Present and future of antithrombotic therapy in acute coronary syndromes

Antithrombotic therapy in the management of an acute coronary syndrome is designed to inhibit both the coagulation cascade and platelet activation, thus preventing the development of the pathophysiological consequences of these processes. The main therapeutic approaches used for this purpose are unfractionated heparin, low-molecular-weight heparins, or direct antithrombins, all of them being molecules that interfere with the formation of a thrombin clot. Numerous clinical studies have investigated the advantages and disadvantages of each of these strategies and the benefits and risks of combined therapy with these drugs or their association with platelet inhibitors. The difficulty of establishing the relative benefits of different therapeutic approaches is due in part to the enormous number of possible combinations and the different clinical situations in which they can be used. In addition, the need for antithrombotic agents with a more specific inhibitor activity and a broader therapeutic range is motivating active investigation in laboratories worldwide. This has lead to the design of recombinant molecules and monoclonal antibodies that interrupt the activation of the coagulation cascade in several strategically important points. The relation between the clinical benefits obtained from this new generation of molecules and the increased health care costs generated by their design and development remains to be seen.     

The future prospects of antithrombotic therapy in peripheral vasculopathy

Peripheral vascular disease is characterized by progressive atherosclerotic deterioration of peripheral arteries and coronary and cerebral vascular complications. Antiplatelet treatment retards the progression of peripheral atherosclerosis but it is still unclear if this is associated with a reduced risk of amputation. Vasodilator prostaglandins have been administered in critical ischemia but the results have been disappointing. An alternative approach to enhance peripheral vasodilation is to increase nitric oxide production, which is reduced in peripheral vascular disease, particularly in the case of severe ischemia. Critical ischemia secondary to thromboembolism has been treated with thrombolysis within 7 days of the acute episode, but this approach is no more effective than vascular surgery in reducing amputation; earlier treatment should be planned to further investigate its clinical efficacy. The effect of antiplatelet treatment in preventing cardiovascular events was investigated in three randomized trials with negative results. A post-hoc analysis of the CAPRIE study demonstrated that clopidogrel is superior to aspirin in preventing cardiovascular disease. This suggests that antiplatelet treatment may be efficacious in this setting; future study should assess if its combination with other drugs, such as statins, that retard coronary atherosclerotic progression, could further reduce cardiovascular complications in peripheral vascular disease.     

Oral antithrombotic therapy and one-year clinical outcomes among patients with atrial fibrillation in resource-limited settings

BackgroundAtrial fibrillation is associated with increased risk of morbidity and mortality. There's limited data on the outcomes of atrial fibrillation patients in Africa. We aimed at evaluating the clinical outcomes and their associated factors in patients with atrial fibrillation on antithrombotic therapy in Douala.MethodsThe Douala atrial fibrillation registry is a prospective, observational cohort study of patients with atrial fibrillation followed by cardiovascular specialists in 3 specialized care centres. From January to April 2018, all patients with electrocardiographic diagnosis of atrial fibrillation, aged 21 years or older, were included in the registry provided their consent. The composite endpoint of heart failure, stroke, major bleeding, hospitalisation and mortality as well as their individual occurrence were assessed at 12 months.ResultsOf 113 participants that were included, 6(5.3%) were lost to follow-up. The mean age was 70 ± 12 years, with a female predominance (68%). After a mean follow-up time of 12.2 ± 0.7 months, 51 patients (47.7%) had at least one outcome. Hospitalisation, all-cause mortality, heart failure, stroke and major bleeding rates were 33.3%, 16.8%, 15.2%, 4.8% and 2.9% respectively. There was no significant difference in the composite outcome and mortality according to the antithrombotic treatment. Previous heart failure [aHR = 3.07, 95% CI (1.48–6.36) p = 0.003], new onset atrial fibrillation [aHR= 4.00, 95% CI (0.96–8.19) p < 0.001] and paroxystic atrial fibrillation [aHR= 3.74, 95% CI (1.33–10.53) p = 0.013] were significant predictors of outcome.ConclusionHalf of patients with atrial fibrillation in this registry developed an outcome after one year of follow-up, with heart failure, new onset and paroxystic atrial fibrillation being the main predicting factors. Diagnosing and managing atrial fibrillation in patients with heart disease should therefore be considered as a key priority.     

Perioperative management of antithrombotic therapy

The management of patients who require temporary interruption of warfarin therapy because of elective surgery or another invasive procedures is clinically important because of the increasing prevalence of patients who are receiving warfarin and the availability of low-molecular-weight heparins, which facilitate out-of-hospital perioperative anticoagulation. The two main issues that need to be considered in perioperative anticoagulant management is the patient's risk of a thromboembolic event when warfarin therapy is interrupted and the risk of bleeding that is associated with the surgery or procedure. An assessment of these factors will determine the optimal perioperative anticoagulant management approach. The overall objective of this review is to provide a practical approach relating to perioperative anticoagulation which can be used in everyday clinical practice.     

Fundamentals of antithrombotic therapy]

The physiological and biochemical reactions leading to intravascular clot formation are reported on as far as their representation is required for an understanindg of the pathogenesis of thrombosis and its pharmacological control.     

Perioperative management and reversal of antithrombotic therapy

Patients of advanced age commonly undergo invasive procedures and surgery. With the number of elderly individuals being treated with long-term anticoagulant therapy growing annually, it is not uncommon that surgery is contemplated for older adults on long-term anticoagulant therapy. This article focuses on the management of elderly patients who are on long-term anticoagulant therapy, principally with warfarin, who must undergo invasive procedures. Although no consensus has been reached regarding the perioperative management of patients on long-term anticoagulation therapy, this discussion presents the current status and some recommendations for practice.     

Pharmacogenetics in cardiovascular antithrombotic therapy

Thrombosis is the most important underlying mechanism of coronary heart disease and embolic stroke. Therefore, antithrombotic therapy is commonly used in cardiovascular diseases. Unfortunately, the benefits are limited, and an important proportion of treated patients will suffer a new thrombotic event. Lack of clinical benefits may be related to heterogeneous response to antithrombotic treatment among individuals (inter-individual heterogeneity). Few factors have been identified to be involved in this inter-individual heterogeneity. Recently, pharmacogenetic has emerged as a new field in medicine that tries to identify gene variants able to explain the heterogeneity in patient's response to a drug. Polymorphisms affecting disposition, metabolism, transporters or targets of the drug could modify the individual response to one therapy, and probably its side effects. The present review article explores the genetic influence on antithrombotic drug efficacy, analysing the modulating role of different polymorphisms on individuals' response to drugs commonly used in current day practice.     

The use of antithrombotic therapy in the elderly

The elderly are predisposed to atherosclerosis and venous thrombosis, the conditions for which anticoagulants are used. Anticoagulants can be used safely in the elderly with little or no more risk of bleeding than exists in younger patients. The prescribing physician must know the mechanism of drug action, be attentive to potential side effects, and monitor drug activity adequately. The authors emphasize the oral anticoagulants and heparin because, in general, their use is associated with a greater degree of risk and more clearly defined benefits than would apply for the antiplatelet agents.     

Antiplatelet and antithrombotic therapy in unstable angina

In 4 well-controlled clinical trials, aspirin reduced the incidence of coronary events in unstable angina. The benefits were present during the acute, subacute and more chronic phases of the disease and were independent of the doses and of other protocol differences. This benefit of aspirin can be extended to some, but not all, other antiplatelet drugs. In 4 clinical trials, heparin used acutely added substantial benefit to the management of unstable angina, reducing the event rate and also the incidence of refractory angina more than aspirin. The long-term benefit of antithrombin therapy remains to be more thoroughly investigated. Despite these successes, the failure rate of aspirin and of heparin remains high, justifying a continuing search for more potent and safe antiplatelet and antithrombotic drugs.     

围手术期的抗栓治疗——ACCP9溶栓和抗栓指南启示

随着社会人口老龄化,慢性房颤、深静脉血栓栓塞、人工机械瓣膜替换患者增加,且均需长期抗栓治疗。当此类患者围手术期面对血栓和出血风险时,需要再次调整抗栓治疗计划。在ACCP8基础上,ACCP9精减去一些间接临床经验的推荐,对于没有试验证据的情况给予评论而不是推荐。相比于第八版,此次指南对于不确定的治疗和获益,在推荐的同时指出“反对”某项治疗。