Théroux P, Waters D, Lam J, Juneau M, McCans J
Montreal Heart Institute, QC, Canada.
N Engl J Med. 1992 Jul 16;327(3):141-5. doi: 10.1056/NEJM199207163270301.
Heparin is an effective, widely used treatment for unstable angina. Among patients enrolled in a double-blind, randomized, placebo-controlled trial comparing intravenous heparin, aspirin, both treatments, and neither during the acute phase of unstable angina, we encountered patients in whom unstable angina was reactivated after heparin was discontinued.
The study population included 403 of the original 479 patients in the trial who had completed six days of blinded therapy without refractory angina or myocardial infarction. After the discontinuation of therapy, clinical events, including reactivation of unstable angina and myocardial infarction occurring within 96 hours after hospitalization, were closely monitored.
Early reactivation occurred in 14 of the 107 patients who received heparin alone, as compared with only 5 patients in each of the other three study groups (P less than 0.01). These reactivations required urgent intervention (thrombolysis, angioplasty, or coronary-bypass surgery) in 11 patients treated with heparin alone, but in only 2 patients in the other groups combined (P less than 0.01). Four of the six patients who had a myocardial infarction during a reactivation of their disease were in the heparin group. Reactivations in this group occurred in a cluster a mean (+/- SD) of 9.5 +/- 5 hours after the discontinuation of the study drug but were randomly distributed over the initial 96 hours in the other three groups.
Although heparin is beneficial in treating unstable angina, the disease process may be reactivated within hours of the discontinuation of this drug. Concomitant therapy with aspirin may prevent this withdrawal phenomenon.
肝素是治疗不稳定型心绞痛的一种有效且广泛应用的药物。在一项双盲、随机、安慰剂对照试验中，纳入了不稳定型心绞痛急性期的患者，比较静脉注射肝素、阿司匹林、两者联合使用以及两者均不使用的疗效，我们发现部分患者在停用肝素后不稳定型心绞痛复发。
研究人群包括原试验中479例患者中的403例，这些患者完成了6天的盲法治疗，且无难治性心绞痛或心肌梗死。治疗中断后，密切监测临床事件，包括住院后96小时内不稳定型心绞痛的复发和心肌梗死的发生。
仅接受肝素治疗的107例患者中有14例出现早期复发，而其他三个研究组每组仅有5例（P<0.01）。仅接受肝素治疗的11例复发患者需要紧急干预（溶栓、血管成形术或冠状动脉搭桥手术），而其他组联合起来仅有2例（P<0.01）。疾病复发时发生心肌梗死的6例患者中有4例在肝素组。该组的复发集中在停用研究药物后平均（±标准差）9.5±5小时，但在其他三组中则在最初的96小时内随机分布。
虽然肝素对治疗不稳定型心绞痛有益，但在停用该药数小时内疾病进程可能会复发。阿司匹林联合治疗可能会预防这种撤药现象。
