Use Of Antiplatelet Therapies Research Articles

Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients

BackgroundAging is a complex physiological phenomenon, intricately associated with cardiovascular pathologies, where platelets play a central pathophysiological role. Although antiplatelets are commonly employed to prevent and treat major adverse cardiovascular events, aging associated intraplatelet changes remain largely unexplored. MethodsPlatelets were studied in high cardiovascular risk patients (aged 40–100 years) comparing them to younger healthy subjects. This was followed by cross sectional and longitudinal mice studies. Flow cytometry, biochemical and molecular assays were used to study platelets comprehensively. FindingsCVD Patients were categorized in the age groups 40–59, 60–79, and 80–100 years. Progressive decline in platelet health was observed in the 40–79 years age cohort, marked by increase in oxidative stress, hyperactivation and apoptotic markers. Paradoxically, this was reversed in patients aged above 79 years and the improved platelet phenotype was associated with lower oxidative damage. The platelets from the very old (80–100 year) group were found to be preloaded with increased antioxidants, which also contributed to higher resistance against induced redox insults. Cross sectional mouse studies excluded the effect of comorbidities and medications. Longitudinal mouse studies implicate an adaptive increase in antioxidant levels as the mechanism. InterpretationWe report a novel age associated, non-linear redox regulation in platelets in both humans and mice. In advanced age, there occurs an adaptive increase in platelet antioxidants, reducing the intracellular ROS and leading to a healthier platelet phenotype. Clinically, our results advocate the use of less aggressive antiplatelet therapies for CVD in the elderly population. FundStudy funded by NIH-NHLBI, RO1-HL122815 and RO1-HL115247.

Increased Transfusion Requirements with Pharmacologic Thromboembolism Prophylaxis During Inflammatory Bowel Disease Exacerbation.

Inflammatory bowel disease (IBD) exacerbation requiring hospitalization increases the risk of venous thromboembolism (VTE), and current guidelines recommend pharmacologic VTE prophylaxis (PVTEP). Bleeding risks with PVTEP in this population are poorly defined, and no study has investigated packed red blood cell (PRBC) transfusion requirements in this population. We conducted a chart review of all adult hospitalizations for IBD exacerbation within the Northwell Healthcare system. Patient characteristics recorded included demographics, disease type ulcerative colitis or Crohn's disease, severe disease defined by inpatient corticosteroid or biologic use, and admission hemoglobin. Inpatient use of PVTEP and anti-platelet therapies were identified. The primary outcome was the occurrence of any packed red blood cell (PRBC) transfusion. In total, 717 patients met inclusion criteria, accounting for 891 admissions. PVTEP was used during 60.4% of admissions, and 11.1% of patient admissions included a transfusion event. Severe disease patients receiving PVTEP had an 18.6% transfusion risk, versus 11.1% for those not receiving PVTEP, OR 1.82, CI (1.04-3.17). One multivariable analysis transfusion was associated with PVTEP, OR 2.11, 95% CI 1.18, 3.77, p = 0.0120, disease severity OR 3.17, 95% CI 1.81,5.54, p < 0.0001, anti-platelet therapies OR 2.46, 95% CI 1.23-4.90, p = 0.0107, bowel resection OR 3.88, 95% CI 1.97,7.63, p < 0.0001 and decreased admission hemoglobin OR 2.01, 95% CI 1.73-2.32, p < 0.0001, but not disease type ulcerative colitis OR 0.71, 95% CI 0.42-1.20. PVTEP during IBD exacerbation is associated with increased PRBC transfusions. Our findings do not constitute a contraindication to PVTEP, but may be incorporated into patient counseling during inpatient IBD management.

Role of oral anticoagulant therapy for secondary prevention in patients with stable atherothrombotic disease manifestations.

Coronary artery disease and peripheral arterial disease are strong predictors of risk for a future ischemic event. Despite the utilization of effective secondary prevention strategies, the prevalence of ischemic recurrences remains high, underscoring the need for effective secondary prevention antithrombotic treatment regimens. To date, most of the tested approaches have been with the use of antiplatelet therapies, used either individually or in combination. However, most recent findings support the potential role of oral anticoagulant therapy in addition to antiplatelet therapy to reduce the risk of ischemic recurrences. This approach has been tested in both acute and stable settings of patients with cardiovascular disease manifestations. The present manuscript provides an overview on the rationale and clinical trial updates on the role of oral anticoagulant therapy, in particular rivaroxaban used at the so-called vascular protection dose, in adjunct to antiplatelet therapy (i.e. aspirin), a strategy known as dual pathway inhibition, for secondary prevention of ischemic recurrences in patients with stable atherosclerotic disease manifestations.

Antithrombotic Therapy in Patients with Malignant Lymphoproliferative Disorders Treated with Ibrutinib

Background. Antithrombotic therapy in chronic lymphocytic leukemia (CLL) patients is challenging, as this category of patients is initially characterized by high risk of hemorrhagic complications. The use of ibrutinib influencing the platelet function constitutes an additional bleeding risk. A crucial task consists in risk minimization of both hemorrhagic complications and thrombosis while sticking to ibru-tinib treatment. Aim. To assess the feasibility of antithrombotic therapy in CLL patients receiving ibrutinib and having indications for this therapy, as well as the use of dual antiplatelet and dual antithrombotic therapies. Materials &amp; Methods. The trial included patients with CLL (n = 190), mantle cell lymphoma (n = 5), and Waldenstrom macroglobulinemia (п = 2) aged 32 to 91 years (median 66 years). The number of female patients was 70, aged 39 to 83 years (median 64 years) and the number of male patients was 127, aged 32 to 91 years (median 66 years). The patients were at different stages of ibrutinib treatment within 5 to 56 months. In this work methods of nonparametric statistics were used. All data are shown in the form of median and interquartile range or absolute numbers and percentages. Results. Antithrombotic therapy during ibrutinib administration was used in 29 (14,7 %) patients. The new oral anticoagulants (NOAC) had to be prescribed to 26 patients with atrial fibrillation (AF). Dual antiplatelet therapy was used in 3 patients who underwent percutaneous coronary intervention with subsequent revascularization. In 2 patients with AF who underwent coronary stenting the dual antithrombotic therapy instead of the triple one was administered according to the management algorithm for patients with high risk of hemorrhagic complications. In 6 patients out of those who had AF and received NOAC the drug was withdrawn because of thrombocytopenia. Hemorrhagic manifestations which were the reason of NOAC withdrawal were observed in 1 female patient in the form of gross hematuria recurring when anticoagulant treatment was switched to the minimal effective doses and also when the administered anticoagulant was replaced with another one used in the minimal dose effective for stroke prevention in patients with AF. Hemorrhagic manifestations which were the reason of anticoagulant dose reduction emerged in 4 patients, and 3 patients required another anticoagulant for the same reason. In 5 patients there was no need to change the anticoagulant treatment. In 10 NOAC recipients no hemorrhagic syndrome was observed. None of 5 patients receiving dual antithrombotic therapy showed hemorrhagic complications within 3 to 14 months. The incidence of them in women is more than twice as high as in men. Conclusion. Hemorrhagic manifestations in patients receiving ibrutinib and antithrombotic therapy were not life threatening and, in most cases, did not require drug withdrawal. Thrombocytopenia was the main reason for NOAC withdrawal. A thorough follow-up of patients receiving ibrutinib and antithrombotic therapy allows for timely correction of it if necessary. It involves dose reduction, anticoagulant replacement, and in rare cases the withdrawal of antithrombotic therapy with subsequent consideration of the feasibility of its resumption. As a rule, the need for different variants of antithrombotic therapy is not an obstacle to either assignment or continuation of antineoplastic treatment with ibrutinib.

A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology Guideline.

The previous BSH guideline for the management of erythrocytosis was published in 2005 (McMullin et al, 2005) and amended in 2007 (McMullin et al, 2007). Here, we re‐evaluate the literature formulate guidance on the management of specific situations encountered in polycythaemia vera (PV) and the management of the other types of secondary erythrocytosis. Recommendations for the diagnostic pathway of investigation of an erythrocytosis, risk stratification and management of PV are in the accompanying guideline (McMullin et al, 2018). We review evidence and outline guidance on management of acute thrombotic events and secondary prevention of thrombosis in PV. The unusual thrombotic events, splanchnic vein and cerebral vein thromboses are discussed and haemorrhage. The specific situations of surgery and pregnancy and guidance on management of pruritus are included. The evidence for the management of other causes of erythrocytosis, including idiopathic erythrocytosis, congenital erythrocytosis, hypoxic pulmonary disease and post‐transplant erythrocytosis, is reviewed and recommendations made.

Anticoagulation in Atherosclerotic Disease.

The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y12-receptor antagonists, some patients with artery disease continue to experience recurrent cardiovascular ischaemic events due to excessive thrombin generation beyond the acute period. As a result, studies have tested non-vitamin K antagonist oral anticoagulants (NOACs), specifically the factor Xa inhibitors, either alone or in combination with antiplatelet therapy, in the management of arterial disease. For the first time, the COMPASS study investigated low-dose anticoagulation in stable coronary heart disease or peripheral arterial disease. The addition of 2 × 2.5 mg rivaroxaban to long-term aspirin therapy not only prevented cardiovascular death, myocardial infarction and stroke, but even reduced all-cause mortality by a relative 18% after a mean follow-up of 23 months. This benefit came at the expense of more gastrointestinal bleeding, which might be reduced by the addition of a proton pump inhibitor (investigations are ongoing). Interestingly, however, there was no increase in fatal or intracranial haemorrhages. Therefore, a new standard therapy for high-risk patients with atherosclerotic disease may become available in the near future.

Abstract 131: Impact of Concomitant Use of Antiplatelet and Anticoagulation Therapies on Outcomes in Patients With Intracerebral Hemorrhage

Background: The impact of the preceding use of concomitant use of antiplatelet and anticoagulation therapies on outcomes of intracerebral hemorrhage (ICH) has not been thoroughly investigated. Methods: We analyzed 138,834 patients presenting with ICH between October 2013 and December 2016 from 1661 hospitals participating in the Get With The Guidelines-Stroke program. Multivariable logistic regression was used to evaluate the impact of concomitant antiplatelet therapy on in-hospital mortality in anticoagulation-related ICH. Results: Of 138,834 patients (mean [SD] age 68.4 [15.3] years; 48.0% women), 118,219 (85.2%) patients were not receiving any oral anticoagulant (OAC), 15,777 (11.4%) were receiving warfarin and 4,838 (3.5%) were receiving non-vitamin K oral anticoagulants (NOACs) prior to ICH. Stroke severity as measured by NIHSS was similar across three groups. Patients receiving warfarin or NOACs were more likely to have single antiplatelet therapy (SAPT) than those receiving no OAC (33.0% for warfarin, 30.7% for NOACs, and 27.3% for no OAC), whereas patients receiving no OAC were more likely to have dual antiplatelet therapy (DAPT) (2.5% for warfarin, 2.3% for NOACs, and 4.4% for no OAC). After adjustment for confounders, SAPT was associated with a slightly higher rate of mortality (33.8% vs. 32.1%, adjusted odds ratio [AOR] = 1.20, 95% CI [1.11-1.30]) than no antiplatelet in patients receiving warfarin, whereas there were no statistically significant differences between SAPT vs. no antiplatelet in patients with no OAC (22.4% vs. 22.9%, AOR = 0.99 [0.95-1.03]) or NOACs (26.8% vs. 26.9%, AOR = 1.09 [0.94-1.26]). DAPT was associated with increased risk of death in patients taking warfarin (46.5% vs. 32.1%, AOR = 2.08 [95% CI, 1.68-2.57]) and no OAC (30.4% vs. 22.9%, AOR = 1.51 [95% CI, 1.40-1.63]). By contrast, in patients taking NOACs, the association of DAPT was not significant but the confidence intervals were wider (32.7% vs. 26.9%, AOR = 1.37 [95% CI, 0.90-2.08]) likely due to small sample size. Conclusions: In patients experienced an ICH, prior concomitant use of antiplatelet therapy (either SAPT or DAPT) significantly increased odds of mortality in patients taking warfarin, but such a difference was not apparent in NOAC-treated ICH patients.

Abstract 21004: Relation Between Optimal Medical Therapy Trends on Outcomes in Patients With Peripheral Arterial Disease and Coronary Artery Disease Undergoing Cardiac Catheterization

Introduction: Peripheral arterial disease (PAD) is a strong predictor of systemic atherosclerosis with substantial morbidity and mortality. Medical management in PAD and coronary artery disease (CAD) has changed in recent eras with the use of high intensity statin and dual antiplatelet therapies. Hypothesis: Test whether mortality and major adverse cardiovascular events (MACE) (death and MI) has decreased over eras among PAD patients undergoning revascularization with percutaneous coronary intervention (PCI). Methods: Longitudinal cohort study of 549 patients who underwent PCI and non-invasive lower arterial study between 1997 and 2008 as identified in the Mayo Clinic PCI registry were stratified into 2 time eras: 1997-2003 (era1), and 2004-2008 (era2). PAD was assessed using the highest resting ABI and stratified according to established categories; &lt; 0.90 (definite PAD); 1.00-1.39 (normal); and ≥ 1.40 defined a non-compressible artery. Kaplan-Meier methods were used to analyze follow-up survival. Results: Stratified by ABI over both time eras, 225 patients had PAD, 94 were non-compressible, and 142 were normal. Overall mortality rates were higher in era2 non-compressible and PAD patients than in non-PAD patients when compared to era1 (58%, 33%, 26%, vs 49% 32%, 19%, p&lt;0.001 for all within-era comparisons) (Figure 1). MACE-free survival were higher in era2 non-compressible and PAD patients than in non-PAD patients when compared to the era1 (64%, 41%, 29% vs 59% 39%, 25%, p≤0.005 for all within-era comparisons). There were significant differences in medical therapy between era2 vs. era1 with higher discharge use of aspirin (98%; 94%), beta-blockers (88%; 66%), any lipid lowering drugs (86%; 76%), ACE inhibitors (67%; 56%), and diuretics (52%; 40%). Conclusions: Over the past two eras, the overall mortality has increased among patients with PAD and non-compressible vessels in era2 vs. era1 despite higher utilization of statin and antiplatelet therapies.

A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative.

Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to support use of these therapies after peripheral artery disease revascularization exist, and much of the rationale for the use of antiplatelet agents after endovascular peripheral revascularization is extrapolated from percutaneous coronary intervention literature. Consequently, guideline recommendations for antithrombotic therapy after lower limb revascularization are inconsistent and not always evidence-based. In this context, the purpose of this structured review is to assess the available randomized data for antithrombotic therapy after peripheral arterial revascularization, with a focus on clinical trial design issues that may affect interpretation of study results, and highlight areas that require further investigation.

Use of over-the-scope clips (OTSC) for hemostasis in gastrointestinal bleeding in patients under antithrombotic therapy.

Background and study aims In patients taking different regimens of antithrombotic and/or anticoagulant therapy, endoscopic management of gastrointestinal bleeding represents a major challenge due to failing endogenous hemostasis. In this retrospective study we report on success rates with the over-the-scope clip (OTSC) system in upper and lower gastrointestinal bleeding in this high-risk patient population. Patients and methods Between February 2011 and June 2014, 75 patients were treated with an OTSC for active gastrointestinal bleeding. Success rates with the first endoscopic therapy, rebleeding episodes, their management and the influence of antithrombotic or anticoagulant therapy were analyzed retrospectively. Results Application of the OTSC resulted in immediate hemostasis (primary success rate) in all 75 patients. However, in 34.7 % a rebleeding episode was noted that could be treated by further endoscopic interventions. Only 3 patients had to be sent to the operating room because of failure of endoscopic therapy. In the rebleeding group the use of antiplatelet therapies was higher (73.1 % vs. 48.9 %). Conclusions Application of the OTSC in GI bleeding results in a high rate of primary hemostasis. Rebleeding occurs in up to 35 % of patients receiving antithrombotic/anticoagulant therapy but can be managed successfully with further endoscopic treatments. Patients in the rebleeding group were more frequently treated with antiplatelet agents. Radiological or surgical therapy was reserved for a small subgroup not successfully managed by repeated endoscopic therapies. OTSC application is the treatment of choice in high-risk patients when conventional clips used as first-line treatment fail.

Adjuvant Antithrombotic Therapy in TAVR

Transcatheter aortic valve replacement (TAVR) has developed into an important alternative to surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis (AS). Adjuvant antithrombotic therapies are commonly used during and after TAVR to decrease the risk of valve thrombosis and thromboembolic cerebrovascular events (CVEs) but consequently increase the risk of bleeding. This article reviews the past and current clinical data regarding adjuvant antithrombotic therapies in TAVR. Cerebrovascular and bleeding events during and after TAVR are associated with substantial morbidity and mortality. Bivalirudin, a direct thrombin inhibitor, has been shown to be safe alternative to unfractionated heparin (UFH) as procedural anticoagulation during TAVR; however, sparse evidence exists to guide use of antiplatelet and anticoagulant therapies in patients after TAVR. Multiple studies comparing different antithrombotic regimens in the post-TAVR setting are currently underway. Current guidelines recommend intra-procedural anticoagulation with UFH for during TAVR and with dual antiplatelet therapy (DAPT) after TAVR. There is a need to better understand the role of adjuvant antithrombotic therapies in TAVR. The results of ongoing studies are needed to develop evidence-based guidance for the use of adjuvant antithrombotic therapies after TAVR.

Oral antiplatelet agents for the management of acute coronary syndromes: A review for nurses and allied healthcare professionals.

We review the use of oral antiplatelet (OAP) therapies in acute coronary syndrome (ACS) management for nurse practitioners (NPs), focusing on current guideline recommendations. Treatment guidelines and clinical articles from PubMed. Guidelines recommend that dual antiplatelet therapy with a P2Y12 inhibitor and aspirin be initiated for ACS management. The P2Y12 inhibitor clopidogrel has established efficacy, but is associated with suboptimal and delayed platelet inhibition and variability in response. The newer P2Y12 inhibitors prasugrel and ticagrelor have demonstrated superior efficacy outcomes versus clopidogrel. Consequently, non-ST-segment elevation ACS (NSTE-ACS) guidelines now recommend that ticagrelor be used in preference to clopidogrel for patients treated with stents or managed medically. Because of their higher potency, prasugrel and ticagrelor are associated with increased bleeding rates versus clopidogrel, but with no increased risk of severe or life-threatening bleeding. Guidelines recommend dual antiplatelet therapy be continued ≥12 months in both medically managed and stented ACS patients, and in some cases beyond this, in absence of high bleeding risk. Updated guidelines assign preference to ticagrelor over clopidogrel for maintenance therapy in patients with NSTE-ACS and ST-elevation myocardial infarction. Enhanced NP understanding of OAP agents and current guidelines could contribute to improved ACS patient management.

JAK2V617F-Positive Patients with Essential Thrombocythemia or Early Primary Myelofibrosis: The Impact of Histological Diagnosis on Outcome

IntroductionIt is acknowledged that an accurate histological diagnosis may distinguish Essential Thrombocythemia (ET) from early Primary Myelofibrosis (early-PMF), which is projected to worse outcome in terms of survival and disease evolution into acute leukemia (AL) or overt myelofibrosis (MF). It is also accepted that the outcome of ET is related to the mutational status, with JAK2V617F mutation having a negative impact. In previous analyses, outcome data derived from the admixture of the two variables, histology and mutational status. Here, we present a large cohort of ET/early-PMF patients positive for the JAK2V617F mutation, with the aim to evaluate the impact on outcome of the sole histological definition.MethodsA clinic-pathologic database of ET patients followed in four Italian Hematology Centers was created and a total of 475 WHO-diagnosed ET or early-PMF JAK2V617F-positive patients was collected. Bone marrow specimens were performed or reviewed at local institution. Baseline clinical/molecular characteristics and outcome measures (vascular complications, disease transformation/progression, overall and event-free survival) were evaluated. In all patients, JAK2V617F allele-burden was assessed in granulocyte DNA by using ipsogen JAK2 MutaQuant Kit (qPCR). The study was approved by the Ethic Committee of each participating Centers.ResultsOverall, 329 WHO-defined ET and 146 early-PMF patients positive for the JAK2V617F mutation were included in the study. Median follow-up was 6.6 years (range: 0.5-32.4). Compared to ET patients, early-PMF patients presented with older age (median, 57 versus 53.5yr, p=0.02), lower hemoglobin levels (median, 14.2 versus 14.5 g/dl, p=0.01), higher leukocyte count (median, 10.4 versus 9.5x109/l, p=0.01), and higher incidence of spleen enlargement (35.9% versus 13.9%, p<0.001). JAK2V617F mutation was heterozygous in 90% and 87% of ET and early-PMF patients, respectively (p=0.34). Use of antiplatelet and cytoreductive therapies was also comparable in the two groups. During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients experienced a total of 59 thrombotic events (arterial: 49%), with an incidence rate of 1,3% patients/yr. The cumulative incidence of thrombosis was 8% and 14% at 5 and 10 years, respectively. Overall, 27 patients (5,6%) and 6 (1.2%) patients evolved to MF and AL, respectively. The cumulative incidence of disease progression into MF/AL was 2% and 5% at 5 and 10 years, respectively. At last contact, 28 (5.8%) patients had died, at a median age of 77.5 years (20-88), for an overall survival of 93.8% at 10 years. In early-PMF compared to ET, the 10-year survival rates (91.6% and 95%, respectively, p=0.75), leukemic transformation rates (6% and 1.2%, respectively, p=0.45) and rates of thrombosis (6.7% and 2.2%, p=0.12) were comparable. However, progression to overt MF at 5 years (4.4% and 0.9%, respectively) and 10 years (11.5% and 1.5%) was significantly worse (p=0.004). Multivariable analysis confirmed this finding and also identified homozygosity for the JAK2V617F mutation (p=0.008) as additional risk factor for disease evolution into secondary MF.The rate of composite outcomes (thrombosis, evolution into overt MF or AL and death) was significantly higher in early-PMF (3.1% vs 2,3% pts/yr) with a combined event-free survival of 69% versus 82% in ET patients at 10 yrs (figure 1).Conclusions. This study eliminates the confounding factor of different molecular status on outcome by focusing on a large cohort of WHO-defined ET/early-PMF patients, all carrying the JAK2V617F mutation. Overall, the study validates the clinical relevance of strict adherence to WHO criteria on prognosis, and particularly on disease progression into secondary MF. [Display omitted] DisclosuresPalumbo:Novartis: Honoraria, Other: Advisory Board. Martinelli:MSD: Consultancy; BMS: Speakers Bureau; Roche: Consultancy; ARIAD: Consultancy; Novartis: Speakers Bureau; Pfizer: Consultancy.

Current antiplatelet agents: place in therapy and role of genetic testing.

Antiplatelet therapies play a central role in reducing the risk of cardiovascular events such as myocardial infarction and stroke. While aspirin, a cyclo-oxygenase-1 inhibitor has been the cornerstone of antithrombotic treatment for several decades, P2Y12 receptor inhibitors cangrelor, clopidogrel, prasugrel, and ticagrelor and protease-activated receptor-1 antagonist vorapaxar, have emerged as additional therapies to reduce the risk of recurrent cardiovascular events in high-risk patients. Recent clinical trials evaluating the role of these agents and major society guideline updates for use of antiplatelet therapies for secondary prevention of cardiovascular events will be examined. The latest studies regarding the appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention will be presented. The current state of genetic and platelet function testing will be reviewed.

Gastrointestinal bleeding in cardiac patients: epidemiology and evolving clinical paradigms.

Cardiac patients are a fast emerging population vulnerable to gastrointestinal bleeding (GIB) due to their use of antithrombotic medications. This review will quantify the GIB risk of cardiac patients prescribed antithrombotic medications, summarize risk-management strategies and highlight knowledge gaps. As the American population ages, it is anticipated that there will be an increased incidence of upper and lower GIB related to age-specific disease, higher burden of comorbidity and increased use of anticoagulants, antiplatelets and aspirin to treat cardiac disease. New evidence has highlighted the significant and clinically relevant GIB risk. The increased use of aggressive antiplatelet and anticoagulant therapies will alter our current understanding of the epidemiology of GIB. The magnitude of gastrointestinal risk in this vulnerable patient population is still relatively unexplored due to a paucity of literature. This review will highlight changing GIB trends and explore current knowledge regarding GIB risk in cardiac patients. An emphasis on a multidisciplinary approach to the care of these patients will be supported, which involves active patient participation and collaboration between cardiologists and gastroenterologists. Finally, risk-minimization strategies will be suggested and knowledge gaps will be identified.

The quality of antiplatelet and anticoagulant medication administration among ST-segment elevation myocardial infarction patients transferred for primary percutaneous coronary intervention

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.

Incidence and Correlates in the Development of Iatrogenic Femoral Pseudoaneurysm after Percutaneous Coronary Interventions

We aimed to identify the correlates in the development of post-percutaneous coronary intervention (PCI) iatrogenic femoral pseudoaneurysm (IFP). IFP is one of the more common vascular complications of PCI. From February 2008 to June 2012, 10,169 consecutive patients who underwent PCI were retrospectively studied. Patients who developed postprocedural IFP were identified at a single, large tertiary PCI center. One hundred thirty-nine patients developed IFP (1.38%) and were compared to the cohort that did not. Baseline characteristics were comparable, although patients in the IFP group were older and had a higher incidence of insulin-requiring diabetes mellitus and chronic renal insufficiency (68.4 ± 12.9 vs. 65.4 ± 12.3 years, P = 0.004; 23.9% vs. 14.6%, P = 0.002; and 26.6% vs. 17.3%, P = 0.004, respectively). The non-IFP group had more men and a higher use of vascular closure devices, respectively (64.7% vs. 49.6%, P < 0.001; and 54.1% vs. 26.5%, P < 0.001). There was no significant difference in the use of dual antiplatelet or anticoagulation therapies between the 2 cohorts. Univariable correlates for the development of IFP were female gender, insulin-requiring diabetes mellitus, chronic renal insufficiency, and use of manual compression to achieve hemostasis. On multivariable analysis, the successful deployment of vascular closure device for hemostasis reduced the occurrence of IFP (odds ratio 0.31, 95% confidence interval 0.21-0.46, P < 0.0001). The development of IFP following PCI is not uncommon and the appropriate use of vascular closure devices to achieve hemostasis should be encouraged to minimize this vascular complication.

Neutrophil extracellular traps, scholarly debates, and public–private partnerships: highlights of the eighth annual Platelet Colloquium

The first of the Colloquium’s three main sessions included discussion of the rising importance of neutrophil extracellular DNA traps (NETs), which represent an intersection of inflammation, infection, and thrombosis. NETs, a network of DNA fibers, histones, and nuclear proteins produced by nucleosome release from activated neutrophils, are a longrecognized component of the body’s innate immune response to infection. It has recently become apparent, however, that NETs form within blood vessels in response to injury and disease, providing a lattice for red cell adherence, platelet activation, and thrombus formation. Both DNAse and heparin have been shown to disrupt the NET structure, preventing thrombosis. This finding might have relevance in the development of novel therapeutic targets. In addition, the fact that polymers have been shown to bind to cell-free DNA in vitro might hold promise in the development of methods to assess thrombotic risk and status. Also in the first session, the Colloquium brought back a popular segment from 2012, a position debate between two leading researchers. This year’s topic was ‘‘Is There a Role for Antiplatelet Therapy in the Management of Atrial Fibrillation?’’ Arguing in favor was Steven R. Steinhubl, MD, of Geisinger Medical Center, Danville, Pennsylvania; arguing against was Elaine Hylek, MD, of Boston University Medical Center. Table 1 summarizes the main points from both sides of the debate. In the end, the debaters agreed that well-controlled studies will be needed to address many of the knowledge gaps relevant to this question. Session II contemplated the evidence regarding the use of antiplatelet therapies in several high-risk groups, with additional discussions about avenues for future investigation. Despite the available data, substantial knowledge gaps persist for the use of antiplatelet agents in persons with hemoglobinopathies, diabetes, other metabolic disturbances, previous stroke, and deep vein thrombosis. In addition, providers are uncertain about the optimal use of antiplatelet agents during transcatheter aortic valve implantation (TAVI), during ‘‘hybrid’’ coronary procedures, and as a bridge to noncardiac surgery. In Session III, the focus turned to regulatory sciences and governmental support of platelet-related research. Regulatory agencies recognize that the clinical trial ecosystem in the United States is under stress (Table 2). Representatives from the U.S. Food and Drug Administration (FDA) and the National Institutes of Health were on hand to outline the roles that government agencies can play in easing these stressors and facilitating the conduct of high-level research that both addresses public health needs and meets regulatory requirements for therapeutics in the U.S. Specific examples of the new approaches and philosophies embraced by the FDA include implementing new concepts to appropriately P. A. French (&) Chapel Hill, NC, USA e-mail: pat.french@leftlanecomm.com

Ischemic Brain Injury After Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is the second most common cause of stroke and accounts for 8% to 15% of strokes in Western societies with an estimated incidence of 10 to 25 per 100 000 persons.1–3 Despite advances in the field of stroke and neurocritical care,4 the 30-day mortality has not changed significantly over the past 20 years.3 Indeed, ICH has the highest rates of dependence or death among stroke types and proven treatments are lacking. Clinical trials aimed at limiting hemorrhage growth, procoagulant agents for hemostasis,5 and surgical evacuation6 have not translated into improved clinical outcomes. Antihypertensive therapy for the purpose of reducing hematoma growth has been a mainstay of acute management. Guidelines recommend maintaining mean arterial pressure <130 mm Hg during the acute phase7; however, controversies exist given the lack of randomized clinical trial data and uncertainties about the rapidity and target level of blood pressure (BP)-lowering. Recent Phase 2 clinical trials evaluating acute BP control have shown promise in reducing hematoma expansion with an adequate safety profile and Phase 3 trials are underway.8,9 Besides hematoma growth, other pathophysiological processes occur in the setting of ICH and may serve as potential therapeutic targets. In the acute period after ICH, a rapid rise in intracranial pressure (ICP) from an expanding hematoma may reduce cerebral perfusion pressure. In this setting, interventions aimed at BP-lowering and hemostasis may theoretically induce thrombosis or exacerbate brain ischemia, particularly in patients with pre-existing cerebrovascular disease. A recent publication suggests that aggressive BP-lowering may actually cause acute brain ischemia and worsen outcomes after ICH.10 In this review, we outline the data on secondary acute ischemic injury after ICH, review the prevalence of remote ischemic lesions and risk factors associated with their occurrence, explore potential …

Evaluating the Bite of the BARC

Therapeutic options for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI) have evolved significantly over the past decade. In the era when there were limited antithrombotic choices, reduction of ischemic events was the primary goal regardless of the risk of bleeding that was associated with the use of antiplatelet and anticoagulant therapies. In the current era, clinicians are faced with 5 oral antiplatelet options (aspirin, ticlopidine, clopidogrel, prasugrel, and ticagrelor), 3 intravenous antiplatelet agents (abciximab, eptifibatide, and tirofiban), 4 anticoagulants (unfractionated heparin, low-molecular-weight heparin, bivalirudin, and fondaparinux), and potentially additional oral anticoagulants for long-term secondary prevention.1 In general, the iterations in antithrombotic drugs have been directed at achieving greater potency; however, some agents, like fondaparinux and bivalirudin, were developed specifically in the context of maintaining antithrombotic efficacy but with better safety (ie, lower bleeding risk).2,3 The focus on bleeding risk is a relatively new development and is probably driven by the robust literature demonstrating an association between bleeding during the management of ACS or in the setting of PCI and subsequent short- and long-term adverse outcomes, such as myocardial infarction, stroke, stent thrombosis, and death.4,5 Given these risks, guidelines for ACS and PCI recommend assessing bleeding risk before starting therapy, ostensibly to identify patients at high risk of bleeding and subsequently to choose therapeutic approaches that are associated with lower bleeding risk.6 Although this approach appears reasonable, attempting to determine the relative safety of different anticoagulant and antiplatelet options is challenging because of the lack of direct comparative studies and the significant heterogeneity in the way bleeding is defined across clinical trials. Article see p 1424 There are no less than 10 distinct bleeding definitions used in clinical trials and registries of ACS patients.7 These definitions …