Compliance and adherence to oral anticoagulation therapy in elderly patients with atrial fibrillation in the era of direct oral anticoagulants

Elderly patients with atrial fibrillation usually have more concomitant conditions that affect compliance and adherence to anticoagulant therapy. Direct oral anticoagulants seem to be associated with better adherence; however, there is still room to improve continuous coagulation control and adherence among elderly patients receiving anticoagulants in everyday practice.     

Gouty tophi in the bone marrow

Heparin induced thrombocytopenia (HIT) remains a rare, but significant, condition related to mortality and morbidity. The incidence has decreased with reduced use of unfractionated heparin, with the exception of cardiac surgery. Due to the high risk of thrombosis, a switch to a non‐heparin anticoagulant is required, until platelet counts normalize. Within the acute setting, argatroban, fondaparinux and direct acting oral anticoagulants (DOACS) are therapeutic options. In patients with HIT‐associated thrombosis or who require long‐term anticoagulation, warfarin remains the preference, but DOACs are attractive alternatives.     

The evolution of anticoagulant therapy

Arterial and venous thromboembolism are leading causes of morbidity and mortality around the world. For almost 70 years, heparins (unfractionated heparin and low molecular weight heparins) and vitamin K antagonists have been the leading therapeutic medical options for the treatment and prevention of thromboembolic disorders. Nevertheless, the many limitations of these traditional anticoagulants have fuelled the search for novel agents over the past 15 years, and a new class of oral anticoagulants that specifically target activated factor X and thrombin has been developed and is now commercially available. In this narrative review, the evolution of anticoagulant therapy is summarised, with a focus on newer oral anticoagulants.     

Antithrombotic therapy during percutaneous coronary intervention

Ischemic complications of percutaneous coronary intervention occur commonly and are among the major limitations of the procedure. Both platelets and thrombin play an essential role in the response to the arterial injury that follows coronary intervention and in the pathophysiology of the ischemic complications of the procedure. Aspirin and heparin are essential treatments for the patient undergoing coronary intervention. Novel thrombin and platelet inhibitors are being developed that may be useful for improving both acute and long-term clinical outcomes of percutaneous coronary intervention.     

肿瘤合并心房颤动的卒中风险评估及抗凝治疗

肿瘤患者中的心房颤动发病率高于一般人群,肿瘤合并心房颤动时卒中风险亦明显增加,而目前指南并未明确该类患者的卒中及其抗凝相关出血风险的评估,临床仍沿用心房颤动的评估量表,忽略了肿瘤及其治疗等因素而低估了风险。此外,传统抗凝药物因其药物相互作用等原因在肿瘤合并心房颤动患者中应用受限,而新型口服抗凝药物的有效性和安全性相关研究得到了广泛关注。     

Stroke Prevention in Atrial Fibrillation: Concepts and Controversies

Atrial fibrillation (AF) is the commonest cardiac rhythm disorder worldwide, affecting 1% of the general population. It is estimated that up to 16 million people in the US will suffer from the arrhythmia by 2050. AF is an independent stroke risk factor and associated with more severe strokes. For six decades, warfarin has been the only truly effective therapy to protect against stroke for patients with atrial fibrillation. Despite the proven worth of warfarin, its limitations have seen reluctance amongst physicians and patients to utilise this efficacious agent. This has meant that substantial numbers of patients are either unprotected against stroke or suboptimally protected with antiplatelet therapy.Contemporary well-validated stroke risk factor schemes (CHA₂DS₂-VASc) now permit rapid but comprehensive evaluation of a patient’s risk for thromboembolism, allowing better identification of low-risk patients who do not require antithrombotic therapy, and whilst for those with ≥1 stroke risk factors require formal oral anticoagulation. Aspirin has been proven to be inferior to anticoagulation, and is not free of bleeding risk. We also have simple scores to easily evaluate a patient’s risk of haemorrhage (e.g. HAS-BLED).The emergence of new oral anticoagulants should further improve stroke prevention in AF, and they successfully negotiate many of the hurdles to oral anticoagulation generated by warfarin’s limitations. Monitoring, reversal, and perioperative management are areas which require further investigation to enhance our ability to safely and effectively utilise the new agents.     

Antithrombotic Therapy in Nonvalvular Atrial Fibrillation: Consensus and Challenges

Atrial fibrillation (AF) is associated with high risk of systemic thromboembolism leading to significant morbidity and mortality. Warfarin, previously the mainstay for stroke prevention in AF, requires close monitoring because of multiple food and drug interactions. In recent years, food and drug administration has approved several direct oral anticoagulants (DOACs) for use in patients with nonvalvular AF. These agents have not been studied in patients with valvular AF who are at an even higher risk of systemic thromboembolism. DOACs do not require frequent blood testing or changes in dosage except when renal function deteriorates, however, the lack of established antidotes for many of these agents remains a challenge. Also, currently there is no head-to-head comparison between these agents to guide clinical choice. This article discusses the advantages and disadvantages of currently approved oral antithrombotics in nonvalvular AF, with a special emphasis on the DOACs and their individual characteristics.     

The Impact of Heparin Compounds on Cellular Inflammatory Responses: A Construct for Future Investigation and Pharmaceutical Development

Atherosclerotic disease is recognized as a chronic inflammatory disorder with intermittent and widely variable phases of cellular proliferation and heightened thrombotic activity. The multi-tiered links between inflammation, atherogenesis and thrombogenesis provide a unique opportunity for research and development of pharmaceuticals which target one or more critical pathobiologic steps (Fig. 1).The purpose of the following review on heparin compounds is to comprehensively examine the multi-cellular, pleuripotential effects of a commonly used anticoagulant drug in the context of normal and disease-altered vascular responses and illustrate possible constructs for avenues of subsequent investigation in the field of atherothrombosis.The overview is divided into five integrated parts; antiinflammatory properties of the normal vessel wall, the relationship between glycosaminoglycans and inflammation, heparin-mediated effects on cellular inflammatory responses, association between molecular weight and antiinflammatory capabilities, and oral heparin compounds for achieving prolonged cell-based inhibition.     

Antithrombotic therapy in cardiac stent patients

The use of coronary stents has made a significant impact on immediate angiographic results of coronary angioplasty as well as on the more important incidence of restenosis and the need for repeat procedures. This could not have been accomplished without adjuvant antithrombotic therapy directed predominantly at platelet function. Antiplatelet agents have significantly reduced the complications and improved the long-term outcome following coronary stent placement. This paper reviews the evolution of adjuvant antithrombotic therapy following stent placement, the agents currently used and future directions being investigated.     

Antithrombotic therapy for the treatment of atrial fibrillation in the elderly

Atrial fibrillation significantly raises the risk for ischemic stroke, and the prevalence of atrial fibrillation is increasing due to the aging of the population. Reducing the risk of ischemic stroke is one of the cornerstones in the medical management of atrial fibrillation. Oral vitamin K antagonists such as warfarin are highly effective in preventing atrial fibrillation-related thromboembolism, but can be challenging to manage and are associated with increased bleeding risk. Aspirin therapy has modest efficacy in reducing stroke risk, but is much less effective than warfarin. To help guide the choice of optimal antithrombotic therapy, risk stratification for stroke in atrial fibrillation may be helpful, although most elderly patients derive a net benefit from warfarin. Older patients have higher bleeding rates on warfarin and are at higher risk for intracranial hemorrhage. Although the risk of intracranial hemorrhage is generally quite low, its occurrence is associated with significant mortality and disability, and more effective methods to risk stratify patients for intracranial hemorrhage are needed.     

Antithrombotic therapy for patients with cardiac disease

The use and type of antithrombotic therapy for patients with cardiac disease are described based on an understanding of the pathophysiologic mechanisms involved, the risk of thromboembolism, and the evidence from prospective and, if necessary, retrospective clinical trials. The indications and intensity of anticoagulant therapy in patients with valvular heart disease and prosthetic valves are first discussed. We recommend that the prothrombin time be reported as a ratio and standardized using the International Normalized Ratio. The pivotal role of platelets and the clotting system in the initiation and progression of atherosclerosis and the acute coronary syndromes is described. There is no evidence to date that antiplatelet therapy is of value in primary prevention or in patients with stable angina, but the value of aspirin in patients with unstable angina was clearly shown in two well-designed studies. Adequate prophylactic therapy to prevent the thrombotic complications of acute myocardial infarction (i.e., venous thrombosis and intracardiac thrombosis) is described, and the available data on the prevention of coronary reocclusion after thrombolysis reviewed. There is now convincing evidence from studies in animals and in patients that vascular injury during aortocoronary vein bypass graft surgery requires antitihrombotic therapy starting before the procedure to minimize acute platelet thrombus deposition and prevent occlusion. Restenosis after arterial angioplasty appears to be related to acute platelet thrombus deposition on the site of deep arterial injury. Therapeutic interventions should probably involve both anticoagulants and platelet inhibitor therapy. Implications derived from recent animal studies are discussed.     

A New Option for Reversing the Anticoagulant Effect of Factor Xa Inhibitors: Andexanet Alfa (ANDEXXA)

The use of direct oral anticoagulants over traditional warfarin has increased in the United States over the past 10 years because of advantages such as ease of use, predictable pharmacokinetic response, and safety. In 2015, the U.S. Food and Drug Administration approved idarucizumab (Praxbind) for the reversal of the direct thrombin inhibitor dabigatran, but no reversal agent has been available for oral factor Xa (FXa) inhibitors until recently. Andexanet alfa was approved in May 2018, under the brand name ANDEXXA, for the reversal of 2 of FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs. This accelerated approval was based on change in anti-FXa activity from baseline that indicated a reversal of the anticoagulant effect. Any expanded Food and Drug Administration indication will be contingent on results demonstrating improved hemostasis and efficacy for reversing other FXa inhibitors.