利伐沙班
利伐沙班是一种口服抗凝剂,可直接、选择性地抑制 Xa 因子。在急性冠脉综合征患者中,利伐沙班能降低心血管性原因、心肌梗死或卒中所致死亡这个复合终点的风险,但增加大出血和颅内出血的风险。[71]Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9-19.http://www.nejm.org/doi/full/10.1056/NEJMoa1112277#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/22077192?tool=bestpractice.com
坎格雷洛 (Cangrelor)
坎格雷洛是一种静脉使用、直接作用的血小板二磷酸腺苷 P2Y12 抑制剂。与氯吡格雷相比,坎格雷洛显著减少任意原因导致的死亡、心肌梗死、缺血引起的血运重建或第 48 小时支架血栓形成的主要终点。[72]Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368:1303-1313.http://www.nejm.org/doi/full/10.1056/NEJMoa1300815#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/23473369?tool=bestpractice.com
沃拉帕沙 (Vorapaxar)
沃拉帕沙是一种口服竞争性 PAR-1 拮抗剂,能抑制凝血酶引起的血小板聚集。在急性冠脉综合征患者中,将沃拉帕沙加至标准治疗未能显著减少主要终点,但能显著增加包括颅内出血在内的大出血风险。[73]Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366:20-33.http://www.nejm.org/doi/full/10.1056/NEJMoa1109719#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/22077816?tool=bestpractice.com
REG1 抗凝系统
REG1 抗凝系统是一种以适体为基础的 IXa 因子抑制剂。已经开发其活性控制药物,用于各种急性心脏问题,例如急性冠脉综合征和经皮介入术。它包括一种活性适体药物 pegnivacogin 及其活性控制药物 anivamersen。[74]Vavalle JP, Cohen MG. The REG1 anticoagulation system: a novel actively controlled factor IX inhibitor using RNA aptamer technology for treatment of acute coronary syndrome. Future Cardiol. 2012;8:371-382.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739693/http://www.ncbi.nlm.nih.gov/pubmed/22420328?tool=bestpractice.comAnivamersen 是一种良好的逆转剂,能以快速的动力学与 pegnivacogin 结合并使其失活。[75]Povsic TJ, Vavalle JP, Aberle LH, et al. A phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial. Eur Heart J. 2013;34:2481-2489.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895957/http://www.ncbi.nlm.nih.gov/pubmed/22859796?tool=bestpractice.com已经用于 1 期和 2 期试验。[74]Vavalle JP, Cohen MG. The REG1 anticoagulation system: a novel actively controlled factor IX inhibitor using RNA aptamer technology for treatment of acute coronary syndrome. Future Cardiol. 2012;8:371-382.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739693/http://www.ncbi.nlm.nih.gov/pubmed/22420328?tool=bestpractice.com[75]Povsic TJ, Vavalle JP, Aberle LH, et al. A phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial. Eur Heart J. 2013;34:2481-2489.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895957/http://www.ncbi.nlm.nih.gov/pubmed/22859796?tool=bestpractice.com它是一种研究性药物,目前没有用于常规实践。一项试验旨在比较 PCI 后 REG1 与比伐芦定对结局的有效性,由于在接受 REG1 的患者中发生重度过敏反应,试验提前终止。[76]Lincoff AM, Mehran R, Povsic TJ, et al. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial. Lancet. 2016;387:349-356.http://www.ncbi.nlm.nih.gov/pubmed/26547100?tool=bestpractice.com
新一代口服抗凝药
针对多项随机对照试验的meta分析发现,口服抗因子Ⅹa或直接凝血酶抑制剂能显著增加急性冠状动脉综合征后接受抗血小板治疗患者的严重出血事件,但仅适度减少支架血栓或缺血事件。[77]Komócsi A, Vorobcsuk A, Kehl D, et al. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172:1537-1545.http://www.ncbi.nlm.nih.gov/pubmed/23007264?tool=bestpractice.com新一代口服抗凝药治疗临床净获益与常规治疗相比没有优势。
曲美他嗪 (Trimetazine)
是一种从代谢方面改善缺血的药物,不通过影响心肌氧耗和血液供应而发挥其抗缺血作用。此药物涉及多种机制,包括通过抑制脂肪酸代谢改善心肌葡萄糖利用,保持细胞内肌酸磷酸和ATP水平,降低缺血引起的细胞酸中毒和自由基损伤。
雷诺嗪 (Ranolazine)
通过抑制晚期钠电流发挥抗心绞痛效应。雷诺嗪单独或与β受体阻滞剂、钙通道阻滞剂或硝酸酯类药物联合用于对标准抗心绞痛治疗无效的慢性心绞痛患者。对于非 ST 段抬高型心肌梗死 (NSTEMI) 患者,将雷诺嗪添加至急性冠脉综合征的标准治疗对减少主要心血管事件无效。但是,雷诺嗪可减少缺血再发,并其无引起全因死亡或症状性心律失常的不良反应。[78]Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297:1775-1783.http://jama.jamanetwork.com/article.aspx?articleid=206779http://www.ncbi.nlm.nih.gov/pubmed/17456819?tool=bestpractice.com禁用于有QT间期延长疾病的患者。
尼可地尔
一种钾ATP通道开放剂,与硝酸酯类类似,可减轻症状,但尚未在NSTE-ACS患者中广泛验证。