van der Wieken L R, Simoons M L, Laarman G J, Van den Brand M, Nijssen K M, Dellborg M, Hermens W, Vrolik W
Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands.
Int J Cardiol. 1995 Nov 24;52(2):125-34. doi: 10.1016/0167-5273(95)02476-d.
An open pilot study was performed to assess the safety and preliminary efficacy of ridogrel, a selective thromboxane-A2 synthetase inhibitor and thromboxane-A2/prostaglandin endoperoxide receptor blocker, as adjunct to thrombolysis, with alteplase and heparin. In 50 patients with acute myocardial infarction, 300 mg ridogrel was injected intravenously in addition to alteplase and heparin. Ridogrel was continued orally (300 mg) twice daily for 5 days. Patency rate at initial (90 min) angiography, defined as thrombolysis in myocardial infarction perfusion grades 2 or 3, was 86%. Rescue percutaneous transluminal coronary angioplasty was performed in 10 patients; immediate results were good in nine, while a large dissection occurred in one patient. New ischemia occurred in 10 patients within 24 h, and after the second angiogram in seven cases. Three underwent coronary artery bypass grafting and seven percutaneous transluminal coronary angioplasty without further complication. Patency rate at second angiography (between 6 and 24 h) was 94%. New Q-waves appeared in 56% of the patients; 36% had a non-Q-wave infarction and 8% had no enzyme rise. Enzymatic infarct size, estimated by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase released in 72 h, was substantially smaller than in comparable studies with rt-PA and heparin. One patient died due to a cerebrovascular hemorrhage. No other deaths occurred. Bleeding complications were seen in 18 patients (36%), necessitating blood transfusion in three. Reinfarction did not occur. Eventually 49 patients were discharged in good condition. Safety with regard to bleeding complications of ridogrel in conjunction with alteplase is about the same as that of aspirin. Immediate and late patency rates were high. Rescue percutaneous transluminal coronary angioplasty could be performed with relative safety and early reocclusion could be successfully dealt with by repeat percutaneous transluminal coronary angioplasty. Further studies with this or similar compounds seem warranted.
进行了一项开放性试验研究,以评估利多米尔(一种选择性血栓素 - A2合成酶抑制剂和血栓素 - A2/前列腺素内过氧化物受体阻滞剂)作为阿替普酶和肝素溶栓辅助药物的安全性和初步疗效。在50例急性心肌梗死患者中,除了阿替普酶和肝素外,还静脉注射了300毫克利多米尔。利多米尔持续口服(300毫克),每日两次,共5天。初始(90分钟)血管造影时的通畅率,定义为心肌梗死灌注分级为2级或3级的溶栓,为86%。10例患者接受了补救性经皮冠状动脉腔内血管成形术;9例患者的即刻效果良好,1例患者发生了大面积夹层。10例患者在24小时内出现新的缺血,7例患者在第二次血管造影后出现。3例患者接受了冠状动脉搭桥术,7例患者接受了经皮冠状动脉腔内血管成形术,无进一步并发症。第二次血管造影(6至24小时之间)时的通畅率为94%。56%的患者出现了新的Q波;36%的患者发生了非Q波梗死,8%的患者酶未升高。通过72小时内释放的α - 羟丁酸脱氢酶的累积量估计的酶促梗死面积,明显小于使用rt - PA和肝素的类似研究。1例患者因脑血管出血死亡。未发生其他死亡。18例患者(36%)出现出血并发症,3例患者需要输血。未发生再梗死。最终49例患者康复出院。利多米尔与阿替普酶联合使用时出血并发症的安全性与阿司匹林大致相同。即刻和晚期通畅率较高。补救性经皮冠状动脉腔内血管成形术可相对安全地进行,早期再闭塞可通过重复经皮冠状动脉腔内血管成形术成功处理。对这种或类似化合物进行进一步研究似乎是必要的。