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
基本信息
- 批准号:8307828
- 负责人:
- 金额:$ 61.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-09-26 至 2015-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdrenergic ReceptorAdrenergic beta-AntagonistsAdultAge-YearsAntigensBiological MarkersBloodCharacteristicsCholesterol EstersClinicalClinical TrialsCoagulation ProcessCohort StudiesCollectionComorbidityCompression StockingDataData CollectionDeep Vein ThrombosisDevelopmentElderlyEnrollmentEnzymesEpidemiologyEventFactor VIIIFamily history ofFemaleFibrinFibrin fragment DGenerationsGenesGeneticHealthHealthcareHemorrhageHemostatic AgentsHemostatic functionInflammatoryInheritedInterventionLengthLifeMeasuresMechanicsMedical RecordsMetabolismObservational StudyOxidoreductaseP-SelectinPathway interactionsPatientsPersonsPharmaceutical PreparationsPharmacogeneticsPharmacologic SubstancePharmacy facilityPlasmaPopulationPreventionProphylactic treatmentProteinsProthrombinPublishingPulmonary EmbolismRecurrenceRequest for ApplicationsRiskRisk FactorsSafetySeriesSpecimenTestingThrombosisVariantVenous ThrombosisWarfarinWashingtonWomanWomen&aposs HealthWorkbeta-adrenergic receptorcohortcytokineexperiencefactor V Leidenfollow-upgene interactiongenetic risk factorimprovedinhibitor/antagonistinsightinterestmalemembermenmiddle agepopulation basedpreventpublic health relevancesex
项目摘要
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 (VT) 是治疗 VT 的医生目前面临的临床挑战中最重要的。由于对 VT 复发的危险因素了解甚少,因此很难识别处于危险中的患者。直到最近,人们才深入了解影响首次确诊的成人发生新血栓事件的后续风险的获得性和遗传特征。因此,几乎没有证据可以指导和指导治疗和预防决策。此外,预防复发性室性心动过速的治疗选择也很有限。药物抗凝干预措施是最有效的,但需要权衡其优点与危及生命的出血风险。利用 2,100 名 VT 患者的基于人群的初始队列以及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 相关的药物流行病学假设。主要关注的是HMG辅酶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-阻滞剂),它们是中老年人常用的药物。越来越多的证据表明他汀类药物和β受体阻滞剂可减少促炎细胞因子和促凝血止血因子,从而改善内皮功能并降低血栓形成风险。流行病学证据表明他汀类药物可降低发生 VT 的风险,但没有关于他汀类药物或 β 受体阻滞剂与 VT 复发的数据。我们的主要假设是,β 受体阻滞剂治疗和他汀类药物治疗可降低首次发生 VT 后复发的风险。我们还提出了几个解决生物标志物、遗传学和复发性室性心动过速的次要目标。该研究的背景是 Group Health,这是华盛顿州西部的一家大型综合医疗机构,该机构的 VT 患者平均入组时间为 20.8 年。这项研究以我们之前对女性 VT 的研究为基础,生成了 2002 年至 2010 年间发生的 2,100 例 VT 事件队列。利用在团体健康医疗记录和药房档案中前瞻性收集的详细临床和药学信息,对 2,100 名男性和女性进行了研究。 30-89岁的受试者将被平均随访7年,以确定随后发生DVT和PE的药物流行病学风险。鉴定出具有已证实的安全记录并能降低 VT 复发风险的新药可能具有临床实用性。关于他汀类药物和 β 受体阻滞剂治疗的现有临床试验数据不太可能回答 VT 复发的问题,并且很少有基于人群的 VT 观察性研究对他汀类药物和 β 受体阻滞剂的使用进行完整和公正的评估,以前瞻性地评估风险。公共卫生相关性:人们对与静脉血栓复发相关的因素知之甚少。使用基于人群的初始队列,其中包括 2,100 名静脉血栓形成患者,我们将对这些患者的临床特征和药物治疗进行完整的基线和纵向随访,我们提出了一系列与成年人群中复发性静脉血栓形成相关的药物流行病学假设。目标。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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NICHOLAS L SMITH其他文献
NICHOLAS L SMITH的其他文献
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{{ truncateString('NICHOLAS L SMITH', 18)}}的其他基金
Genetic Discovery and Functional Validation to Identify Precursors of Clot Embolization in those with a Deep Vein Thrombosis
基因发现和功能验证,以识别深静脉血栓形成患者的血栓栓塞前体
- 批准号:
10414061 - 财政年份:2021
- 资助金额:
$ 61.32万 - 项目类别:
Genetic Discovery and Functional Validation to Identify Precursors of Clot Embolization in those with a Deep Vein Thrombosis
基因发现和功能验证,以识别深静脉血栓形成患者的血栓栓塞前体
- 批准号:
10579291 - 财政年份:2021
- 资助金额:
$ 61.32万 - 项目类别:
The Association of Vasomotor Symptoms with Thrombosis in Postmenopausal Women
绝经后妇女血管舒缩症状与血栓形成的关系
- 批准号:
8747858 - 财政年份:2014
- 资助金额:
$ 61.32万 - 项目类别:
The Association of Vasomotor Symptoms with Thrombosis in Postmenopausal Women
绝经后妇女血管舒缩症状与血栓形成的关系
- 批准号:
8890876 - 财政年份:2014
- 资助金额:
$ 61.32万 - 项目类别:
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:
8115913 - 财政年份:2008
- 资助金额:
$ 61.32万 - 项目类别:
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:
7895839 - 财政年份:2008
- 资助金额:
$ 61.32万 - 项目类别:
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 - 财政年份:2008
- 资助金额:
$ 61.32万 - 项目类别:
Estrogens and pharmacogenetic risks of venous thrombosis in postmenopausal women
绝经后妇女的雌激素和静脉血栓形成的药物遗传学风险
- 批准号:
7730104 - 财政年份:2004
- 资助金额:
$ 61.32万 - 项目类别:
Clotting genetic variant, hormones and venous thrombosis
凝血遗传变异、激素和静脉血栓形成
- 批准号:
6892153 - 财政年份:2004
- 资助金额:
$ 61.32万 - 项目类别:
Clotting genetic variant, hormones and venous thrombosis
凝血遗传变异、激素和静脉血栓形成
- 批准号:
7037591 - 财政年份:2004
- 资助金额:
$ 61.32万 - 项目类别:
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