Combined antiplatelet and anticoagulant therapy: clinical benefits and risks

Summary.  The combination of anticoagulant and antiplatelet therapy is more effective than antiplatelet therapy alone for the initial and long-term management of acute coronary syndromes but increases the risk of bleeding. Antiplatelet therapy is often combined with oral anticoagulants in patients with an indication for warfarin therapy (e.g. atrial fibrillation) who also have an indication for antiplatelet therapy (e.g. coronary artery disease) but the appropriateness of such an approach is unresolved. Anticoagulation appears to be as effective as antiplatelet therapy for long-term management of acute coronary syndrome and stroke, and possibly peripheral artery disease, but causes more bleeding. Therefore, in such patients who develop atrial fibrillation, switching from antiplatelet therapy to anticoagulants might be all that is required. The combination of anticoagulant and antiplatelet therapy has only been proven to provide additional benefit over anticoagulants alone in patients with prosthetic heart valves. The combination of aspirin and clopidogrel is not as effective as oral anticoagulants in patients with atrial fibrillation, whereas the combination of aspirin and clopidogrel is more effective than oral anticoagulants in patients with coronary stents. Whether the benefits of triple therapy outweigh the risks in patients with atrial fibrillation and coronary stents requires evaluation in randomized trials.     

Dietary therapy for thrombotic diseases of artery and vein]

Dietary therapy for ameliorating hyperlipidemia consists of several means. First of all, energy restriction is important, especially when the patient is obese. Secondary, restriction of total fat and saturated fatty acid intake is necessary. Energy from fat should be less than 25% of total energy and S:M:P ratio is recommended to be around 1:1-2:1-1.5. Cholesterol intake should be restricted below 300 mg and intake of dietary fiber and vegetable proteins should be increased. Hemostatic factors play an important role in the vessel diseases. A fat-rich diet increases activated factor VII. Many studies have reported inverse association between atherosclerotic disease and n-3 fatty acid consumption. We should maintain the present level of n-3 PUFA intake in Japan by keeping the n-6/n-3 ratio around 4.     

Screening for inherited thrombotic disorders

Summary In order to determine a scheme for the screening of inherited thrombotic disorders, abnormalities considered as predisposing to thrombosis have been reviewed. Owing to the low prevalence of biological alterations, a selection of patients is required: documented venous thromboses, possibly at unusual sites (mesenteric vein, portal, cerebral veins), occurring before the age of 40 in patients with a positive family history of thromboses are relatively frequently associated with coagulation abnormalities. In addition, patients with skin necrosis at the initiation of oral anticoagulants, or with repeated superficial vein thrombosis or unexplained arterial occlusions at a young age might be included for screening. Tests have also to be selected. Some abnormalities, such as congenital deficiencies in antithrombin III, protein C and protein S, are recognized risk factors and have to be searched. Some others cannot be at present considered as definite risk factors (e.g., dysfibrinogenemias or deficiencies in factor XII), but their detection is easy by routine tests: prothrombin time, fibrinogen assay. Other abnormalities are recognized risk factors (or not) and need specific uncommon tests (e.g., study of fibrinolysis). Each time a biological abnormality is found, it is important to verify it is isolated since combined deficiencies have been observed and we should be able to answer the question whether the abnormality is the cause or the consequence of thrombosis, or a coincidence. Finally, in our experience, even in well selected patients, a coagulation disorder is detected in less than 30% of patients, so that new tests are needed to improve our knowledge in this field. Presented at the ‘2nd International Symposium on Standardization and Quality Control of Coagulation Tests: Implications for the Clinical Laboratory’, Rome, September 28–29, 1989.     

抗凝药物治疗的患者合并上尿路结石的处理

抗凝药的使用在一般人群明显增加,这促使外科医生在给长期抗凝治疗的患者手术时需要考虑血栓和出血的风险。对于服用抗凝药物合并上尿路结石的处理尤其比较棘手。本文回顾了服用抗凝药物治疗的患者合并尿路结石处理的文献。同时汇报了北京积水潭医院采用三步法经皮肾镜处理血栓栓塞高危风险长期服用抗凝和抗血小板药物合并上尿路结石的经验。     

Thrombolytic therapy for acute ischemic stroke

Current evidence suggests that, in a small subset of acute stroke patients who can be treated within 3 hours of symptom onset, the administration of tissue plasminogen activator (tPA) confers a modest outcome benefit, but that this benefit is associated with an increased risk of intracranial hemorrhage that can be severe or fatal. The data show that tPA therapy must be limited to carefully selected patients within established protocols. Further evidence is necessary to support the widespread application of stroke thrombolysis outside research settings. Until it is clear that the benefits of this therapy outweigh the risks, thrombolytic therapy for acute stroke should be restricted to use within formal research protocols or in monitored practice protocols that adhere to the NINDS (the rt-PA Stroke Study Group trial of the National Institute of Neurological Disorders and Stroke) eligibility criteria. All data on protocol compliance and patient outcomes should be collated in a central Canadian registry for the purposes of tracking safety and efficacy. Stroke thrombolysis should be limited to centers with appropriate neurological and neuro-imaging resources that are capable of administering treatment within 3 hours. In such centres, emergency physicians should identify eligible patients, initiate low risk interventions and facilitate prompt computed tomography. Only physicians with demonstrated expertise in neuroradiology should interpret head CT scans used to determine whether to administer thrombolytic agents to stroke patients. Neurologists should be directly involved prior to the thrombolytic administration.     

Thrombolytic therapy for acute myocardial infarction

Should thrombolytic therapy be used in all patients who have acute myocardial infarction? Is one agent more effective than another? How safe is thrombolytic therapy? In this article, the authors discuss thrombolytic agents currently available, examine the results of ongoing studies, and reflect on future developments in thrombolytic management of myocardial infarction.     

Oral anticoagulant use in addition to antiplatelet therapy for secondary prevention in acute coronary syndrome: current perspectives

Patients with acute coronary syndrome (ACS) are typically managed with long-term dual antiplatelet therapy of acetylsalicylic acid plus a P2Y₁₂ platelet receptor antagonist; however, although effective, the risk of another vascular event within 12 months remains at approximately 10%. Considerable efforts have been made to find improved therapeutic approaches to secondary prevention in ACS. The ATLAS ACS 2-TIMI 51 trial demonstrated that rivaroxaban (2.5 mg twice daily) significantly reduced recurrent vascular events, increased the risk of major bleeding but not the risk of fatal bleeding, and resulted in reduced rates of death from cardiovascular causes. These results formed the basis for approval in Europe of rivaroxaban (2.5 mg twice daily) in conjunction with standard antiplatelet therapy for the secondary prevention of ACS.     

The quality of oral anticoagulant therapy and recurrent venous thrombotic events in the Leiden Thrombophilia Study

BACKGROUND: The International Normalized Ratio (INR) target range is a relatively narrow range in which the efficacy of oral anticoagulant treatment, i.e. prevention of extension and recurrence of thrombosis, is balanced with the risk of hemorrhagic complications. Over the years, different INR target ranges have been implemented for individual indications, depending on their thrombotic potential. In most of the studies defining these INR targets, the treatment of the patients was aimed at a certain INR range, but in the analysis no account was taken of the time that the patients spent within this range in reality. METHODS: The Leiden Thrombophilia Study (LETS) is a population-based case-control study on risk factors for venous thrombosis, in which many genetic and acquired factors have been investigated. Our aim was to investigate the effect of the quality of the oral anticoagulant therapy for the initial venous thrombosis and its relationship with recurrence of thrombosis. Quality of anticoagulation was defined as the time spent at various INR levels during treatment, and we focused on the effect of sustained intensities above a certain INR in preventing recurrences later on. RESULTS: Two hundred and sixty-six patients with a total follow-up of 2495 patient-years were studied. The mean duration of the initial anticoagulant therapy was 194.5 days (range 48-4671). During follow-up, 58 recurrences were diagnosed (cumulative recurrence rate of 21.8% over 9 years). The mean INR during initial therapy was 2.90, with 90.3% [95% confidence interval (CI) 88.4-92.3%] of the time being spent above an INR of 2.0, and 39.1% (95% CI 35.5-42.7%) above an INR of 3.0. Patients who spent more time below the target range, or who had a shorter duration of anticoagulation, did not experience a higher risk of recurrence after the initial period of anticoagulation had passed. CONCLUSION: Provided that oral anticoagulant treatment is adequately managed, according to international guidelines, recurrent thrombosis cannot be ascribed to variation in the primary treatment. Further attempts to reduce the risk of recurrence should therefore be aimed at identifying other explanatory factors, and subsequently fine-tuning the target ranges.     

Benefits and risks of antiplatelet therapy. A retrospective study]

Seven hundred and forty-six patients with cerebral infarction (except those with cardiogenic embolism) were retrospectively studied to determine the effect of antiplatelet agents on the prevention of recurrence and the incidence of cerebral hemorrhage, as an adverse effect of the drugs. The average follow-up period was 26.5 months for the fatal cases and 41.3 months for the survivors. Cerebral infarction recurred in 41 patients (3.1%/year) during the period of administration of antiplatelet agents, while it occurred in 66 (5.4%/year) untreated patients (p less than 0.01). Cerebral hemorrhage occurred 14 times in 14 patients; 7 (0.5%/year) during the antiplatelet treatment and 7 (0.6%/year) during the period without antiplatelet agents. No evidence was found that cerebral hemorrhage was promoted by antiplatelet agents.     

Infectious endocarditis: immune disorders, differentiated therapy]

AIM: Immunological assessment of variants of infectious endocarditis (IE) and design of differentiated approach to the disease therapy. MATERIALS AND METHODS: Of 150 patients treated (90 males and 60 females, mean age 41.9 +/- 3.3 years) 28.7% and 71.3% had primary and secondary endocarditis, respectively. With chronization of the process, there was a trend to growing immune unbalance (IU). RESULTS: The IU in IE patients manifested with leukocytosis changing for leukopenia, reduced absolute and relative number of lymphocytes, complement, T- and B-lymphocytes, growing content of CIC, IgM, rheumatoid factor and cryoproteins. CONCLUSION: Besides antibacterial therapy, IE patients need immunocorrective and efferent therapy.