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JAMA:药物有助心脏手术前维持血小板高抑制率

  1. 心脏手术
  2. 抗凝血浓度
  3. 血小板药物

来源:EurekAlert 2012-11-18 10:48

1月18日,刊登在《美国医学会杂志》上的一则研究"Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery"披露,与接受安慰剂的病人相比,那些在接受心脏手术之前停止使用诸如氯吡格雷等抗血小板药物以降低其出血风险,并接受静脉内给药的血小板抑制剂坎格雷洛的病人会取得更高的血小板抑制维持率。

1月18日,刊登在《美国医学会杂志》上的一则研究"Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery"披露,与接受安慰剂的病人相比,那些在接受心脏手术之前停止使用诸如氯吡格雷等抗血小板药物以降低其出血风险,并接受静脉内给药的血小板抑制剂坎格雷洛的病人会取得更高的血小板抑制维持率。

根据文章的背景资料:“噻吩并吡啶[抗血小板制剂]属于最广泛使用的处方药,但它们的使用会因为意外的手术需要而变得复杂。尽管血栓形成的风险会增加,治疗指南建议在手术前5-7天的时候停止使用噻吩并吡啶以降低出血风险。”然而,在诸如冠状动脉搭桥术(CABG)等手术之前提前停止抗血小板疗法则与缺血性并发症的增加有关。文章的作者写道,有必要给抑制血小板的策略进行界定以允许在病人与他们的手术之间有一个安全的“纽带”而使得手术的缺血性事件或出血性并发症的风险降至最低。坎格雷洛的特点是可快速、强效、具可预见性、并可逆地抑制血小板,并可快速抵消其功效,对这些类型的病人来说, 这都是理想的药效动力学性质。

佛罗里达大学杰克逊维尔分校的Dominick J. Angiolillo, M.D., Ph.D.及其同事开展了一项研究,旨在检查坎格雷洛是否是一种可在接受噻吩并吡啶治疗的病人向CABG手术过渡的一种有效且安全的药物。该随机化、多中心的试验包括了罹患急性冠脉综合症(ACS)或接受冠脉支架治疗并在等待CABG手术前接受过某种噻吩并吡啶治疗的210名病人。噻吩并吡啶被停用(按照建议在手术前5-7天停用),病人接着接受坎格雷洛或安慰剂至少48小时,而它们也在手术前1-6小时的时候停用。药物输注的时间中位数(中点)对坎格雷洛是2.8天,对安慰剂是3.4天。对有效性的主要检测是血小板反应性不到240 P2Y12反应单位(PRUs),而后者是每日都被评估的。过度的CABG手术相关性出血是主要的安全性终点。

在贯穿整个研究药物输注期间,血小板反应性不到240 PRU的病人百分比在坎格雷洛组(98.8% [83/84])要明显高于安慰剂组(19.0% [16/84])。文章的作者写道:“与安慰剂相比,坎格雷洛组的显示血小板反应性不到240 PRU的总体样本百分比、所有具有基线PRU值样本的病人及在研究药物输注期间维持高于60%血小板抑制率的全部病人样本等都更大。”

研究人员得出结论:“在这一试验中,坎格雷洛取得并维持了已知与比安慰剂更低的血栓形成事件风险有关的抑制血小板的标靶水平,而且没有出血性并发症的明显增多。我们的数据支持这样的假说,即静脉内给予坎格雷洛是在噻吩并吡啶停止后需要长时间抑制血小板P2Y12的等待心脏手术的病人中的一个可行的处置策略。”(生物谷Bioon.com)

Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery

Dominick J. Angiolillo, MD, PhD; Michael S. Firstenberg, MD; Matthew J. Price, MD; Pradyumna E. Tummala, MD; Martin Hutyra, MD; Ian J. Welsby, MD; Michele D. Voeltz, MD; Harish Chandna, MD; Chandrashekhar Ramaiah, MD; Miroslav Brtko, MD, PhD; Louis Cannon, MD; Cornelius Dyke, MD; Tiepu Liu, MD, PhD; Gilles Montalescot, MD; Steven V. Manoukian, MD; Jayne Prats, PhD; Eric J. Topol, MDfor the BRIDGE Investigators

Context Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding.

Objective To evaluate the use of cangrelor, an intravenous, reversible P2Y12 platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery.

Design, Setting, and Patients Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011.

Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery.

Main Outcome Measures The primary efficacy end point was platelet reactivity (measured in P2Y12 reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery–related bleeding.

Results The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 μg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery–related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor.

Conclusions Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition.

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