Use Of Antiplatelet Therapies Research Articles

Cancer-Associated Stroke: Thrombosis Mechanism, Diagnosis, Outcome, and Therapeutic Strategies.

Cancer can induce hypercoagulability, which may lead to stroke. This occurs when tumor cells activate platelets as part of their growth and metastasis. Tumor cells activate platelets by generating thrombin and expressing tissue factor, resulting in tumor cell-induced platelet aggregation. Histopathological studies of thrombi obtained during endovascular thrombectomy in patients with acute stroke and active cancer have shown a high proportion of platelets and thrombin. This underscores the crucial roles of platelets and thrombin in cancer-associated thrombosis. Cancer-associated stroke typically occurs in patients with active cancer and is characterized by distinctive features. These features include multiple infarctions across multiple vascular territories, markedly elevated blood D-dimer levels, and metastasis. The presence of cardiac vegetations on echocardiography is a robust indicator of cancer-associated stroke. Suspicion of cancer-associated stroke during endovascular thrombectomy arises when white thrombi are detected, particularly in patients with active cancer. Cancer-associated stroke is almost certain when histopathological examination of thrombi shows a very high platelet and a very low erythrocyte composition. Patients with cancer-associated stroke have high risks of mortality and recurrent stroke. However, limited data are available on the optimal treatment regimen for stroke prevention in these patients. Thrombosis mechanism in cancer is well understood, and distinct therapeutic targets involving thrombin and platelets have been identified. Therefore, direct thrombin inhibitors and/or antiplatelet agents may effectively prevent stroke recurrence. Additionally, this strategy has potential benefits in cancer treatment as accumulating evidence suggests that aspirin use reduces cancer progression, metastasis, and cancer-related mortality. However, clinical trials are necessary to assess the efficacy of this strategy involving the use of direct thrombin inhibitors and/or antiplatelet therapies.

Antithrombotic therapy and spinal surgery: a retrospective cohort study of 289 consecutive elderly patients with degenerative lumbar stenosis.

Lumbar spinal stenosis (LSS) is a disabling degenerative process of the spine, mainly affecting older patients. LSS manifests with low-back and leg pain and neurogenic claudication. Disability and impairment in activities of daily living are consequences of the progressive narrowing of the lumbar spinal canal. Surgical decompression has been shown to be superior to conservative management. Nonetheless, intraoperative and postoperative blood loss in elderly patients taking antiplatelet or anticoagulant drugs owing to cardiovascular comorbidities may be a special issue. This study describes and compares early outcomes after surgical procedures in different groups of patients receiving antithrombotic drugs. The authors' study retrospectively recruited 289 consecutive patients aged ≥ 65 years who received lumbar decompression for spinal stenosis between January 2021 and May 2022. First, 183 patients taking antiplatelet therapy were divided into two groups according to the rationale for use: primary versus secondary prophylaxis of cardiovascular events (group 1 vs group 2). Primary prevention was stopped preoperatively, or secondary prevention was not discontinued during the perioperative period. Secondly, 106 patients who were not taking antiplatelet mediation were divided into two groups, depending on whether preoperative low-molecular-weight heparin had not been administered or had been (group A vs group B). Intraoperative blood loss, surgical time, and postoperative hospitalization were analyzed. No significant statistical differences were observed between groups 1 and 2 in terms of intraoperative blood loss and time of surgery, or between groups A and B in terms of all analyzed variables. No early or delayed complications were observed, perioperatively or during the postoperative 3-month follow-up period. The results of this study suggest that the use of anticoagulant and antiplatelet therapies in elective decompressive surgery could be devoid of early complications and could be safely continued perioperatively.

Limb Salvage after Covid-19 Related Major Arterial Thrombosis in an 81 -Year Lady with Critical Limb Ischemia: A Case Report

Hypercoagulable state and thromboembolic events are common extra-pulmonary complications of COVID-19 that are increasingly reported in the literature. Unfortunately unlike VTE, no remarkable data are available on arterial thrombosis in SARS-CoV2 infected patients, and despite the use of anticoagulant and antiplatelet therapies, severe arterial thrombotic complications are observed. The objective of this case study is to share our experience about COVID-19 related peripheral arterial thrombosis and highlight the management plan of the resulting CLI in an elderly patient. It is a case report of an 81- year lady that developed fever, vomiting, and bone aches for 3 days before being transferred to the fever hospital with gastrointestinal upset, where she was admitted to normal ward and the diagnosis of COVID-19 was confirmed by RT-PCR. The patient improved and discharged to home after one week, 5 days later she started to complain of painful right foot then the pain involved the whole leg later on with fixed color changes and coldness, however, the diagnosis of acute ischemia was missed for one week more until the patient came to our department, and arterial duplex revealed extensive thrombosis of the SFA, popliteal and tibial arteries with CLI (ABI was<0.4). The patient was prepared for prompt vascular intervention and surgical embolectomy was performed via combined popliteal and femoral approaches. A long, thick, more gelatinous and darker thrombus was retrieved both proximally and distally. The limb was saved with fairly good distal runoff. Unfortunately, one week after the operation the patient slipped and developed fracture neck femur of the same limb, and she was operated on one month later. The patient had uneventful postoperative course, and such lucky 81years lady kept a viable well-functioning limb and could walk again. In conclusion, the key points of our case study include vigilant consideration of the arterial thrombosis in COVID-19 infected patients, routine monitoring of D-dimer levels with initiation of full-dose anticoagulation if levels elevated by six times the upper limit of normal, as well as prompt diagnosis of ALI, and urgent surgical revascularization to save the limb.

Association of COVID-19 outcomes with diabetes in the Veneto region (north-east italy): Epidemiological insights for the endemic phase?

Background and aimsDiabetes mellitus is a prevalent chronic disease in patients who die of COVID-19. The aim of this study was to investigate the clinical and metabolic characteristics of diabetic patients with COVID-19 during the pre-vaccination phase. Methods and resultsA retrospective cohort study was conducted from February 2020 to February 2021 to examine the clinical and metabolic profiles of unvaccinated diabetic patients affected by COVID-19. Data were collected from claim databases, hospital discharge records, and clinical records within a healthcare district located in northeastern Italy with a population of 936,000. Potential prognostic indicators including sex, age, Body Mass Index (BMI), duration and type of diabetes, metabolic control, and the use of antidiabetic, antihypertensive, lipid-lowering, and antiplatelet therapies were investigated. For hospitalized patients, additional variables were recorded, such as length of hospital stay, blood pressure at admission, comorbidities, D-dimer levels, blood glucose (BG), in-hospital insulin and corticosteroid therapies, requirement for mechanical ventilation (i.e., orotracheal or tracheostomy), admission to the Intensive Care Unit (ICU), and mortality. Diabetic patients hospitalized for COVID-19 with a poorer prognosis were characterized by advanced age, longer diabetes duration, hypertension, higher usage of sulfonylureas, and lower usage of dietotherapy alone, metformin, Glucagon-Like Peptide-1 Receptor agonists (GLP1-Ra), and Renin-Angiotensin-Aldosterone System inhibitors (RAAS-i). ConclusionConsidering the potential for COVID-19 to become endemic, special care should be taken in managing older diabetic patients’ treatments.

Postoperative major bleeding risk in patients using oral antiplatelets and/or anticoagulants after laparoscopic gastric cancer surgery.

The use of antiplatelet and/or anticoagulant therapies has become common. In rare cases, these therapies may increase the risk of dangerous postoperative bleeding. We investigated the association of antiplatelets and/or anticoagulants with postoperative major bleeding risk in laparoscopic gastric cancer surgery. We retrospectively enrolled 3,663 gastric cancer patients (antiplatelet/anticoagulant group, 518; control group, 3,145) who had undergone laparoscopic surgery between January 2012 and December 2017. To minimize selection bias, 508 patients in each group were matched using propensity score matching (PSM) method. The primary outcome was postoperative major bleeding. Secondary outcomes were intraoperative, postoperative transfusion and early complications. After PSM, postoperative major bleeding occurred in 10 (2.0%) and 3 cases (0.6%) in the antiplatelets/anticoagulants and control groups, respectively (P = 0.090). Intraoperative and postoperative transfusions were not significantly different between 2 groups (2.4% vs. 1.4%, P = 0.355 and 5.5% vs. 4.3%, P = 0.469). Early complications developed in 58 (11.4%) and 43 patients (8.5%) in the antiplatelets/anticoagulants and control groups, respectively (P = 0.142). The mean amounts of intraoperative and postoperative transfusions were not significantly different between the groups (366.67 ± 238.68 mL vs. 371.43 ± 138.01 mL, P = 0.962; 728.57 ± 642.25 mL vs. 508.09 ± 468.95 mL, P = 0.185). In multivariable analysis, male (P = 0.008) and advanced stage (III, IV) (P = 0.024) were independent significant risk factors for postoperative major bleeding. Preoperative antiplatelets and/or anticoagulants administration did not significantly increase the risk of postoperative major bleeding after laparoscopic gastric cancer surgery.

Acquired Haemophilia A: A Review of What We Know.

Autoantibodies against plasma coagulation factors could be developed by some individuals inducing severe and sometimes fatal bleedings. This clinical entity is called acquired haemophilia. It should be suspected in subjects with acute abnormal bleedings, without personal or familiar history of congenital bleeding disorders with an unexplained prolonged aPTT. It is rare disease, although its incidence may be underestimated due to the low knowledge about it by many specialists, the frequent use of anticoagulant or antiplatelet therapies in the affected population that can mask the diagnosis and, sometimes, a so withering effect that avoid its confirmation. Mortality ranges between 9% and 33% depending on the series in the first 2 months after diagnosis. This mortality is attributed in up to 40% of the cases to infections in the context of immunosuppressive treatments used to eliminate the inhibitor. Factor VIII levels below 1% and high inhibitor titers are conditions of worse response rates. Advanced age, patient's ECOG, and underlying conditions are key prognostic factors for response to treatment and patient survival. To reduce morbidity and mortality in these patients, it is important to have clinical knowledge and access to guidelines to achieve an early diagnosis and to optimize the haemostatic and immunosuppressive treatment. This review aims to contribute to the dissemination of basic concepts on the epidemiology etiopathogenesis, diagnosis, treatment and management of these patients, as well as risk factors to get remission and the longest overall survival to allow individualized care. Especial awareness will be proposed in patients with some underlying conditions like cancer, autoimmune diseases, children, pregnancy or drugs.

Bleeding Outcomes in People with Von Willebrand Disease Receiving Antithrombotic Therapy

▪Aging brings additional challenges in the management of people with von Willebrand Disease (VWD). Plasma von Willebrand Factor (VWF) levels may increase but the impact on bleeding phenotype is unclear. With the development of age-related comorbidities, the use of antiplatelet (AP) or anticoagulant (AC) therapies may be warranted. As highlighted in the 2021 international VWD guidelines, limited evidence exists regarding the bleeding risk and safety of AP/AC use in people with VWD. 1 We sought to address this knowledge gap through a retrospective review of a large cohort of people with VWD attending a tertiary referral center.The records of all patients aged >50 years (y) attending our center registered with VWD were retrospectively reviewed. We identified all individuals treated with AP and/or AC, recording the indication for and duration of therapy. We also recorded disease subtype, baseline and most recent plasma VWF levels and bleeding on AP and/or AC. Bleeding episodes were stratified according to the World Health Organization (WHO) Bleeding Scale.From 255 eligible patients, 18 patients (7 male, 11 female) were identified who received AP and/or AC over a period of 22y. The median age at commencement was 60.2 years (range 40.0-74.5). 15 patients had Type 1 with baseline levels 30-50 IU/dL, (median VWF antigen, VWF:Ag, 57.5, range 39-87 IU/dL; median VWF ristocetin cofactor levels, VWF:RCo, 43, range 35-54 IU/dL). 3 patients had type 2 VWD (median VWF:Ag 64, range 27-90 IU/dL; median VWF:RCo of 16, range 10-66 IU/dL). The type of AP/AC used and indications for treatment are outlined in Table 1.Overall, 12 patients were treated with AP and 7 with AC therapy (19 therapies in total as one patient received first aspirin then warfarin therapy). The cumulative exposure to AP therapy was 61.9y with a median exposure time of 3.2y/patient (range 0.3-14.1y). Duration of AC therapy was shorter, with a cumulative exposure of 17.6y and a median of 1.5 y/patient (range 0.3-6.3y).Overall, 85.7% of patients on AC therapy had at least one episode of bleeding (6/7; 10 episodes total) in contrast to 58.3% of patients on AP (7/12; 12 episodes total). Of these 22 episodes, 5 (22.7%) were grade 1 bleeding. Grade 2 bleeding (iron deficiency or gastrointestinal (GI), gynecological or genitourinary bleeding) occurred in 5 patients (41.7%) treated with AP and 4 patients (57.1%) on AC (total of 14 episodes). 1 episode of grade 3 bleeding occurred in both the AP (8.3%) and AC (14.3%) group (GI bleeding requiring transfusion and abdominal hematoma respectively). The single grade 4 bleed was an intracranial hemorrhage (ICH) and occurred in a patient with type 2 VWD (VWF:RCo 10 IU/dL) on warfarin for atrial fibrillation; this required prothrombin complex concentrate, VWF concentrate, neurosurgical intervention and cessation of AC.Bleeding complications resulted in discontinuation of therapy in 2 patients (11.1%) treated; the individual with ICH and a patient with type 1 VWD on warfarin (baseline VWF:RCo 43 IU/dL) due to recurrent GI bleeding. No patients treated with AP therapy required discontinuation of use. The overall rate of major bleeding (WHO grade >/=3) in our study was 11.4 events/100 patient-years in VWD patients receiving AC therapy, in comparison to the rate of bleeding in the general population using AC of 7.2 events per 100 patient-years. 2For patients with type 1 VWD, plasma VWF levels were seen to increase during follow up (median 8.5y, VWF:Ag median +13 IU/dL, VWF:RCo +18 IU/dL), resulting in plasma VWF levels >50 IU/dL for 66.6% of patients in this cohort. Despite this, bleeding while on AP and/or AC was still experienced in 8/10 patients whose levels had normalized, necessitating cessation in one instance.In conclusion, this study provides important insights into the use of AP and/or AC in patients with VWD. Bleeding rates were higher in patients treated with AC therapy than AP resulting in cessation of therapy in 28.6% of those on AC. Bleeding events still occurred despite normalization of plasma VWF levels in patients with type 1 VWD. These data highlight the need for close follow up of patients with VWD whilst on antithrombotic therapy, particularly AC.1. Connell NT et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv 2021;5(1):301-325.2. Shoeb M, Fang M. Assessing Bleeding Risk in Patients Taking Anticoagulants. J Thromb Thrombolysis 2013;35(3):312-319. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

PCV44 Real-World Assessment of the Use of Anti-platelet Therapy for Recurrent Stroke Prevention in US Patients without Atrial Fibrillation with Recent Ischemic Stroke or Transient Ischemic Attack

Antiplatelet (AP) therapies are the recommended treatment for prevention of recurrent stroke. However, bleeding is a significant risk with any AP therapy. Data on the real-world use of AP therapies in the prevention of recurrent stroke is lacking. This study evaluated current AP treatment patterns in a real-world setting following an initial ischemic stroke (IS) or transient ischemic attack (TIA).

Coronary revascularization in patients with stable coronary disease and diabetes mellitus.

Purpose of Study:Diabetes mellitus accelerates the development of atherosclerosis. Patients with diabetes mellitus have higher incidence and mortality rates from cardiovascular disease and undergo a disproportionately higher number of coronary interventions compared to the general population. Proper selection of treatment modalities is thus paramount. Treatment strategies include medical management and interventional approaches including coronary artery bypass graft (CABG) surgery and percutaneous coronary interventions (PCI). The purpose of this review is to assimilate emerging evidence comparing CABG to PCI in patients with diabetes and present an outlook on the latest advances in percutaneous interventions, in addition to the optimal medical therapies in patients with diabetes.Key Methods:A systematic search of PubMed, Web of Science and EMBASE was performed to identify prospective, randomized trials comparing outcomes of CABG and PCI, and also PCI with different generations of stents used in patients with diabetes. Additional review of bibliography of selected studies was also performed.Main Conclusions:Most of the trials discussed above demonstrate a survival advantage of CABG over PCI in patients with diabetes. However, recent advances in PCI technology are starting to challenge this narrative. Superior stent designs, use of specific drug-eluting stents, image-guided stent deployment, and the use of contemporary antiplatelet and lipid-lowering therapies are continuing to improve the PCI outcomes. Prospective data for such emerging interventional technologies in diabetes is however lacking currently and is the need of the hour.

A predictive nomogram of bleeding risk in patients with atrial fibrillation after drug-eluting stent implantation.

BackgroundThe use of anticoagulants and antiplatelet therapies is associated with a higher risk of bleeding in atrial fibrillation (AF) patients after percutaneous coronary intervention, especially after stent implantation. However, no accurate bleeding risk prediction tool has been developed for these patients. The aim of this study was thus to establish a bleeding risk prediction model (predictive nomogram) for patients with AF after stent implantation.MethodsConstruction of the predictive nomogram was based on a retrospective study, which enrolled 943 AF patients who underwent drug-eluting stent implantation between May 2012 and September 2016. A range of factors, including demographics, comorbidities, medication strategies, arterial access, and laboratory tests, were collected as baseline data. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were used to identify the key clinical features for construction of the predictive nomogram. The concordance index (C-index) and internal validation were used to evaluate the efficacy of the nomogram.ResultsOf the 943 AF patients that underwent stent implantation, the occurrence of bleeding events was 8.2% (77 out of 943). Key predictors included the number of antiplatelet drugs, peptic ulcer, cerebral infarction, type 2 diabetes, thrombocytopenia, anemia, prior myocardial infarction, sex (male), use of anticoagulant drugs, liver dysfunction, hypertension, and acute myocardial infarction. These predictors were used to construct the nomogram. The C-index for the prediction of bleeding risk by the nomogram was 0.841 (95% CI: 0.79–0.89), which indicated good discrimination and calibration. The C-index of internal validation was 0.795, which demonstrated good efficacy of the model.ConclusionsThis study suggests that our novel nomogram can accurately predict bleeding risk in AF patients after stent implantation during hospitalization, thereby helping to avoid complications. The nomogram may also be helpful for the creation of individualized post-discharge medication strategies.

Pre-procedural predictive factors of symptomatic intracranial hemorrhage after thrombectomy in stroke.

Symptomatic intracerebral hemorrhage (sICH) is a common complication of acute ischemic stroke (AIS) associated with limited treatments and poor outcomes. We aimed to identify predictive factors of sICH in patients with AIS following mechanical thrombectomy (MT) in a real-world setting. Patients with large vessel occlusion of the anterior circulation treated with MT were consecutively included in a prospective monocentric cohort. Clinical, biological, and radiological parameters were collected to identify pre-procedural predictors for sICH. 637 patients were included in our study. Magnetic resonance imaging was performed on most patients (86.7%). sICH occurred in 55 patients (8.6%). 428 patients (67.2%) were treated with intravenous thrombolysis. After multivariate analysis, prior use of antiplatelet therapies (odd ratio (OR) 1.84, 95% confidence interval (CI) 1.01-3.32), high C-reactive protein (OR per standard deviation (SD) increase 1.28, 95% 1.01-1.63), elevated mean arterial blood pressure (OR per 10mmHg increase 1.22, 95% CI 1.03-1.44), hyperglycemia (OR per one SD-log increase 1.38, 95% CI 1.02-1.87), and low ASPECTS (OR per 1-point decrease 1.42, 95% CI 1.12-1.80) were found to be independent predictive factors of sICH. The pre-procedural predictors did not change when the absence of successful recanalization was considered as a covariate. Patients with strokes of unknown onset time were not especially vulnerable for sICH. sICH after MT was associated with several pre-procedural risk factors: prior use of antiplatelet therapies, high C-reactive protein and hyperglycemia at baseline, elevated mean arterial blood pressure, and low ASPECTS.

Post-infarct left ventricular thrombosis is mechanistically related to ventricular wall rupture

Left ventricular thrombus (LVT) after acute myocardial infarction (AMI) remains to be a common complication bearing adverse prognostic implication. Majority of LVT occurs within the first week after AMI. Over decades, the regional stasis of blood flow is regarded as the main reason for LVT formation. Here we hypothesize that LVT developed within the first week after AMI is the consequence of an incomplete wall rupture. Endocardial rupture with exposure of infarcted tissues triggers platelet thrombosis within the rupture site and then the thrombus grows towards the ventricular chamber forming LVT. This hypothesis is implicated by the comparable clinical features of patients with LVT or with cardiac rupture, and supported by experimental findings in murine model of AMI revealing the mechanistic link between rupture and LVT. This hypothesis, if confirmed, would improve our understanding on the pathophysiology of both rupture and LVT as two pivotal mechanical complications after AMI, and the role of platelets in the setting of AMI and hence the use of anti-platelet therapies. Future studies are warranted to test this hypothesis by serial cardiac imaging on AMI patients with high risk of LVT.

Bleeding Severity in Percutaneous Coronary Intervention (PCI) and Its Impact on Short-Term Clinical Outcomes.

Bleeding severity in patients undergoing percutaneous coronary intervention (PCI), defined by the Bleeding Academic Research Consortium (BARC), portends adverse prognosis. We analysed data from 37,866 Australian patients undergoing PCI enrolled in the Victorian Cardiac Outcomes Registry (VCOR), and investigated the association between increasing BARC severity and in-hospital and 30-day major adverse cardiac and cerebrovascular events (MACCE) (a composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, or stroke). Independent predictors associated with major bleeding (BARC groups 3&5), and MACCE were also assessed. There was a stepwise increase in in-hospital and 30-day MACCE with greater severity of bleeding. Independent predictors of bleeding included female sex (Odds Ratio (OR) 1.34), age (OR 1.02), fibrinolytic therapy (OR 1.77), femoral access (OR 1.51), and ticagrelor (OR 1.42), all significant at the p < 0.001 level. Following adjustment of clinically important variables, BARC 3&5 bleeds (OR 4.37) were still predictive of cumulative in-hospital and 30-day MACCE. In conclusion, major bleeding is an uncommon but potentially fatal PCI complication and was independently associated with greater MACCE rates. Efforts to mitigate the occurrence of bleeding, including radial access and judicious use of potent antiplatelet therapies, may ameliorate the risk of short-term adverse clinical outcomes.

Embolisation of Epigastric Artery in a Massive Rectus Sheath Hematoma After Cardiac Valvular Surgery

Increasing use of antiplatelet and anticoagulant therapies has led to a concomitant increase in the incidence of rectus sheath hematoma. Herein, we report a 55-year-old patient of massive rectus sheath hematoma and ongoing bleeding into the left rectus sheath presenting with epigastric pain and hemodynamic involvement who underwent triple valve surgery three weeks ago. The bleeding vessel of the superior epigastric artery was detected by emergency selective angiographic imaging of the left internal mammarian artery, and embolization was performed successfully. Complete absorption of the hematoma was proven by computed tomography after 19 months.

Pharmacokinetics of Ticagrelor in Infants and Toddlers Aged

Pharmacokinetics of Ticagrelor in Infants and Toddlers Aged <24 Months with Sickle Cell Disease

PREDICTORS OF DAPT USE IN PATIENTS BEYOND 1 YEAR POST MYOCARDIAL INFARCTION: INSIGHTS FROM THE TIGRIS OBSERVATIONAL STUDY

International guidelines vary in their recommendations for dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI). In the current analysis, we sought to identify predictors of DAPT use in patients ≥1 year post-MI prior to publication of the DAPT score and the most recent iterations of international guidelines for the use of DAPT in the management of patients with MI. TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 25 countries), observational study of patients 1 to 3 years post-MI between June 2013 and November 2014. We performed a multivariable logistic regression analysis to identify independent predictors of DAPT use at 396 days post-MI (365 days plus a 31-day overrun period to allow intended DAPT discontinuation at 1 year). Patients on oral anticoagulation or on treatment with ticagrelor were excluded. Of 8464 patients enrolled (mean age 66 years, women 24%, ST-elevation MI 53%, prior MI 10%, multivessel disease 66%), the index MI was managed with a percutaneous coronary intervention in 82% of patients, coronary artery bypass grafting in 7%, and medically in 11%. The prevalence of DAPT use was 78% at the time of hospital discharge and 40% at 396 days post-MI. There was significant variability in practice patterns of DAPT use post-MI across the different geographical regions (Figure). In the subset of patients on DAPT at 396 days post-MI, aspirin was combined with clopidogrel in 84%, prasugrel in 12%, and other antiplatelet agents in 4%. DAPT use at 396 days post-MI was independently associated with geographic region, age, use of PCI for the index MI, and a history of multivessel disease or angina (Table). Several variables included in the DAPT score and addressed in international guideline recommendations for the use of antiplatelet therapies (e.g. diabetes, second prior MI, hypertension, peripheral artery disease, heart failure, smoking, and renal insufficiency) were not independent predictors of DAPT use at 396 days. DAPT use declined from hospital discharge to 1 year post-MI. Overall, DAPT use ≥1 year post-MI was prevalent and appeared to be influenced by regional practices. Further research is needed to determine how the DAPT score and international guidelines have affected long-term DAPT use practice patterns.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clinical trials in long-term antiplatelet therapies: focus on the role of aspirin.

The purpose of this review is to summarize the existing evidence for use of long-term antiplatelet therapies for primary and secondary prevention of adverse cardiovascular events. In the setting of primary prevention, several contemporary trials have shown a lack of net clinical benefit with use of aspirin across different patient groups, including those with diabetes mellitus, older age or high estimated cardiac risk. For secondary prevention, the addition of either ticagrelor or low-dose rivaroxaban to aspirin monotherapy significantly lowered recurrent vascular events, albeit with excess bleeding. Aspirin withdrawal did not result in excess thrombotic risk or less bleeding among patients undergoing percutaneous coronary intervention (PCI) treated with ticagrelor. In the contemporary era, routine use of aspirin is not beneficial in the majority of patients free of cardiac disease. In contrast, for secondary prevention, aspirin monotherapy is not sufficient to lower recurrent vascular risk. Antiplatelet monotherapy with ticagrelor may emerge as an alternative to lower bleeding whereas maintaining ischemic efficacy in selected patients undergoing PCI.

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.