Adjunctive Antiplatelet Treatment in Primary Percutaneous Coronary Intervention

Background: Despite significant advances in the management of coronary heart disease, myocardial infarction is still associated with high mortality. Thienopyridines and glycoprotein IIb/IIIa inhibitors have been used extensively in the management of ST segment elevation myocardial infarction. Objective: This article discusses the evidence from clinical trials and registries concerning the benefits of thienopyridines, reviews the results of published multicenter, randomized controlled trials of the efficacy and safety of platelet GPIIb/IIIa inhibitors in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) and presents the recent guidelines.Methods: Data for this review were identified by broad searches of MEDLINE, Current Contents and references from relevant articles (1980-2011); numerous articles were identified through searches of the extensive files of the authors and selected based on their importance, oppurtunity for further reading and up to date information. Search terms included thienopyridines, platelet aggregation inhibitors, percutaneous coronary intervention, antiplatelet therapy, ST elevation myocardial infarction (STEMI), primary percutaneous coronary intervention. Only English language papers were reviewed. No restrictions were set on the type of papers.Results: Clopidogrel is the most commonly used thienopyridine in patients undergoing primary PCI. Recently new inhibitors of P2Y12 receptors, like prasugrel and ticagrelor, have become available, which have a more potent and rapid onset of action, with similar safety profile, which is specifically targeted to the subgroup of primary PCI. On the other hand, the platelet glycoprotein IIb/IIIa inhibitors have aided and abetted medical management of acute coronary syndromes and proved an important adjunctive therapy in percutaneous coronary interventions. Platelet glycoprotein IIb/IIIa inhibitors, although not recommended for routine therapy, have an important role at the time of primary PCI, particularly in high-risk subgroups, like the diabetics and those with a heavy thrombotic burden.Conclusion: Clopidogrel remains the most used thienopyridine together with aspirin in patients undergoing primary PCI but there are currently available new inhibitors of P2Y12 receptors, like prasugrel and ticagrelor, which have a more potent and rapid onset of action, with similar safety profile. Glycoprotein IIb/IIIa antagonists, although not recommended for routine therapy, can be of use at the time of primary PCI, particularly in high-risk subgroups

Sepsis favors high-on-clopidogrel platelet reactivity

<p>High-on-treatment platelet reactivity (HPR) is associated with ischemic events in patients on antiplatelet therapy with a history of cardiovascular disease. On the other hand, recent data have associated sepsis with adverse cardiovascular events in patients admitted with bacteremia or respiratory infection. We aimed to assess P2Y₁₂-mediated platelet reactivity (PR) during sepsis and recovery in patients under clopidogrel. This was a prospective observational study. Incoming patients presenting with signs/symptoms of sepsis already on a maintenance dose of clopidogrel of 75 mg qd for cardiovascular events were included in this study. Patients were assessed for their PR on presentation and following septic syndrome, using the VerifyNow point-of-care P2Y₁₂ assay. Patients were excluded in the presence of evidence of noncompliance to antiplatelet regimen or in need of discontinuation during this study. Twenty-two septic patients on clopidogrel were included in this study (Supplemental Figure S1). Clopidogrel was administered for previous stroke, coronary, and peripheral artery disease in 27.3, 40.9, and 31.8% of patients, respectively. The main site of infection was respiratory tract followed by urinary tract, while the same amounts of gram-negative and -positive pathogens were isolated. HPR was noted in 77% and 29% of patients during sepsis and recovery, respectively, presenting a significant decrease in P2Y₁₂ reaction units values during follow-up [240.7 ± 58.3 versus 179.5 ± 58.4, 95% CI (–102.7, –39.76), <i>p</i> = 0.0002]. Five patients died of infection, while no adverse cardiovascular events were noted in our study. Our study shows that sepsis may favor HPR, which is reversed when recovery occurs. This finding may underlie the adverse cardiovascular events in patients admitted with sepsis, possibly requiring alteration of antiplatelet regimen during the inflammation period.</p

Dyspnea in patients treated with P2Y12 receptor antagonists: insights from the GReek AntiPlatElet (GRAPE) registry

In ‘real life’ acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87–3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y12 receptor antagonist, dyspnea occurs commonly, particularly when ticagrelor is administered. Non-persistence with antiplatelet agents at discharge is more frequently observed among dyspnea-reporters

Mechanisms of Atrial Fibrillation: How Our Knowledge Affects Clinical Practice

Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm that onfirm the most common triggers due to their distinct anatomical and electrophysiological properties. As a result, their electrical isolation by ablation is the cornerstone of invasive AF treatment. Multiple factors and comorbidities affect the atrial tissue and lead to myocardial stretch. Several neurohormonal and structural changes occur, leading to inflammation and oxidative stress and, consequently, a fibrotic substrate created by myofibroblasts, which encourages AF perpetuation. Several mechanisms are implemented into daily clinical practice in both interventions in and the medical treatment of atrial fibrillation