Collet Jean-Philippe, Montalescot Gilles, Steg Philippe Gabriel, Steinhubl Steven R, Fox Keith A A, Hu Ting Fei, Johnston S Claiborne, Hamm Christian W, Bhatt Deepak L, Topol Eric J
Inserm unit 937, institut de cardiologie, hôpital Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, bureau 236, 47, boulevard de l'Hôpital, 75013 Paris, France.
Arch Cardiovasc Dis. 2009 Jun-Jul;102(6-7):485-96. doi: 10.1016/j.acvd.2009.03.012. Epub 2009 Jun 11.
Late discontinuation of clopidogrel after an acute coronary syndrome or stent placement may be associated with a clinical rebound effect.
To describe the characteristics and evolution of patients non-compliant to study drug in the prospective, randomized, double-blind CHARISMA trial.
Of 15,603 patients aged 45 or older years with established atherothrombotic disease (coronary artery disease, stroke, peripheral arterial disease) or multiple cardiovascular risk factors, 2999 permanently interrupted (withdrawers) study drug (clopidogrel or placebo) during follow-up. The primary endpoint was first occurrence since randomization of myocardial infarction, stroke or cardiovascular death.
Withdrawers displayed a higher risk profile and rates of death/myocardial infarction/stroke (13.5% versus 5.6%; hazard ratio [HR]: 3.18; 95% confidence interval [CI]: 3.05-3.32; p<0.001) and severe bleeding (4.9% versus 0.7%; odds ratio [OR]: 7.42; 95% CI: 5.67-9.70; p<0.001) versus non-withdrawers. Death/myocardial infarction/stroke occurred after an average of 228 days (95% CI: 197-258) and was less frequent in patients assigned to clopidogrel versus placebo (9.7% versus 11.9%; HR: 0.80; 95% CI: 0.64-1.00; p=0.051); the rate of severe bleeding was the same (4.0% versus 4.3%; OR: 0.92; 95% CI: 0.65-1.32; p=0.66). Among withdrawers, initial clopidogrel treatment was an independent correlate of survival (HR: 0.74, 95% CI: 0.59-0.93; p=0.011), but not severe bleeding (OR: 0.94; 95% CI: 0.65-1.35; p=0.74). Kaplan-Meier curves for the primary endpoint suggested no rebound effect or disease reactivation after discontinuation of clopidogrel compared with placebo.
Patients who stopped medication had increased rates of ischaemic and bleeding events and mortality. Patients initially on clopidogrel had fewer ischaemic events than those on placebo; discontinuation was not associated with any clinically detectable rebound effect.
急性冠状动脉综合征或支架置入术后氯吡格雷的延迟停药可能与临床反跳效应有关。
描述前瞻性、随机、双盲的 CHARISMA 试验中不依从研究药物患者的特征及病情演变。
在 15603 例年龄 45 岁及以上、患有动脉粥样硬化血栓形成疾病（冠状动脉疾病、中风、外周动脉疾病）或多种心血管危险因素的患者中，2999 例在随访期间永久中断（停药者）研究药物（氯吡格雷或安慰剂）。主要终点是自随机分组后首次发生心肌梗死、中风或心血管死亡。
与未停药者相比，停药者具有更高的风险特征以及死亡/心肌梗死/中风发生率（13.5% 对 5.6%；风险比 [HR]：3.18；95% 置信区间 [CI]：3.05 - 3.32；p < 0.001）和严重出血发生率（4.9% 对 0.7%；比值比 [OR]：7.42；95% CI：5.67 - 9.70；p < 0.001）。死亡/心肌梗死/中风平均发生在 228 天之后（95% CI：197 - 258），且与服用氯吡格雷的患者相比，服用安慰剂的患者中该情况发生频率更低（9.7% 对 11.9%；HR：0.80；95% CI：0.64 - 1.00；p = 0.051）；严重出血发生率相同（4.0% 对 4.3%；OR：0.92；95% CI：0.65 - 1.32；p = 0.66）。在停药者中，初始氯吡格雷治疗是生存的独立相关因素（HR：0.74，95% CI：0.59 - 0.93；p = 0.011），但不是严重出血的相关因素（OR：0.94；95% CI：0.65 - 1.35；p = 0.74）。主要终点的 Kaplan - Meier 曲线表明，与安慰剂相比，氯吡格雷停药后未出现反跳效应或疾病再激活。
停药患者的缺血性和出血性事件发生率及死亡率增加。最初服用氯吡格雷的患者缺血性事件少于服用安慰剂的患者；停药与任何临床可检测到的反跳效应无关。
