Interventional Cardiology Program, Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
Circulation. 2010 Dec 7;122(23):2411-8. doi: 10.1161/CIRCULATIONAHA.110.950733. Epub 2010 Nov 22.
Secretory phospholipase A(2) (sPLA(2)) may play a role in myonecrosis after elective percutaneous coronary intervention (PCI). Inhibition of this enzyme may have a beneficial effect. The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA(2) would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention.
Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. The primary end point was elevation of troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18 to 24 hours after percutaneous coronary intervention. Mean age was 63±10 and 64±10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior myocardial infarction for the varespladib and placebo groups, respectively. The primary end point occurred in 75% of varespladib and 63% of placebo patients (P=0.14). Troponin I 3 times the upper limit of normal was observed in 57% and 50% (P=0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and 3% (P=0.018). Median (first and third quartiles) change in high-sensitivity C-reactive protein in these 2 groups was 0.65 mg/L (-0.18 and 1.48) and 0.70 mg/L (0.00 and 1.50) at 18 to 24 hours (P=0.81) and 0.20 mg/L (-0.70 and 1.40) and 0.60 mg/L (-0.12 and 1.72) at 3 to 5 days (P=0.23), whereas change in sPLA(2) activity at 3 to 5 days in a subset was -2.85 ng/ml (-3.40 and -1.85) and 0.25 ng/ml (-0.20 and 0.85) (P<0.001).
Inhibition of sPLA(2) by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.
分泌型磷脂酶 A(2)（sPLA(2)）可能在择期经皮冠状动脉介入治疗（PCI）后的心肌坏死中发挥作用。抑制这种酶可能会产生有益的效果。本研究的中心假设是，小分子 sPLA(2)抑制剂瓦瑞昔布治疗可减少择期经皮冠状动脉介入治疗后心脏生物标志物的术后释放。
2007 年 10 月至 2009 年 6 月，144 例稳定型患者被随机分配到 II 期试验中，分别接受瓦瑞昔布 500mg PO BID 或安慰剂，在择期 PCI 前 3-5 天和 5 天内使用。主要终点是在 PCI 后 6 至 8 小时或 18 至 24 小时时，肌钙蛋白 I 或肌酸激酶-MB 升高超过正常值上限。平均年龄为 63±10 岁和 64±10 岁，瓦瑞昔布组和安慰剂组分别有 38%和 42%的患者患有糖尿病，29%和 28%的患者有心肌梗死病史。主要终点在瓦瑞昔布组和安慰剂组中分别发生在 75%和 63%的患者中（P=0.14）。瓦瑞昔布组和安慰剂组中，肌钙蛋白 I 升高 3 倍的发生率分别为 57%和 50%（P=0.39），肌酸激酶-MB 升高 2 倍的发生率分别为 14%和 3%（P=0.018）。这两组在 18 至 24 小时时高敏 C 反应蛋白的中位数（第一和第三四分位数）变化分别为 0.65mg/L（-0.18 和 1.48）和 0.70mg/L（0.00 和 1.50）（P=0.81），在 3 至 5 天时分别为 0.20mg/L（-0.70 和 1.40）和 0.60mg/L（-0.12 和 1.72）（P=0.23），而在亚组中 3 至 5 天时 sPLA(2)活性的变化分别为-2.85ng/ml（-3.40 和-1.85）和 0.25ng/ml（-0.20 和 0.85）（P<0.001）。
在介入治疗前 3-5 天使用瓦瑞昔布抑制 sPLA(2)并不能减少与择期经皮冠状动脉介入治疗相关的围手术期心肌坏死。
