Vedantham Suresh, Goldhaber Samuel Z, Julian Jim A, Kahn Susan R, Jaff Michael R, Cohen David J, Magnuson Elizabeth, Razavi Mahmood K, Comerota Anthony J, Gornik Heather L, Murphy Timothy P, Lewis Lawrence, Duncan James R, Nieters Patricia, Derfler Mary C, Filion Marc, Gu Chu-Shu, Kee Stephen, Schneider Joseph, Saad Nael, Blinder Morey, Moll Stephan, Sacks David, Lin Judith, Rundback John, Garcia Mark, Razdan Rahul, VanderWoude Eric, Marques Vasco, Kearon Clive
From the Washington University School of Medicine, St. Louis (S.V., L.L., J.R.D., P.N., M.C.D., N.S., M.B.); Brigham and Women's Hospital, Harvard Medical School (S.Z.G.), and Massachusetts General Hospital, Harvard Medical School (M.R.J.) - all in Boston; McMaster University, Hamilton, ON (J.A.J., M.F., C.-S.G., C.K.), and McGill University, Jewish General Hospital, Montreal (S.R.K.) - all in Canada; the University of Missouri, St. Luke's Mid America Heart Institute, Kansas City (D.J.C., E.M.); St. Joseph's Vascular Institute, Orange (M.K.R.), and University of California, Los Angeles, Los Angeles (S.K.) - both in California; University of Michigan, Ann Arbor (A.J.C.); Cleveland Clinic Heart and Vascular Institute, Cleveland (H.L.G.); Rhode Island Hospital, Brown University, Providence (T.P.M.); Central DuPage Hospital, Winfield, IL (J.S.); University of North Carolina, Chapel Hill (S.M.); Reading Hospital, Reading, PA (D.S.); Henry Ford Hospital, Detroit (J.L.); Holy Name Hospital, Teaneck, NJ (J.R.); Christiana Care Hospital, Newark, DE (M.G.); St. Elizabeth's Regional Medical Center, Lincoln, NE (R.R., E.V.); and Pepin Heart Center, Tampa, FL (V.M.).
N Engl J Med. 2017 Dec 7;377(23):2240-2252. doi: 10.1056/NEJMoa1615066.
The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome.
We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up.
Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups.
Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).
尽管接受了抗凝治疗，但近端深静脉血栓形成的患者仍经常发生血栓后综合征。药物机械导管定向溶栓（以下简称“药物机械溶栓”）可迅速清除血栓，并被认为可降低血栓后综合征的风险。
我们将692例急性近端深静脉血栓形成患者随机分为两组，分别接受单纯抗凝治疗（对照组）或抗凝加药物机械溶栓治疗（通过导管介导或设备介导将重组组织型纤溶酶原激活剂注入血栓内并进行血栓抽吸或破碎，可选择或不选择置入支架）。主要结局是在随访6至24个月期间发生血栓后综合征。
在6至24个月期间，血栓后综合征患者的百分比在组间无显著差异（药物机械溶栓组为47%，对照组为48%；风险比为0.96；95%置信区间[CI]为0.82至1.11；P = 0.56）。药物机械溶栓导致10天内发生更多的严重出血事件（患者比例分别为1.7%和0.3%，P = 0.049）,但在24个月的随访期内，复发性静脉血栓栓塞无显著差异（药物机械溶栓组为12%，对照组为8%，P = 0.09）。药物机械溶栓组18%的患者发生中重度血栓后综合征，而对照组为24%（风险比为0.73；95%CI为0.54至0.98；P = 0.04）。在随访的6、12、18和24个月时，药物机械溶栓组的血栓后综合征严重程度评分低于对照组（每个时间点Villalta评分比较，P<0.01），但治疗组从基线到24个月的生活质量改善情况无显著差异。
在急性近端深静脉血栓形成患者中，抗凝治疗加用药物机械导管定向溶栓并不能降低血栓后综合征的风险，但会增加严重出血的风险。（由美国国立心肺血液研究所等资助；ATTRACT临床试验注册号，NCT00790335。）
