Evidence of platelet sensitization to ADP following discontinuation of clopidogrel therapy in patients with stable coronary artery disease.

Epidemiological studies have linked clopidogrel discontinuation with an increased incidence of ischemic events. This has led to the hypothesis that clopidogrel discontinuation may result in a pharmacological rebound. We evaluated the impact of clopidogrel discontinuation on platelet function.

Genetic determinants of response to aspirin: appraisal of 4 candidate genes.

Introduction: Intersubject variability in platelet response to aspirin could be related to genetic factors that regulate platelet enzymes or receptors. This study evaluates the impact of the selected polymorphisms in the COX-1 gene, the CYP5A1 gene, the P2RY1 receptor gene, and the GPIIbIIIa receptor gene on platelet response to aspirin and risk of suffering from major adverse cardiovascular and cerebrovascular events (MACCE).

Materials And Methods: 192 Caucasian patients with stable coronary artery disease treated with daily aspirin were recruited and followed for 3 years.

Comparison of electrocardiographic recordings in open-chest and closed-chest swine models.

The aim of our study was to compare the electrocardiographic recordings in an experimental open-chest swine model before and after left-sided thoracotomy to detect any surgery-induced fluctuations that might interfere with subsequent experimental interventions. We obtained electrocardiograms from 8 deeply anesthetized domestic swine and compared the respective ST-segment potentials obtained after vascular surgery and after left-sided thoracotomy and dissection of the left anterior descending coronary artery. Compared with baseline recordings, no significant ST-segment deviation on any of the electrocardiographic leads occurred after vascular surgery.

Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease.

Background: Platelets, long believed to be incapable of de novo protein synthesis, may retain their ability to form the cyclooxygenase (COX) enzyme once it has been inactivated by aspirin. This may explain the inefficacy of the drug to induce sustained platelet inhibition in certain patients. We evaluated the stability of platelet inhibition following once-daily enteric-coated aspirin administration.

Prevalence of unresponsiveness to aspirin and/or clopidogrel in patients with stable coronary heart disease.

This study sought to assess whether inadequate platelet responses to aspirin and clopidogrel are distinct phenomena caused by different mechanisms or different facets of the same phenomenon (i.e., general platelet hyperactivity).

Week-long high-maintenance dose clopidogrel regimen achieves better platelet aggregation inhibition than a standard loading dose before percutaneous coronary intervention: results of a double-blind, randomized clinical trial.

Background: Adequate platelet inhibition before percutaneous coronary intervention (PCI) reduces periprocedural and long-term ischemic complications. Reduced response to clopidogrel has been associated with subsequent major adverse cardiovascular events. Strategies to optimize platelet inhibition pre-PCI are under investigation.

Response to aspirin in healthy individuals. Cross-comparison of light transmission aggregometry, VerifyNow system, platelet count drop, thromboelastography (TEG) and urinary 11-dehydrothromboxane B(2).

Variable biological effect of aspirin is suggested to be related to pharmacological resistance. The incidence of this so-called "resistant" state varies with the study population and the assay used. We determined performance features of five assays used to assess aspirin effects in non-smoking healthy volunteers not taking any drug known to interfere with platelet function.

Possibility of a rebound phenomenon following antiplatelet therapy withdrawal: a look at the clinical and pharmacological evidence.

The importance of regular administration of antiplatelet drugs in patients suffering from coronary artery disease stands on firm grounds, as large meta-analyses have shown these therapies to drastically reduce the risk of death. Although the current guidelines published jointly by the American Heart Association, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, the American College of Surgeons and the American Dental Association stress the hazards of premature discontinuation of antiplatelet drugs, abrupt withdrawal remains widespread, with potentially catastrophic consequences. In the limited state of knowledge on antiplatelet drug withdrawal, an early sound of alarm has risen from early thromboembolic complications reported after the interruption of treatment in patients who require antiplatelet therapy for prevention of ischemic vascular disease.

Insights into the interpretation of light transmission aggregometry for evaluation of platelet aggregation inhibition by clopidogrel.

Introduction: When studying the efficacy of clopidogrel to inhibit platelet aggregation by light transmission aggregometry, technical decisions must be taken prior to assessment or during analysis, including, but not limited to, concentration of agonist to use and timing of the evaluation of the response on the aggregation curve obtained (peak ADP-stimulated platelet aggregation vs. late aggregation). We investigated how some of these technical modalities affected the results of platelet aggregation obtained after clopidogrel administration.

Evaluation of the platelet count drop method for assessment of platelet function in comparison with "gold standard" light transmission aggregometry.

Introduction: Hyporesponsiveness to antiplatelet agents has been linked to an increased risk of major adverse cardiovascular events. However, light transmission aggregometry (LTA), the gold standard methodology for assessing platelet function, requires expertise and is labour-intensive, which render its use in clinical settings impractical. We assessed whether platelet count drop (PCD), a technique widely available in any haematology laboratory, could replace LTA in testing for inhibition of platelet aggregation induced by antiplatelet agents.

Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin.

Background: Several patient characteristics have been shown to increase the risk of inadequate platelet inhibition by aspirin, yet underlying mechanisms remain mostly unknown. We explored whether oxidative stress, via isoprostane formation, was associated with inadequate platelet response to aspirin. Additionally, we sought to investigate whether individual pre-selected demographic, hematological or biochemical parameters further increased the risk of inadequate platelet response to aspirin.

Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients.

Aims: We investigated the comparability of platelet function tests in quantifying platelet inhibition achieved by clopidogrel.

Methods And Results: This pre-specified substudy of a randomized, double-blind trial included 116 patients with stable coronary artery disease requiring diagnostic angiography. Patients received clopidogrel for 1 (300 or 600 mg) or 7 days (300 + 75 or 150 mg daily) before the procedure.

Assessment of VerifyNow P2Y12 assay accuracy in evaluating clopidogrel-induced platelet inhibition.

The emergence of point-of-care assays enabling bedside testing such as the VerifyNow P2Y12 system might prove useful in clinical settings. The aim of this study was to evaluate the ability of the VerifyNow P2Y12 assay to estimate the inhibition of platelet aggregation provided by clopidogrel in the absence of baseline off-drug aggregation data. Sixty-eight patients with coronary artery disease scheduled to initiate clopidogrel therapy underwent platelet aggregation testing by VerifyNow P2Y12 at baseline and after clopidogrel administration.

A national survey of antimicrobial prophylaxis in adult cardiac surgery across Canada.

Objective: To characterize national and regional patterns of antimicrobial prophylaxis in adult cardiac surgery across Canada.

Design: Retrospective, cross-sectional analysis.

Setting: Thirty-three adult cardiac surgical centres across Canada.

A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease.

Aims: We sought to compare the results obtained from six major platelet function tests in the assessment of the prevalence of aspirin resistance in patients with stable coronary artery disease.

Methods And Results: 201 patients with stable coronary artery disease receiving daily aspirin therapy (> or =80 mg) were recruited. Platelet aggregation was measured by: (i) light transmission aggregometry (LTA) after stimulation with 1.

Aspirin resistance: truth or dare.

Acetylsalicylic acid, or aspirin (ASA), is widely used in patients with cardiovascular disease to prevent acute ischemic events. However, platelet response to ASA is not equal in all individuals, and a high variability in the prevalence of ASA resistance is reported in the literature (0.4-83%).

Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates.

ST-segment depression is commonly seen in patients with acute coronary syndromes. Most authors have attributed it to transient reductions in coronary blood flow due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and dynamic focal vasospasm at the site of coronary artery stenosis. However, ST-segment depression was never reproduced in classic animal models of coronary stenosis without the presence of tachycardia.

Absence of clinically significant increase in pulmonary artery pressure after intravenous perflutren injection for myocardial perfusion imaging in pigs.

Objective: We sought to evaluate the impact of a continuous intravenous infusion of perflutren on systemic pulmonary artery pressures at clinically relevant doses for myocardial perfusion imaging in pigs.

Methods: Five anesthetized, ventilated, open-chest pigs were administered perflutren intravenously at a rate of 0.0364 mL/kg/min over approximately 5 minutes.

Resistance to clopidogrel: a review of the evidence.

Current available data show that about 4% to 30% of patients treated with conventional doses of clopidogrel do not display adequate antiplatelet response. Clopidogrel resistance is a widely used term that remains to be clearly defined. So far, it has been used to reflect failure of clopidogrel to achieve its antiaggregatory effect.

Analysis of bleeding complications associated with glycoprotein IIb/IIIa receptors blockade in patients with high-risk acute coronary syndromes: insights from the PRISM-PLUS study.

We aim to characterize the hemorrhagic complications and predictors of increased bleeding risk in a population of patients with high-risk acute coronary syndromes (ACS), enrolled in the PRISM-PLUS study. Patients treated with heparin plus tirofiban had more bleeding events compared to patients treated with heparin alone. No significant increase in major bleeding, thrombocytopenia, blood loss and blood products transfusions was observed among the patients who received the combination therapy.

A critical appraisal of the CURE trial: role of clopidogrel in non-ST-segment elevation acute coronary syndromes.

Background: A clinical study, the CURE trial, compared the use of clopidogrel/acetylsalicylic acid (ASA) to ASA alone in 12,562 patients with non-ST-segment elevation acute coronary syndromes (ACS). Results of the trial suggested a possible first-line role for the more expensive combination of clopidogrel/ASA.

Objective: To perform a critical appraisal of the CURE trial, to determine the efficacy and safety of the clopidogrel/ASA combination in the management of ACS patients and to describe the population most likely to benefit from this combination.

Inhibition of streptokinase-induced, antibody-mediated platelet aggregation with tirofiban after exposure to streptokinase or streptococcal infection.

Study Objective: To evaluate the effect of tirofiban (a glycoprotein IIb-IIIa inhibitor) in preventing streptokinase-induced, antibody-mediated platelet aggregation after administration of streptokinase or development of a streptococcal infection.

Design: Prospective analysis.

Setting: Research center of a Canadian hospital.