Antithrombotic therapy in heparin-induced thrombocytopenia: guidelines translated for the clinician

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome initiated by heparin exposure and characterized by thrombocytopenia and paradoxical thrombophilia. HIT is mediated by the formation of antibodies against the platelet factor 4/heparin complex, which leads to platelet activation, thrombin generation, and potentially fatal thrombotic sequelae. The clinical presentation of HIT is variable and can be easily overlooked. Although a number of functional and antigen-based immunoassays have been developed to detect the presence of HIT antibodies, initial diagnosis is often based on recognition of thrombocytopenia in the appropriate clinical context and later confirmed with immunologic testing. Given the serious clinical consequences of HIT, immediate cessation of heparin products and administration of non-heparin anticoagulants are crucial components of treatment. We provide a review of the clinical syndrome and practical summary of treatment recommendations from the most recent 2012 American College of Chest Physicians evidence-based guidelines for the treatment and prevention of HIT.     

Antithrombotic therapy in atrial fibrillation: guidelines translated for the clinician

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, accounting for approximately one-third of hospitalizations for cardiac rhythm disturbances. The highest incidence of AF is in patients 70-80 years old and other high-risk populations. Although the diagnosis of AF is usually straightforward, effective treatment strategies are less well implemented. This is particularly true for antithrombotic therapy, which is very effective at preventing thromboembolic complications of AF. Stroke is the most significant morbidity in AF patients. The yearly risk of stroke increases from 1.5% for AF patients aged 50-59 to 23% for those aged 80-89. Ischemic strokes secondary to AF carry twice the risk of death when compared with strokes from other causes. We provide a practical and useful review of the most recent American College of Cardiology/American Heart Association/European Society of Cardiology guidelines-based care and future directions of antithrombotic therapy for patients with AF.     

Antithrombotic therapy in acute coronary syndromes: guidelines translated for the clinician

The use of anticoagulant and antiplatelet therapy during the management of acute coronary syndromes (ACS) has been associated with improvements in short- and long-term clinical outcomes, regardless of whether patients are managed conservatively or with acute coronary revascularization. Translating the existing evidence for selection of the most appropriate antithrombotic strategy has been summarized in available guideline recommendations. Given the breadth of antithrombotic recommendations across existing U.S. and European guidelines, synthesis of these recommendations for practicing clinicians who treat patients with ACS are increasingly desired. Providing a summary of the similarities across guidelines while noting the areas where divergence exists becomes an important facet in translating optimal antithrombotic management in ACS for the treating clinician. This review highlights the important aspects of clinical practice guidelines that practicing physicians should consider when selecting antithrombotic therapies to reduce ischemic risk while minimizing hemorrhagic risk across all ACS subtypes.     

Antithrombotic therapy for ischemic stroke: guidelines translated for the clinician

Acute ischemic stroke is the result of abrupt interruption of focal cerebral blood flow. The majority of ischemic strokes are caused by embolic or thrombotic arterial occlusions. Acute stroke management is complex, in part because of the varying etiologies of stroke and the very brief window of time for reperfusion therapy. Efforts to optimize stroke care have also encountered barriers including low public awareness of stroke symptoms. As initiatives move forward to improve stroke care worldwide, health care providers and institutions are being called onto deliver the most current evidence-based care. Updated versions of three major guidelines were published in 2008 by the American College of Chest Physicians, the American Heart Association, and the European Stroke Organization. This article presents a concise overview of current recommendations for the use of fibrinolytic therapy for acute ischemic stroke and antithrombotic therapy for secondary prevention. Future directions are also reviewed, with particular emphasis on improving therapeutic options early after stroke onset.     

Antithrombotic therapy in TAVI

Transcatheter aortic valve implantation (TAVI) carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials (RCT) were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3?6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3?12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.     

Antithrombotic therapy in atrial fibrillation

Atrial fibrillation is a common condition affecting elderly individuals; as many as 10% of people older than age 80 years have AF. AF is also a potent risk factor for ischemic stroke, raising the risk of stroke fivefold. A set of consistent randomized controlled trials has demonstrated that long-term anticoagulation can largely reverse the risk of stroke attributable to AF. In these trials, anticoagulation generally proved quite safe, raising the risk of intracranial hemorrhage by less than 0.5% per year. The anticoagulation target for AF is INR 2 to 3 with INR 2.5 as the specific goal. The trials were much less consistent about the efficacy of aspirin, although it seems that aspirin has a small stroke-preventive effect. The recommended dose of aspirin is 325 mg per day. Because it raises the risk of hemorrhage and adds the burden of frequent monitoring of INR values, anticoagulation is recommended for those patients with AF at higher risk of stroke. Such higher risk is conferred by the following risk factors: (1) a history of a prior stroke, TIA, or other systemic embolic event; (2) a history of hypertension; (3) diabetes mellitus; (4) left ventricular dysfunction; (5) mitral stenosis; and (6) older age. The exact age threshold conferring sufficiently increased risk is uncertain, with some research indicating the threshold should be age 65 years, and other research indicating the threshold should be age 75 years. For lower-risk patients, aspirin is recommended. Future research should focus on the oldest patients with AF. These individuals face the highest risk of ischemic stroke without anticoagulation and the highest risk of major hemorrhage with anticoagulation. Only small numbers of such elderly patients were included in the randomized trials. Future research should also focus on improved risk stratification, allowing better targeting of anticoagulation. Discoveries of new antithrombotic agents and new drugs and devices for preservation of sinus rhythm could radically improve stroke-preventive strategies for AF.     

Antithrombotic therapy in the elderly

Antithrombotic therapy represents the mainstay of treatment for prevention of recurrent ischemic events in patients with atherothrombotic disease processes. Although the benefits of antithrombotic pharmacotherapy in the elderly are well established, the elderly are generally more vulnerable to the adverse effects of antithrombotic drugs. Such higher vulnerability may be related to distinct pharmacokinetic and pharmacodynamic responses in the late age of life, during which drug-drug interactions due to polypharmacy further enhance the risk of adverse effects associated with the use of antithrombotic agents. Given that the prevalence of atherothrombotic disease, as well as diseases with thromboembolic potential, increases exponentially with age and that the elderly population is in continuous growth, understanding strategies of antithrombotic management in these patients is of key importance. The present paper provides an overview of the current available evidence on the use of antithrombotic therapy in elderly patients with the primary focus on treatment of coronary artery disease.     

Antithrombotic therapy in cerebrovascular disease

For more than two decades, anticoagulant and antiplatelet agents have been used routinely to prevent and treat ischemic stroke. Although recent clinical trials have shown that such treatment can be helpful in certain cases, antithrombotic therapy currently remains of unproven benefit in many clinical settings of cerebrovascular disease. Although the absence of data confirming clinical efficacy has generated uncertainty and hesitancy in some clinicians, the lingering conviction that antithrombotic therapy is efficacious has led others to continue a policy of routine and active therapeutic intervention. A critical analysis of the literature on antithrombotic therapy and cerebrovascular disease suggests that many acceptable management options lie between the extremes of therapeutic nihilism and "routine" intervention.     

Antithrombotic strategies in gene therapy

Advances in the field of molecular medicine are making gene therapy a viable treatment strategy for the next millennium. Indeed, over the past 10 years, a number of improvements have occurred that have resulted in an increased interest in gene therapy for the treatment of diseases in cardiovascular medicine. Because antithrombotic and anticoagulation therapy generally involves the systemic administration of agents that target a small region of the vasculature, localized and controlled delivery of specific genes could offer enormous potential to treat a number of life-threatening diseases. In addition, gene therapy may allow sustained antithrombotic or anticoagulant treatment when prolonged systemic administration is undesirable. Gene therapy for antithrombotic strategies can involve a number of different approaches. This could include inhibition of coagulation factors, over-expression of anticoagulant factors, o modulation of endothelial biology to make thrombus formation or propagation unfavorable. Preclinical data regarding these different strategies are reviewed and their potential limitations discussed.     

Antithrombotic therapy in cardiac embolism

Anticoagulation is indicated in most cardioembolic ischemic strokes for secondary prevention. In many cardiac conditions, anticoagulation is also indication for primary stroke prevention, mainly when associated to vascular risk factors. Anticoagulation should be started as soon as possible, as it is safe even in moderate acute strokes. The efficacy of early anticoagulation after cardioembolic stroke in relation to outcome has not been assessed adequately, but there is evidence from animal models and clinical studies that anticoagulation with unfractionated heparin is associated with a better outcome mediated in part by its anti-inflammatory properties.     

Antithrombotic therapy in atrial fibrillation

Warfarin is highly effective at reducing the risk of stroke in atrial fibrillation. The benefit of oral anticoagulant therapy strongly outweighs the risk in most patients with atrial fibrillation. More data are needed to define better the overall risk-to-benefit ratio for patients age 80 years and greater. Because a significant proportion of elderly individuals may not be optimal candidates for anticoagulant therapy, alternative stroke prevention strategies must continue to be evaluated while redoubling efforts to understand the mechanisms underlying atrial fibrillation and thrombogenesis.     

Antithrombotic therapy in historical perspective

The history of antithrombotic therapy is traced over the past 5 decades, with a focus on the treatment of 2 major disorders: venous thromboembolism and acute myocardial infarction. Five subjects pertinent to clinical management decisions are discussed: (1) theories of thrombosis and coagulation, (2) tests of coagulation, (3) the availability of therapeutic interventions, (4) techniques for the diagnosis of vascular obstruction, and (5) the use and misuse of clinical trials.     

他汀类药物调脂治疗

他汀类药物即 3羟基 3甲基戊二酰辅酶A(3-hydroxy- 3-methylglutaryl-coenzymeA ,HMG CoA)还原酶抑制剂 (由于这类药物的英文名称词尾均为statin ,统称为statins,即他汀类 ) ,具有竞争性抑制细胞内胆固醇合成早期过程中限速酶的活性 ,继而上调细胞表面低密度脂蛋白(LDL)受体 ,加速血浆LDL的分解代谢 ,此外还可抑制极低密度脂蛋白 (VLDL)的合成。由于他汀类药物能有效地降低LDL -胆固醇 (LDL C)和总胆固醇 (TC)水平 ,具有良好的耐受性和安全性 ,因而已成为治疗高胆固醇血症最常用的药物。所以 ,他汀类药物的发现 ,给高胆固醇血症…     

Antithrombotic therapy in valvular heart disease

Whether antithrombotic therapy in elderly patients differs from that in younger populations depends on whether the risk for such bleeding differs in the elderly. Regarding long-term therapy with warfarin derivatives, evidence shows that there is a difference. The anticoagulation response to warfarin is exaggerated with advancing age. This article discusses antithrombotic therapies for valvular heart disease, including bioprosthetic and mechanical prosthetic heart valves, aspirin and dipyridamole in combination with oral anticoagulant therapy, antiplatelet agents alone or in combination with very low dose warfarin, tilting disk valves, valve position, first-generation valves compared with modern valves, interruption of anticoagulant therapy, and miscellaneous indications for antithrombotic therapy.