Cundiff David Keith
Los Angeles County Hospital, USC Medical Center, Long Beach, California, USA.
Medscape J Med. 2008;10(11):258. Epub 2008 Nov 11.
In vitro studies and anecdotal clinical reports have suggested that clinically significant rebound hypercoagulability may occur after discontinuation of oral anticoagulants (OACs), such as vitamin K antagonists and ximelagatran, for venous thromboembolism (VTE).
Assess the extent to which rebound hypercoagulability-related VTE recurrences occur in the 2 months following discontinuation of OACs.
Published, randomized controlled trials (RCTs) of OAC treatment of VTE.
RCTs of varying durations of OAC treatment of VTE that include VTE recurrence (or extension) data for more than 2 months after discontinuation of anticoagulants.
Rates of VTE recurrences (1) while taking OACs, (2) within 2 months of discontinuing OACs, and (3) from > 2 months until the end of the study were extracted along with major bleeding episodes while on OACs. The rate of VTE recurrences possibly attributable to rebound hypercoagulability was estimated by subtracting the VTE recurrence rate after the 2-month rebound period from the rate during the rebound period.
In 20 trials (n = 5822), VTE recurrences were 2.62 times as frequent in the 2 months following discontinuation of OACs as subsequently (1.57% VTE recurrences per month falling to 0.56% per month, odds ratio = 2.62, 95% confidence interval: 2.19-3.14), corresponding to 2.02% of patients with rebound hypercoagulability-related VTE recurrences (1.57% per month - 0.56% per month x 2 months = 2.02%). In the 11 trials with evaluable data from the shorter- and longer-duration OAC arms, total adverse events (VTE recurrences plus major bleeding) over the entire durations of the trials were not significantly different.
Rebound hypercoagulability accounts for about 2% of patients having recurrent VTE in the first 2 months after discontinuing OACs. RCTs evaluating the efficacy of OACs should include data for at least 2 months following OAC treatment. Increasing the duration of OAC treatment does not reduce the overall adverse events.
体外研究和临床轶事报告表明，停用口服抗凝剂（OACs），如维生素K拮抗剂和希美加群，用于治疗静脉血栓栓塞（VTE）后，可能会出现具有临床意义的反弹性高凝状态。
评估停用OACs后2个月内与反弹性高凝状态相关的VTE复发情况。
已发表的OAC治疗VTE的随机对照试验（RCTs）。
不同疗程的OAC治疗VTE的RCTs，包括抗凝剂停用后2个月以上的VTE复发（或扩展）数据。
提取VTE复发率（1）服用OACs期间，（2）停用OACs后2个月内，以及（3）从2个月后至研究结束时，以及服用OACs期间的大出血事件。通过从反弹性高凝状态期的复发率中减去2个月反弹性高凝状态期后的VTE复发率，来估计可能归因于反弹性高凝状态的VTE复发率。
在20项试验（n = 5822）中，停用OACs后2个月内的VTE复发频率是随后的2.62倍（VTE复发率从每月1.57%降至每月0.56%，比值比 = 2.62，95%置信区间：2.19 - 3.14），相当于2.02%的患者出现与反弹性高凝状态相关的VTE复发（每月1.57% - 每月0.56%×2个月 = 2.02%）。在11项具有来自短期和长期OAC治疗组可评估数据的试验中，试验整个疗程的总不良事件（VTE复发加大出血）无显著差异。
反弹性高凝状态约占停用OACs后前2个月VTE复发患者的2%。评估OACs疗效的RCTs应包括OAC治疗后至少2个月的数据。延长OAC治疗疗程并不能减少总体不良事件。
