-years (95% CI 1.85 to 3.48) and major bleeding was 1.10 per 100 person-years (95% CI 0.65 to 1.74). In conclusion, DAT after DES implantation is well tolerated and associated with a very low risk of major bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Confidence Intervals; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Immunosuppressive Agents; Incidence; Italy; Male; Middle Aged; Myocardial Infarction; Patient Compliance; Platelet Aggregation Inhibitors; Prospective Studies; Pyridines; Risk Factors; Sirolimus; Time Factors

Thienopyridine use, in particular clopidogrel in acute coronary syndromes, has been associated with an improvement in outcome. However, little information is available regarding their bleeding risk when used in combination with other antithrombotic agents and revascularisation.. In a large, multinational, prospective registry, the Global Registry of Acute Coronary Events, the major bleeding rate (using GRACE criteria) of 27,358 patients with unstable angina or non-ST-elevation myocardial infarction was recorded during index admission. The interaction of thienopyridines on major bleeding with other antithrombotic agents and with revascularisation was analysed.. The 11,478 patients who received thienopyridines during hospitalisation experienced a significant increase in major bleeding (2.8% with thienopyridines, 2.2% without thienopyridines; p=0.002). No significant interaction with glycoprotein IIb/IIIa inhibitors and thienopyridines was seen with regard to bleeding. Thienopyridines with unfractionated heparin did not alter bleeding risk, but thienopyridines with low molecular weight heparin was associated with a significant excess of bleeding (2.1% with thienopyridines, 1.3% without thienopyridines; p=0.004). There was no significant difference in major bleeding with thienopyridines in patients who did or did not undergo revascularisation.. Major bleeding was increased in patients receiving thienopyridines. No increase in bleeding risk was seen in patients having revascularisation.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Electrocardiography; Female; Hemorrhage; Hospital Mortality; Humans; International Cooperation; Male; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Revascularization; Probability; Prognosis; Prospective Studies; Pyridines; Registries; Risk Assessment; Severity of Illness Index; Survival Analysis; Thromboembolism

Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and healthcare providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction, and death. This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating the patient and healthcare providers about hazards of premature discontinuation. It also recommends postponing elective surgery for 1 year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents.

Topics: Angioplasty, Balloon, Coronary; Aspirin; Coronary Thrombosis; Drug Delivery Systems; Drug Therapy, Combination; Elective Surgical Procedures; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Period; Practice Guidelines as Topic; Pyridines; Stents; Time Factors

Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and healthcare providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction, and death. This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating the patient and healthcare providers about hazards of premature discontinuation. It also recommends postponing elective surgery for 1 year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents.

Topics: Angioplasty, Balloon, Coronary; Aspirin; Coronary Thrombosis; Drug Delivery Systems; Drug Therapy, Combination; Elective Surgical Procedures; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Period; Practice Guidelines as Topic; Pyridines; Stents; Time Factors

and Overview. Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and health care providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction and death.. This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating patients and health care providers about hazards of premature discontinuation. It also recommends postponing elective surgery for one year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents.

Topics: Aspirin; Coronary Disease; Coronary Thrombosis; Drug Administration Schedule; Education, Professional; Elective Surgical Procedures; Humans; Myocardial Infarction; Patient Education as Topic; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Complications; Pyridines; Risk Factors; Stents; Time Factors

Topics: Angina, Unstable; Cardiac Catheterization; Clinical Trials as Topic; Clopidogrel; Coronary Angiography; Data Interpretation, Statistical; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Stents; Syndrome; Ticlopidine; Time Factors

Although drug-eluting stents (DES) significantly reduce restenosis, they require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy after DES placement for acute myocardial infarction (MI) are unknown.. We used prospectively collected data from a 19-center study of MI patients to examine the prevalence and predictors of thienopyridine discontinuation 30 days after DES treatment. We then compared the mortality and cardiac hospitalization rates for the next 11 months between those who stopped and those who continued thienopyridine therapy. Among 500 DES-treated MI patients who were discharged on thienopyridine therapy, 68 (13.6%) stopped therapy within 30 days. Those who stopped were older, less likely to have completed high school or be married, more likely to avoid health care because of cost, and more likely to have had preexisting cardiovascular disease or anemia at presentation. They were also less likely to have received discharge instructions about their medications or a cardiac rehabilitation referral. Patients who stopped thienopyridine therapy by 30 days were more likely to die during the next 11 months (7.5% versus 0.7%, P<0.0001; adjusted hazard ratio=9.0; 95% confidence interval=1.3 to 60.6) and to be rehospitalized (23% versus 14%, P=0.08; adjusted hazard ratio=1.5; 95% confidence interval=0.78 to 3.0).. Almost 1 in 7 MI patients who received a DES were no longer taking thienopyridines by 30 days. Prematurely stopping thienopyridine therapy was strongly associated with subsequent mortality. Strategies to improve the use of thienopyridines are needed to optimize the outcomes of MI patients treated with DES.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cause of Death; Clopidogrel; Combined Modality Therapy; Coronary Restenosis; Drug Administration Schedule; Drug Implants; Female; Follow-Up Studies; Hospitalization; Humans; Life Tables; Male; Middle Aged; Mortality; Myocardial Infarction; Patient Education as Topic; Platelet Aggregation Inhibitors; Prevalence; Proportional Hazards Models; Prospective Studies; Pyridines; Registries; Sirolimus; Stents; Survival Analysis; Thrombosis; Ticlopidine; Treatment Outcome; Treatment Refusal

Few data exist on the use of aggressive combination therapy with thienopyridines and glycoprotein IIb/IIIa inhibitors in higher risk patients with an acute coronary syndrome (ACS). The aim of this study was to characterize the combined use of these agents and the associated hospital outcomes in patients with ACS enrolled in the multinational Global Registry of Acute Coronary Events. Data from 8,081 patients with non-ST-segment elevation myocardial infarction or unstable angina were analyzed. Of these patients, 5,070 (62.7%) received aspirin and a thienopyridine, and the remainder received aspirin, a thienopyridine, and a glycoprotein IIb/IIIa blocker. The presence of a non-ST-segment elevation myocardial infarction; a history of diabetes or coronary artery bypass surgery; performance of in-hospital catheterization, percutaneous coronary intervention, or coronary artery bypass grafting; and in-hospital use of heparin were independent predictors of the use of triple antiplatelet therapy with aspirin, thienopyridines, and glycoprotein IIb/IIIa blockers. Increased diastolic blood pressure and increased serum creatinine were associated with a failure to prescribe triple therapy. An increased risk of major bleeding during hospitalization was associated with the use of triple antiplatelet therapy (odds ratio 1.6, 95% confidence interval 1.2 to 2.2). Aggressive antiplatelet therapy was used in approximately 2 of every 5 patients presenting with an ACS. Triple therapy was associated with the performance of catheterization and/or percutaneous coronary intervention, as well as high-risk patient features. Although no differences in hospital death rates were evident in patients receiving triple therapy, this population was at significantly increased risk of major bleeding episodes during hospitalization.

Topics: Aged; Angina, Unstable; Drug Therapy, Combination; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines

We sought to determine the frequency and timing of complications at our institution when surgery was performed within two months of coronary stent placement.. The optimal delay following coronary stent placement prior to non-cardiac surgery is unknown.. We analyzed the Mayo Clinic Percutaneous Coronary Intervention and Surgical databases between 1990 and 2000 and identified 207 patients who underwent surgery in the two months following successful coronary stent placement.. Eight patients (4.0%) died or suffered a myocardial infarction or stent thrombosis. All 8 patients were among the 168 patients (4.8%, 95% confidence interval [CI] 2.1 to 9.2) undergoing surgery six weeks after stent placement; the frequency of these events ranged from 3.8% to 7.1% per week during each of the six weeks. No events occurred in the 39 patients undergoing surgery seven to nine weeks after stent placement (0%, 95% CI 0.0 to 9.0).. These data suggest that, whenever possible, non-cardiac surgery should be delayed six weeks after stent placement, by which time stents are generally endothelialized, and a course of antiplatelet therapy to prevent stent thrombosis has been completed.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Blood Transfusion; Coronary Angiography; Coronary Disease; Coronary Thrombosis; Female; Humans; Male; Middle Aged; Minnesota; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Pyridines; Retrospective Studies; Stents; Surgical Procedures, Operative; Time Factors; Treatment Outcome; Warfarin

Topics: Angioplasty, Balloon, Coronary; Fibrinolytic Agents; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Recurrence