Schulman S, Lindmarker P, Holmström M, Lärfars G, Carlsson A, Nicol P, Svensson E, Ljungberg B, Viering S, Nordlander S, Leijd B, Jahed K, Hjorth M, Linder O, Beckman M
Department of Hematology, Coagulation Unit, Karolinska University Hospital, Stockholm, Sweden.
J Thromb Haemost. 2006 Apr;4(4):734-42. doi: 10.1111/j.1538-7836.2006.01795.x.
The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear.
To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis.
In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry.
Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes.
The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.
静脉血栓栓塞症（VTE）后抗凝治疗的持续时间对长期发病率和死亡率的影响尚不清楚。
研究随机接受不同持续时间二级预防的VTE患者的长期后遗症。
在一项比较维生素K拮抗剂进行6周或6个月二级预防的多中心试验中，我们将原计划的2年随访延长至10年。患者每年就诊一次，在最后一次就诊时对血栓后综合征（PTS）进行临床评估。复发性血栓栓塞由一位对治疗分配不知情的放射科医生判定。死亡原因从瑞典死亡登记处获取。
在随机分组的897例患者中，545例在10年随访时可进行评估。发生严重PTS的概率为6%，56.3%的评估患者出现了PTS的任何迹象。多变量分析显示，老年和出院时循环功能受损的迹象是10年后发生PTS的基线独立危险因素。29.1%的患者发生复发性血栓栓塞，男性、老年患者、具有永久性触发危险因素（尤其是基线存在静脉功能不全）、出院时静脉循环功能受损迹象、近端深静脉血栓形成或肺栓塞的患者发生率更高。28.5%的患者死亡，死亡率高于预期，标准化发病比（SIR）为1.43（95%CI 1.28 - 1.58），主要是因为癌症导致的死亡率高于预期（SIR 1.83；95%CI 1.44 - 2.23）或心肌梗死或中风导致的死亡率高于预期（SIR 1.28；95%CI 1.00 - 1.56）。抗凝持续时间对任何长期结局均无统计学显著影响。
VTE首次发作后10年内的发病率和死亡率很高，将二级预防从6周延长至6个月并不能降低发病率和死亡率。需要一种降低VTE复发以及动脉疾病死亡率的策略。
