Pharmacologic and pharmacogenetic associations with recurrent venous thrombosis

药理学和药物遗传学与复发性静脉血栓形成的关联

• 批准号: 7691281
• 负责人: NICHOLAS L SMITH
• 金额: $ 56.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691281
• 关键词: Address; Adrenergic Receptor; Adrenergic beta-Antagonists; Adult; Age-Years; Antigens; Biological Markers; Blood; Characteristics; Cholesterol Esters; Clinical; Clinical Trials; Coagulation Process; Cohort Studies; Collection; Comorbidity; Compression Stocking; Data; Data Collection; Deep Vein Thrombosis; Development; Elderly; Enrollment; Enzymes; Event; Factor VIII; Family history of; Female; Fibrin; Fibrin fragment D; Generations; Genes; Genetic; Health; Healthcare; Hemorrhage; Hemostatic Agents; Hemostatic function; Inflammatory; Inherited; Intervention; Length; Life; Measures; Mechanics; Medical Records; Metabolism; Observational Study; Oxidoreductase; P-Selectin; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacologic Substance; Pharmacy facility; Plasma; Population; Prevention; Prophylactic treatment; Proteins; Prothrombin; Publishing; Pulmonary Embolism; Recurrence; Request for Applications; Risk; Risk Factors; Safety; Series; Specimen; Testing; Thrombosis; Variant; Venous Thrombosis; Warfarin; Washington; Woman; Women' s Health; Work; beta-adrenergic receptor; cohort; cytokine; experience; factor V Leiden; follow-up; gene interaction; genetic risk factor; improved; inhibitor/antagonist; insight; interest; male; member; men; middle age; population based; prevent; public health relevance; sex

DESCRIPTION (provided by applicant): The prevention of recurrent venous thrombosis (VT) is paramount among the clinical challenges currently facing practitioners treating VT. Identifying patients at risk is made difficult by the fact that risk factors for VT recurrence are poorly characterized. Only recently has there been insight into the acquired and inherited characteristics that influence subsequent risk of a new thrombotic event in adults with a confirmed first event. As a result, there is little evidence to inform and guide treatment and prophylaxis decisions. In addition, treatment options to prevent recurrent VT are limited. Pharmaceutical anti-coagulation interventions are most effective but advantages need to be weighed against the risk of life-threatening bleeding. Using a population- based inception cohort of 2,100 incident VT patients with longitudinal data on clinical characteristics and pharmaceutical treatments, we propose a set of pharmacoepidemiologic hypotheses related to recurrent VT. Of primary interest are HMG co-enzyme A reductase inhibitors (statins) and beta-adrenergic receptor blockers (beta- blockers), commonly used medications in middle-aged and elderly adults. There is accumulating evidence that statins and beta-blockers reduce pro-inflammatory cytokines and pro-coagulation hemostatic factors, leading to improved endothelial function and lower thrombotic risk. Epidemiologic evidence suggests that statins are associated with a decreased risk of incident VT but there are no data on statins or beta-blockers and VT recurrence. Our primary hypotheses are that beta-blocker therapy and statin therapy lower the risk of recurrent VT after a first event. We are also proposing several secondary aims addressing biomarkers and genetics and recurrent VT. The setting for the study is Group Health, a large integrated healthcare organization in Western Washington State where the average length of enrollment among person with incident VT has been 20.8 years. This study builds upon our previous work of VT in women to produce a cohort of 2,100 incident VT events that occurred between 2002 and 2010. Using the detailed clinical and pharmacy information collected prospectively in Group Health medical records and pharmacy files, the 2,100 male and female subjects 30-89 years of age will be followed for an average of 7 years to identify pharmacoepidemiologic risks for the development of a subsequent DVT and PE. The identification of new drugs with a demonstrated safety record that also lower the risk of recurrent VT may have clinical utility. Existing clinical trial data on statin and beta- blocker treatments are not likely to answer the question of VT recurrence and few population-based observational studies of VT have complete and unbiased assessment of statin and beta-blocker use to prospectively evaluate risk. Public Health Relevance: Little is know about factors that are associated with the recurrence of venous thrombosis. Using a population-based inception cohort of 2,100 incident venous thrombosis patients on whom we will have complete baseline and longitudinal follow-up of clinical characteristics and pharmaceutical treatments, we propose a series of pharmacoepidemiologic hypotheses related to recurrent venous thrombosis in an adult population as primary aims.

描述（由申请人提供）： 预防复发性静脉血栓形成（VT）至关重要，这是当前正在治疗VT的从业者面临的临床挑战。由于VT复发的危险因素的特征很差，因此很难识别有风险的患者。直到最近，才洞察获得的和遗传的特征，这些特征会影响成年人的新血栓事件的随后风险，并确认了第一事件。结果，几乎没有证据可以告知和指导治疗和预防决策。此外，预防复发VT的治疗选择受到限制。药物抗凝干预措施是最有效的，但需要权衡危及生命的出血风险。使用基于人群的成立队列，由2,100例有纵向数据的事件VT患者进行有关临床特征和药物治疗的纵向数据，我们提出了一组与复发性VT相关的药物ePIDEMIologic假设。主要感兴趣的是HMG共生A还原酶抑制剂（他汀类药物）和β-肾上腺素能受体阻滞剂（β受体阻滞剂），这是中年和老年人的常用药物。有积极的证据表明，他汀类药物和β受体阻滞剂减少了促炎的细胞因子和促凝结止血因素，从而改善了内皮功能和降低血栓形成风险。流行病学证据表明，他汀类药物与出现VT的风险降低有关，但没有关于他汀类药物或β受体阻滞剂和VT复发的数据。我们的主要假设是，β受体阻滞剂疗法和他汀类药物疗法在第一次事件后降低了复发性VT的风险。我们还提出了一些次要目标，以解决生物标志物，遗传学和复发性VT。该研究的设置是Group Health，这是一个在华盛顿州西部的大型综合医疗组织，在该州，事件VT患者的平均入学时间为20。8年。 This study builds upon our previous work of VT in women to produce a cohort of 2,100 incident VT events that occurred between 2002 and 2010. Using the detailed clinical and pharmacy information collected prospectively in Group Health medical records and pharmacy files, the 2,100 male and female subjects 30-89 years of age will be followed for an average of 7 years to identify pharmacoepidemiologic risks for the development of a subsequent DVT and PE.鉴定具有安全记录的新药，也降低了复发性VT的风险可能具有临床实用性。关于他汀类药物和β受体疗法的现有临床试验数据不太可能回答VT复发的问题，对VT的基于人群的观察性研究很少，对他汀类药物和β受体阻滞剂的使用无偏见，以评估风险。公共卫生相关性：对与静脉血栓形成复发有关的因素知之甚少。使用基于人群的成立队列组成的2100例事故静脉血栓形成患者，我们将对临床特征和药物治疗进行完整的基线和纵向随访，我们建议在成人人群中与主要目标相关的一系列与静脉血栓形成相关的药物疾病学假设。