Secondary Prevention Of Thrombotic Events Research Articles

Values and Preferences Towards Antithrombotic Therapy in Patients with Myeloproliferative Neoplasms: A Qualitative Study

Background: Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET), confer a high risk for thrombotic events. The primary and secondary prevention of thrombotic events is managed with antithrombotic therapy, which is complicated by a high frequency of bleeding in Ph- MPN patients. When making shared decisions about antithrombotic therapy, physicians and patients must weigh thrombotic and bleeding risks and their consequences. However, little is known about the preferences and perceptions of patients with MPNs regarding antithrombotic therapy. The objectives of this study were therefore to identify: 1) patient-important factors and 2) barriers and facilitators to the use of antithrombotic therapy as thromboprophylaxis among patients with MPNs. Methods: In this qualitative study, semi-structured focus groups (FGs) were conducted with people diagnosed with PV and ET recruited via email from Canadian MPN Patient Support Groups. Focus groups were stratified based on previous history of a bleed requiring medical attention, previous history of thrombosis, or no history of bleeding or thrombosis. Open-ended questions and probes were used to guide FG discussions and FGs concluded with a polling exercise in which participants selected the most important facilitators and barriers to antithrombotic medication use. Data were analyzed using thematic analysis and the techniques of the Framework Method (Gale et al., 2013). Two team members independently reviewed and coded FG audio transcripts using NVivo to develop a coding framework. Coding comparison queries were run to assess agreement, discussion was used to resolve discrepancies, and the coding framework was iteratively refined. Data were reviewed by two members of the study team and preliminary themes were identified, guided by the research objectives. Results: We present preliminary results of our analysis. Four FGs were conducted with a total of 18 participants (range 3-6 participants). The average age of participants was 59 years, 13 (72%) were female and 10 (56%) had ET. Participants were taking aspirin (16/18, 89%), warfarin (1/18, 5%), and apixaban (1/18, 5%). Three participants (17%) had a prior thrombotic event, (ischemic stroke, myocardial infarction, and splanchnic vein thrombosis), and 3 (17%) had a prior bleeding event (epistaxis, gastrointestinal [GI] bleeding). The most important factors identified for taking antithrombotic therapy were preventing thrombotic events (94%) and a physician's recommendation (83%). Many participants perceived there was no choice when it came to the decision to use antithrombotic therapy; rather it was a physician-prescribed, necessary treatment to prevent thrombosis. Perceived downsides to antithrombotic therapy included the higher risk of bleeding, prolonged bleeding, and bruising, with specific concern about the visibility of bruises. Several participants also voiced concerns about the impact of long-term aspirin use on GI health and the potential for ulcer formation. A few participants reported lowering their dose of aspirin, as per physician recommendations or by self-adjusting the dose based on concerns about GI bleed risk. However, some participants did not perceive any downsides to using antithrombotic therapy or considered that the benefits outweighed the risks, while others were less certain. Additional analyses are underway. Conclusion: Patients with MPNs accept antithrombotic therapy use, motivated by trust in their physician's recommendations and the desire to prevent a stroke or myocardial infarction. While these values and preferences align with PV and ET treatment guidelines, it is important to recognize the influence that physician recommendations have on patients' perceptions towards antithrombotic therapy in the shared decision-making process.

Does the continuation of low-dose acetylsalicylic acid during the perioperative period of thyroidectomy increase the risk of cervical haematoma? A 1-year experience of two Italian centers.

A growing number of patients taking antiplatelet drugs, mainly low-dose acetylsalicylic acid (ASA) (75-150 mg/day), for primary or secondary prevention of thrombotic events, are encountered in every field of surgery. While the bleeding risk due to the continuation of these medications during the perioperative period has been adequately investigated in several surgical specialties, in thyroid surgery it still needs to be clarified. The main aim of this study was to assess the occurrence of cervical haematoma in patients receiving low-dose acetylsalicylic acid, specifically ASA 100 mg/day, during the perioperative period of thyroidectomy. Patients undergoing thyroidectomy in two high-volume thyroid surgery centers in Italy, between January 2021 and December 2021, were retrospectively analysed. Enrolled patients were divided into two groups: those not taking ASA were included in Group A, while those receiving this drug in Group B. Univariate analysis was performed to compare these two groups. Moreover, multivariate analysis was employed to evaluate the use of low-dose ASA as independent risk factor for cervical haematoma. A total of 412 patients underwent thyroidectomy during the study period. Among them, 29 (7.04%) were taking ASA. Based on the inclusion criteria, 351 patients were enrolled: 322 were included in Group A and 29 in Group B. In Group A, there were 4 (1.24%) cervical haematomas not requiring surgical revision of haemostasis and 4 (1.24%) cervical haematomas requiring surgical revision of haemostasis. In Group B, there was 1 (3.45%) cervical haematoma requiring surgical revision of haemostasis. At univariate analysis, no statistically significant difference was found between the two groups in terms of occurrence of cervical haematoma, nor of the other early complications of thyroidectomy. At multivariate analysis, the use of low-dose ASA did not prove to be an independent risk factor for cervical haematoma. Based on our findings, we believe that in patients receiving this drug, either for primary or secondary prevention of thrombotic events, its discontinuation during the perioperative period of thyroidectomy is not necessary.

Untangling the difficult interplay between ischemic and hemorrhagic risk: The role of risk scores.

BACKGROUNDBleedings are an independent risk factor for subsequent mortality in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention. This represents a hazard equivalent to or greater than that for recurrent ACS. Dual antiplatelet therapy (DAPT) represents the cornerstone in the secondary prevention of thrombotic events, but the benefit of such therapy is counteracted by the increased hemorrhagic complications. Therefore, an early and individualized patient risk stratification can help to identify high-risk patients who could benefit the most from intensive medical therapies while minimizing unnecessary treatment complications in low-risk patients. AIMTo review existing literature and gain better understanding of the role of ischemic and hemorrhagic risk scores in patients with ischemic heart disease (IHD). METHODSWe used a combination of terms potentially used in literature describing the most common ischemic and hemorrhagic risk scores to search in PubMed as well as references of full-length articles.RESULTSIn this review we briefly describe the most important ischemic and bleeding scores that can be adopted in patients with IHD, focusing on GRACE, CHA2DS2-Vasc, PARIS CTE, DAPT, CRUSADE, ACUITY, HAS-BLED, PARIS MB and PRECISE-DAPT score. In the second part of this review, we try to define a possible approach to the IHD patient, using the most suitable scores to stratify patient risk and decide the most appropriate patient treatment. CONCLUSIONIt becomes evident that risk scores by themselves can’t be the solution to balance the ischemic/bleeding risk of an IHD patient. Instead, some risk factors that are commonly associated with an elevated risk profile and that are already included in risk scores should be the focus of the clinician while he/she is taking care of a patient affected by IHD.

Effectiveness and Safety of the Direct Oral Anticoagulants in Low-Risk Antiphospholipid Syndrome: A Case Series

Introduction: Thrombotic Antiphospholipid syndrome (TAPS) is an autoimmune condition where venous thromboembolism (VTE) and/or arterial thromboembolism (ATE) occurs in the presence of antiphospholipid antibodies (aPLs). TAPS is traditionally managed with long-term anticoagulation with vitamin K antagonists (VKA). Over the past decade, direct oral anticoagulants (DOACs) have been increasingly replacing VKAs as the oral anticoagulant of choice given their lower risk of bleeding, fixed dosing, and no requirement for routine monitoring. However, recent evidence has demonstrated inferiority of DOACs compared to VKAs in TAPS patients with high risk (triple positive) aPL profiles or previous arterial events. It remains unclear whether TAPS patients with low risk aPL profiles (single positive), and without previous ATE, can be treated effectively and safely with DOACs. Objectives: To assess the effectiveness and safety of DOACs at preventing recurrent VTE or ATE in TAPS patients with a low risk aPL profile, and without prior ATE. Methods: We conducted a retrospective review of all TAPS patients with a low risk aPL profile, without prior ATE, who were anticoagulated with a DOAC at two tertiary care hospitals in Toronto, Canada from January 2010 to July 2020. All patients with any positive aPL test results were first identified through the laboratory information system. This list was cross referenced with patients seen in specific thrombosis clinics and confirmed through individual electronic chart review. TAPS was defined as persistent (>12 weeks apart) lupus anticoagulant (LA) positivity, anti-cardiolipin titre (ACA) >40 GPL, or anti-2-glycoprotein 1 titre (a2GP1) >40 GPL, with a preceding thrombotic event. Patients were excluded if any of the aPLs were deemed to be simultaneously positive or if there was a history of previous ATE. a2GP1 was not systematically tested in all patients. Patient outcomes were assessed throughout the duration of anticoagulation with a DOAC. Recurrent VTE included deep vein thrombosis, pulmonary embolism, or VTE of atypical location, and required objective confirmation with appropriate diagnostic imaging. ATE included ischemic stroke, transient ischemic attack (TIA), myocardial infarction, or other systemic arterial embolism. Major bleeding (MB) and clinically relevant non major bleeding (CRNMB) were defined by International Society on Thrombosis and Hemostasis criteria. Results: 1195 patients were identified with at least one instance of single positive aPL who had been seen in one of the thrombosis clinics. Patients were excluded for the following reasons: 858 for non-persistent aPL positivity, 70 for simultaneous aPL positivity, 20 for a likely false positive LA due to DOAC therapy, 93 due to an absence of preceding VTE, 45 for history of previous ATE, and 59 due to no prior DOAC therapy. After exclusions, 50 patients were included in the analysis, encompassing 157.2 years of patient-follow up. The study population was comprised of 24 women and 26 men with a mean age of 49.6 (standard deviation (SD) 16.3)years at the start of DOAC therapy (Table 1). The mean duration of DOAC treatment was 37.7 (SD 23.8) months. Fifteen (30%) patients had prior diagnosis of systemic lupus erythematosus (SLE), while 4 (8%) had other systemic autoimmune disease diagnoses. Only 1 patient met criteria for obstetric APS, on the basis of 3 consecutive fetal losses before 10 weeks gestation. None of the patients had documented valvular disease or thrombocytopenia. All patients were treated initially with therapeutic dose rivaroxaban, although 6 (12%) patients were switched to therapeutic dose apixaban due to increased bruising or menorrhagia. Five patients on rivaroxaban and 3 patients on apixaban were switched to a reduced dose DOAC. No patient had recurrent VTE. One patient had a possible ATE as a TIA, presenting with an episode of loss of sight for 15 minutes while on reduced dose apixaban. None of the patients experienced MB. Two patients experienced CRNMB, both severe menorrhagia, one on therapeutic dose of rivaroxaban and the other patient on reduced dose of rivaroxaban. Conclusions: In our retrospective case series of 50 patients with TAPS, a low risk aPL profile and no previous ATE, DOACs were effective and safe in the secondary prevention of thrombotic events with no MB. Larger, prospective controlled studies are required to confirm these findings. Disclosures No relevant conflicts of interest to declare.

Management of Antiphospholipid Syndrome in Patients with Systemic Lupus Erythematosus

Purpose of review To provide an approach to primary and secondary prevention of thrombotic events and obstetric complications in patients with antiphospholipid antibodies (aPL) with or without antiphospholipid syndrome (APS), particularly in association with systemic lupus erythematosus (SLE).

Use of Rivaroxaban for Prophylaxis of Superficial Venous Thrombosis in Klippel-Trenaunay-Weber Syndrome

Klippel-Trenaunay-Weber syndrome (KTWS) is a congenital malformation syndrome involving blood and lymph vessels and disturbed bone and soft tissue growth. Complications of KTWS include deep-vein thrombosis, pulmonary embolism, gastrointestinal bleeding, and vascular (usually lymphatic) blebs within capillary malformations. We present a case of a young male patient with KTWS who presented with superficial venous thrombosis and microangiopathic hemolytic anemia in a presentation similar to disseminated intravascular coagulation. He was ultimately maintained on prophylactic rivaroxaban to prevent recurrent thrombotic events. We performed a literature search to identify similar cases and to summarize common presenting features and treatment modalities that were offered.
 Résumé
 Le syndrome de Klippel-Trenaunay-Weber (KTWS) est un syndrome de malformation congénitale impliquant le sang et les vaisseaux lymphatiques et les os perturbés et la croissance des tissus mous. Les complications de la KTWS comprennent la thrombose veineuse profonde, l'embolie pulmonaire, les saignements gastro-intestinaux et les bulles vasculaires (habituellement lymphatiques) dans les malformations capillaires. Nous présentons un cas d'un jeune patient mâle avec KTWS qui a présenté une thrombose veineuse superficielle et une anémie hémolytique microangiopathique dans une présentation semblable à la coagulation intravasculaire disséminée. Il a finalement été maintenu sur des rivaroxaban prophylactiques pour prévenir les épisodes récurrents de purpura. Nous avons effectué une recherche documentaire pour identifier des cas similaires et pour résumer les caractéristiques communes de présentation et les modalités de traitement qui ont été offerts.
 
 

Plasma levels of vitamin K and the risk of ischemic heart disease: a Mendelian randomization study

Essentials Vitamin K plays a role in coagulation, and deficiency may promote coronary artery calcification. The role of vitamin K1 in heart disease was assessed using Mendelian randomization in Caucasians. Genetically higher vitamin K1 was associated with a higher risk of ischemic heart disease. Further research elucidating the role of vitamin K1 in ischemic heart disease could be useful. Background Vitamin K1 is a nutrient in green leafy vegetables; deficiency may promote coronary artery calcification. Warfarin, an anticoagulant used in secondary prevention of thrombotic events, is a vitamin K antagonist. Thrombotic and coronary events may share risk factors. Objectives To clarify the role of vitamin K1 in ischemic heart disease, the risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically determined vitamin K1 levels. Given vitamin K1 is fat soluble, associations with lipids were similarly assessed to assess pleotropic effects via lipids. Methods Separate sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used to obtain an unconfounded estimate of the association of vitamin K1 (based on rs2108622 [CYP4F2], rs4645543 [KCNK9] and rs2192574 [CTNNA2] from a genome-wide association study) with CAD/MI using CARDIoGRAMplusC4D (cases = 64 374; controls = 130 681) and with lipids using Global Lipids Genetics Consortium Results (n = 196 475). Results Vitamin K1 single nucleotide polymorphisms were positively associated with CAD/MI (odds ratio [OR], 1.17 per unit [nmol L(-1) ] of natural log-transformed genetically predicted vitamin K1 ; 95% confidence interval [CI], 1.08-1.26), but not with inverse normal transformed low-density lipoprotein cholesterol (-0.0003; 95% CI, -0.03 to 0.03), high-density lipoprotein cholesterol (0.02; 95% CI, -0.01 to 0.05) or triglycerides (-0.01; 95% CI, -0.04 to 0.02). Considering only rs2108622, which is functionally relevant to vitamin K1 , the association for CAD/MI was stronger (OR, 1.21; 95% CI, 1.08-1.36). Conclusions Vitamin K may cause CAD/MI; whether vitamin K or other determinants of coagulation could be relevant to primary prevention might be worth considering.

MULTIGENIC THROMBOPHILIAAS A RISK FACTOR OF RECURRENT STROKE

Thrombosis significantly impact on the overall morbidity and mortality in all age groups. The cause of stroke remains unknown in approximately 20% of cases. The article presents a brief review of the most common hereditary and acquired thrombophilia. One of the methods of etiologic diagnostic of thrombophilia is revealing the markers of hereditary or acquired diseases with molecular and genetic typing of haemostatic system factors. We present a case report of recurrent cerebral thrombosis in both vascular regions of the brain due to multigenic thrombophilia. The final objective of the research is not only to reveal the possible causes and risk factors of thrombosis but also to implement effective secondary prevention of thrombotic events.

Aspirin in the perioperative period: a review of the recent literature.

The indications for aspirin (ASA) for both primary and secondary prevention of thrombotic events continue to evolve. We review some of these indications and the recent literature regarding the perioperative administration of ASA. ASA for primary prevention of cardiac ischemia, stroke, cancer, and death remains controversial. When used for primary prevention, ASA may be safely discontinued perioperatively. Patients with coronary or carotid artery stents should continue to receive ASA perioperatively. For patients with ischemic heart disease currently receiving ASA for secondary prevention of cardiac ischemia and stroke undergoing general surgery, orthopedic surgery, ophthalmological surgery, cardiovascular surgery, major vascular surgery, or a urological procedure, continuation of ASA is probably well tolerated, but further study is required. There is no indication to initiate ASA perioperatively in patients with stable ischemic heart disease as the risks outweigh the benefits. Until further data become available, decisions regarding the perioperative continuation of ASA should be made on a case-by-case risk-benefit analysis. The continuation or discontinuation of ASA perioperatively remains a complicated issue. Further, well designed trials are needed for additional clarification.

MO2 - A Comparison Of State Transition And Discrete Event Modeling Approaches For Antiplatelet Use In The Secondary Prevention Of Thrombotic Events After Myocardial Infarction (MI)

MO2 - A Comparison Of State Transition And Discrete Event Modeling Approaches For Antiplatelet Use In The Secondary Prevention Of Thrombotic Events After Myocardial Infarction (MI)

Role of Antiplatelet Therapies in Preventing Atherothrombosis

Platelets exhibit a major role in development and progression of atherothrombosis. The normal function of platelets is to secure hemostasis at sites of vascular injuries. Abnormal endovascular structure may result in excessive platelet function with consequence of progressive or acute reduction in vascular lumen and cessation of blood flow. Despite succeeding in averting bleeding, total occlusion of a vessel leads to inevitable ischemia with eventual cell death upon lack of blood supply clinically manifesting as myocardial infarction in coronary vessels, cerebral infarction (stroke) in cerebral vessels, or peripheral gangrene in peripheral arterial disease. Antiplatelets long have been used to halt the process of atherothrombosis preventing further tissue damage at the expense of bleeding as well as other side effects. In this review, the role of antiplatelets in primary and secondary prevention of thrombotic events is explored in light of evidence based clinical practice.

Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial

Vorapaxar inhibits platelet activation by antagonising thrombin-mediated activation of the protease-activated receptor 1 on human platelets. The effect of adding other antiplatelet drugs to aspirin for long-term secondary prevention of thrombotic events in stable patients with previous myocardial infarction is uncertain. We tested this effect in a subgroup of patients from the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial. In TRA 2°P-TIMI 50--a randomised, placebo-controlled, parallel trial--we randomly assigned patients with a history of atherothrombosis to receive vorapaxar (2·5 mg daily) or matching placebo in a 1:1 ratio. Patients, and those giving treatment, assessing outcomes, and analysing results were masked to treatment allocation. Patients with a qualifying myocardial infarction within the previous 2 weeks to 12 months were analysed as a pre-defined subgroup. The primary efficacy endpoint was cardiovascular death, myocardial infarction, or stroke, analysed by intention to treat. We analysed events by Kaplan-Meier analysis and compared groups with a Cox proportional hazard model. TRA 2°P-TIMI 50 is registered at ClinicalTrials.gov (NCT00526474). 17,779 of 26,449 patients had a qualifying myocardial infarction and were assigned treatment (8898 to vorapaxar and 8881 to placebo). Median follow-up was 2·5 years (IQR 2·0-2·9). Cardiovascular death, myocardial infarction, or stroke occurred in 610 of 8898 patients in the vorapaxar group and 750 of 8881 in the placebo group (3-year Kaplan-Meier estimates 8·1%vs 9·7%, HR 0·80, 95% CI 0·72-0·89; p<0·0001). Moderate or severe bleeding was more common in the vorapaxar group versus the placebo group (241/8880 [3·4%, 3-year Kaplan-Meier estimate] vs 151/8849 [2·1%, 3-year Kaplan-Meier estimate], HR 1·61, 95% CI 1·31-1·97; p<0·0001). Intracranial haemorrhage occurred in 43 of 8880 patients (0·6%, 3-year Kaplan-Meier estimate) with vorapaxar versus 28 of 8849 (0·4%, 3-year Kaplan-Meier estimate) with placebo (p=0·076). Other serious adverse events were equally distributed between groups. For patients with a history of myocardial infarction, inhibition of protease-activated receptor 1 with vorapaxar reduces the risk of cardiovascular death or ischaemic events when added to standard antiplatelet treatment, including aspirin, and increases the risk of moderate or severe bleeding. Merck.

Antiplatelet drug response variability and the role of platelet function testing: A practical guide for interventional cardiologists

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndrome and is also of particular importance in those who undergo percutaneous coronary intervention with stent implantation. Dual antiplatelet therapy with aspirin and clopidogrel is associated with improvement in long-term clinical outcomes in such patients and is presently the antiplatelet therapy of choice for secondary prevention of thrombotic events. However, a significant number of patients experience recurrent events despite antiplatelet therapy. Although poor patient compliance can account for some of these events, particularly in those patients who receive a drug-eluting stent, increasing evidence indicates that there is variability in response to antiplatelet therapy and patients who have higher levels of platelet reactivity are at increased risk for recurrent ischemic events. However, the lack of a consistent definition of inadequate platelet response, as well as the lack of a standardized measurement technique, has made it difficult to define how to treat these patients. To translate findings associated with variability in platelet response into improved patient care, it is necessary to gain a better understanding of what variable platelet response is, how it is measured, who it should be measured in, and what its clinical relevance is. The objective of this review is to evaluate the data regarding interindividual response variability to antiplatelet therapy with the aim of providing practical considerations and where possible, recommendations, regarding this topic for interventional cardiologists.

The Thromboxane A 2 Receptor Antagonist S18886 Prevents Enhanced Atherogenesis Caused by Diabetes Mellitus

S18886 is an orally active thromboxane A2 (TXA2) receptor (TP) antagonist in clinical development for use in secondary prevention of thrombotic events in cardiovascular disease. We previously showed that S18886 inhibits atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice by a mechanism independent of platelet-derived TXA2. Atherosclerosis is accelerated by diabetes and is associated with increased TXA(2) and other eicosanoids that stimulate TP. The purpose of this study was to determine whether S18886 lessens the enhanced atherogenesis in diabetic apoE(-/-) mice. Diabetes mellitus was induced in apoE(-/-) mice with streptozotocin and was treated or not with S18886 (5 mg.kg(-1).d(-1)). After 6 weeks, aortic lesion area was increased >4-fold by diabetes in apoE(-/-) mice, associated with similar increases in serum glucose and cholesterol. S18886 largely prevented the diabetes-related increase in lesion area without affecting the hyperglycemia or hypercholesterolemia. S18886 prevented deterioration of endothelial function and endothelial nitric oxide synthase expression, as well as increases in intimal markers of inflammation associated with diabetes. In human aortic endothelial cells in culture, S18886 also prevented the induction of vascular cell adhesion molecule-1 and prevented the decrease in endothelial nitric oxide synthase expression caused by high glucose. The TP antagonist inhibits inflammation and accelerated atherogenesis caused by diabetes, most likely by counteracting effects on endothelial function and adhesion molecule expression of eicosanoids stimulated by the diabetic milieu.