Labrou Alexandra, Giannoglou George, Zioutas Dimitrios, Fragakis Nikolaos, Katsaris George, Louridas George
2nd Cardiology Department, G. Papanikolaou General Hospital, Exohi, Thessaloniki 57010, Greece.
Am J Cardiovasc Drugs. 2007;7(2):143-50. doi: 10.2165/00129784-200707020-00006.
The aim of this study was to evaluate whether the administration of trimetazidine, a piperazine derivative, to patients before and after percutaneous coronary intervention (PCI) minimizes the PCI-induced myocardial damage and improves left ventricular function 1 and 3 months after the procedure.
Fifty-two patients hospitalized for acute coronary syndromes (ACS) were included in this study. Patients were randomized into two groups: group A (trimetazidine group; n = 27) and group B (placebo group; n = 25). All patients received conventional antianginal therapy. In addition, group A patients received oral trimetazidine 20 mg every 8 hours, starting 15 days before PCI and continuing for 3 months after the procedure. For each patient, serum troponin I and creatinine kinase (CK)-MB levels were measured before PCI, then at 6, 24, and 48 hours after the procedure; a 2D cardiac echocardiogram was performed before PCI and at 1 and 3 months after the procedure.
Twenty-four hours after PCI, troponin I levels were >1 ng/mL in 7 of 27 patients (26%) of group A and 11 of 25 patients (44%) in group B. Fourty-eight hours after revascularization troponin levels remained elevated in 15% of patients in group A and in 32% of patients in group B. Twenty-two percent of patients in group A had CK-MB levels >5 ng/mL, 24 hours after PCI, compared with 40% of patients in group B; four patients of group A had high CK-MB levels prior to PCI procedure. Echocardiographic measurements before revascularization revealed that 11 of 27 patients (40%) in group A had an ejection fraction <50% versus 8 of 24 patients (33%) in group B . The number of patients with an ejection fraction <50% was significantly reduced in group A compared with group B at 1 and 3 months after PCI, i.e. 11% versus 16% (p = 0.046) at 1 month and 4% versus 16% (p = 0.017) at 3 months.A significant improvement in regional wall motion was noted after treatment with trimetazidine compared with placebo. One month after PCI, inferior left ventricular (LV) wall hypokinesia had improved in 4 of 6 trimetazidine recipients and in 4 of 14 placebo recipients (p = 0.014, group A vs group B). After 3 months inferior wall hypokinesia improved in four patients in group A versus six patients in group (p = 0.05). Similarly, anterior LV wall motion improved in 3 of 11 patients in group A and in 1 of 6 patients in group B at 1 month. After 3 months anterior wall hypokinesia had improved in eight patients in group A and in two patients in group B (p = 0.04, group A vs group B).
The metabolic agent trimetazidine appears to minimize myocardial reperfusion injury during PCI and improves global and regional wall motion at 1 and 3 months after PCI. This study was limited by small patient numbers and further studies are necessary to evaluate exact mechanisms of action and clinical implications of using trimetazidine in conjunction with PCI.
本研究旨在评估在经皮冠状动脉介入治疗(PCI)前后给予患者曲美他嗪(一种哌嗪衍生物)是否能使PCI引起的心肌损伤最小化,并改善术后1个月和3个月时的左心室功能。
本研究纳入了52例因急性冠状动脉综合征(ACS)住院的患者。患者被随机分为两组:A组(曲美他嗪组;n = 27)和B组(安慰剂组;n = 25)。所有患者均接受常规抗心绞痛治疗。此外,A组患者从PCI术前15天开始每8小时口服20 mg曲美他嗪,并在术后持续服用3个月。对每位患者在PCI术前、术后6、24和48小时测量血清肌钙蛋白I和肌酸激酶(CK)-MB水平;在PCI术前以及术后1个月和3个月进行二维心脏超声心动图检查。
PCI术后24小时,A组27例患者中有7例(26%)肌钙蛋白I水平>1 ng/mL,B组25例患者中有11例(44%)。血运重建术后48小时,A组15%的患者肌钙蛋白水平仍升高,B组为32%。PCI术后24小时,A组22%的患者CK-MB水平>5 ng/mL,而B组为40%;A组有4例患者在PCI术前CK-MB水平就较高。血运重建术前的超声心动图测量显示,A组27例患者中有11例(40%)射血分数<50%,而B组24例患者中有8例(33%)。与B组相比,A组在PCI术后1个月和3个月时射血分数<50%的患者数量显著减少,即1个月时分别为11%和16%(p = 0.046),3个月时分别为4%和16%(p = 0.017)。与安慰剂相比,曲美他嗪治疗后区域壁运动有显著改善。PCI术后1个月,6例接受曲美他嗪治疗的患者中有4例左心室(LV)下壁运动减弱情况得到改善,14例接受安慰剂治疗的患者中有4例(A组与B组相比,p = 0.014)。3个月后,A组有4例患者下壁运动减弱情况改善,B组有6例患者(p = 0.05)。同样,1个月时A组11例患者中有3例左心室前壁运动改善,B组6例患者中有1例。3个月后,A组有8例患者前壁运动减弱情况改善,B组有2例患者(A组与B组相比,p = 0.04)。
代谢药物曲美他嗪似乎能使PCI期间的心肌再灌注损伤最小化,并改善PCI术后1个月和3个月时的整体和区域壁运动。本研究受患者数量较少的限制,有必要进一步研究以评估曲美他嗪与PCI联合使用的确切作用机制和临床意义。