Elvin Kedhi  荷兰鹿特丹Maasstad医院

　　Elvin Kedhi  荷兰鹿特丹Maasstad医院心脏病学家，主要研究领域是心脏病的基础和临床研究，以及相关大型研究项目负责人。

　　近20年来经皮冠状动脉介入治疗（PCI）成为最常用的冠心病血管重建治疗方法，但临床试验显示，对于冠状动脉多支血管病变（MVD），冠状动脉旁路移植术（CABG）优于第1代药物洗脱支架（DES）PCI。CABG的获益主要是对于紫杉醇DES和心脏外科手术与PCI的协同作用（SYNTAX）评分中高危患者，而对SYNTAX评分低危患者无明显优势。第2代DES对MVD的效果明显优于第1代。XIENCE Ⅴ依维莫司洗脱冠状动脉支架系统的临床评估（SPIRIT）和可降解聚合物Biolimus洗脱支架与持久聚合物依维莫司洗脱支架比较（COMPARE）试验结果显示，使用第2代依维莫司洗脱支架能显著降低MVD患者的事件发生率，如果SYNTAX试验中，PCI组使用第2代DES，则效果不会比CABG差。

　　通过血流储备分数（FFR）评价冠状动脉狭窄血液动力学指导的治疗策略方法也进一步改善了MVD患者PCI的治疗效果。在血流储备分数对比造影指导下的PCI（FAME）试验中，使用FFR指导对MVD患者进行DES PCI治疗可使1年后包括死亡、非致死性心肌梗死和再次血运重建在内的复合终点发生率降低30%。

　　对于合并糖尿病的MVD患者，PCI治疗作用是另一正在热议话题。这些患者使用新1代DES的获益相对较小。近期，糖尿病患者未来血运重建评估--多支病变最佳治疗（FREEDOM）试验显示，对这部分患者，CABG和PCI相比，可使包括死亡、心肌梗死和卒中在内的主要终点发生率显著降低。而SYNTAX试验的糖尿病亚组分析显示，胰岛素依赖型糖尿病患者PCI效果更差。新的冠状动脉内影像技术可能能够识别高危病变，筛选更适合接受PCI治疗的合并糖尿病的MVD患者。

　　总之，DES技术的不断进步为PCI在MVD治疗中的地位提升创造了条件。PCI目前在SYNTAX评分中的低危患者能取得与CABG近似的结果。手术策略应由心脏团队讨论决定。合并糖尿病尤其是胰岛素依赖型糖尿病的MVD患者，应首选CABG。

　　Clinical outcomes after Percutaneous Coronary Intervention (PCI) has progressively improved over the last two decades and PCI， due to its less invasive nature， as compared to Coronary Artery By-pass Graft surgery(CABG)， has become the most used revascularization procedure for treatment of coronary atherosclerosis disease worldwide. However short- and long-term results from clinical trials show that in the setting of multivessel coronary disease (MVD) CABG is associated with a reduction in efficacy and safety endpoints compared to PCI with first-generation drug eluting stents (DES) (1). The benefit offered by CABG is mainly observed in patients with intermediate and high risk Syntax Scores while also at 5 years no significant reduction in primary endpoint was observed in the low Syntax Score subgroup. As mentioned above these results apply to outcomes in PCI performed with the first-generation paclitaxel-eluting stent， which has been found inferior when compared to the current generation of DES (2). Interestingly the benefit offered from the second-generation DES parallels the lesion complexity becoming more pronounced in MVD patients with complex disease. Indeed in the MVD subgroup of the COMPARE trail a relative rate reduction of 40 % was observed in favor of the everolimus-eluting stent (3). Based in the results of the SPIRIT (2) and COMPARE trial， Claessen et al， showed that use of the second generation everolimus-eluting stent would have significantly reduced the event rates in the PCI arm of the SYNTAX trial and was this stent used， instead of the first generation paclitaxel-eluting stent， the SYNTAX trial would have shown non inferiority(4).

　　In addition to the improvements on DES device technology， new treatment strategies， guided by hemodynamic assessment of the coronary stenosis by use of the fractional flow reserve (FFR)， have set a further step ahead in improving outcomes after PCI in treatment of MVD (5). Indeed in the FAME Trial， FFR guidance in patients with MVD undergoing PCI with DES was associated with a significant reduction (≈30%) in the rate of the composite end point of death， nonfatal myocardial infarction， and repeat revascularization at one year. For more recalculating Syntax Score by only incorporating ischemia-producing lesions as determined by FFR decreases the number of higher-risk patients and better discriminates risk for adverse events in patients with MVD undergoing PCI(6).Put on a clinical perspective these new developments in PCI technology and strategy may lead to further improvements in outcomes post PCI in patients with MVD as compared to CABG. Indeed the EXCEL trial， a large ongoing randomized trial comparing PCI versus CABG in setting of left main disease and concomitant MVD will hopefully provide a clear answer to this still burning and unsolved question.

　　The role of PCI in treatment of DM patients with MVD is another ongoing and hot debate. Indeed such patients are known to have worse outcomes after PCI than non-DM patients， and differently from what observed in the non-DM patients， the benefit offered from the new generation DES in these patients is less pronounced (7). Recently， the FREEDOM trial showed that CABG significantly reduces the rates of the primary endpoint: a composite of death， myocardial infarction and stroke， compared to PCI (8). However the results of this trial should be interpreted on the context of disease complexity of the patients enrolled. Indeed the almost 90% of the patients had 3 vessel disease with an average of > 5 treated lesions per patient， and therefore such complex patients even before these trial were referred for CABG. For more， as shown from the results of the DM subgroup analysis from the SYNTAX Trial， outcomes between PCI as compared to CABG are strongly impacted from the type of DM as stratified from insulin dependence， with non insulin-dependent DM relating to worse outcomes in the PCI arm (9).  Different DES studies have indeed shown worse outcomes with DES in insulin-dependent DM patients(10) while the non insulin-dependent DM patients tend to have similar outcomes as the non-DM patients after PCI treatment with modern DES. Such finding theoretically is expected to be true also in the PCI arm of the FREEDOM trail， however to date such analysis has not yet been presented. Indeed insulin-dependent DM patients represent the most severe subgroup of the DM patients， which is often associated with ongoing inflammation， diabetes-induced nephropathy and neuropathy of longer date and therefore the incidence and progression of MVD is more pronounced in these patients. Indeed， due to worse outcomes with DES， insulin-dependent DM patients presenting with MVD should strongly be considered for surgical revascularization. Independently from the type of DM， all DM patients have a higher tendency to adverse events than non-DM patients after PCI treatment. Such tendency is a consequence not only of higher rate of target lesion related events but also of the faster progression of atherosclerosis outside the target segment. It is for this reason that in DM with advanced MVD CABG might be associated with better results than PCI. However， new intracoronary imaging modalities， now under investigation， have possibly the potential to identify coronary segments that host atherosclerotic plaques that are at higher risk for future events. Further advances in these techniques in combination with earlier detection of atherosclerosis disease in DM patients by means of non-invasive imaging techniques as computed coronary tomography angiography， applied for screening purposes in these high-risk patients， might lead to a different approach in treatment of coronary disease in DM patients that might be more suitable for PCI.

　　In conclusion， new approaches and continuous improvement in DES technology have set the stage for a larger role of PCI in treatment of MVD. Although nowadays PCI might be associated with similar results， as with CABG， for the low and intermediate Syntax Score MVD， such revascularization decision should best be taken from a hart team composed from surgeons and interventional cardiologists. However CABG should strongly be considered in setting of MVD in DM， and especially insulin-dependent DM.

　　References:

　　1.Mohr FW， Morice MC， Kappetein AP， Feldman TE， Stahle E， Colombo A， et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised， clinical SYNTAX trial. Lancet. 2013 Feb 23;381(9867):629-38. PubMed PMID: 23439102.

　　2.Stone GW， Rizvi A， Newman W， Mastali K， Wang JC， Caputo R， et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. The New England journal of medicine. 2010 May 6;362(18):1663-74. PubMed PMID: 20445180.

　　3.Kedhi E， Joesoef KS， McFadden E， Wassing J， van Mieghem C， Goedhart D， et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet. 2010 Jan 16;375(9710):201-9. PubMed PMID: 20060578.

　　4.Claessen BE， Stone GW， Smits PC， Kedhi E， Kikkert WJ， Piek JJ， et al. Would SYNTAX have been a positive trial if XIENCE V had been used instead of TAXUS?: A meta-analysis of a first-generation vs. a second-generation drug-eluting stent system. Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2010 Sep;18(9):451-3. PubMed PMID: 20862241. Pubmed Central PMCID: 2941132.

　　5.Tonino PA， De Bruyne B， Pijls NH， Siebert U， Ikeno F， van’ t Veer M， et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. The New England journal of medicine. 2009 Jan 15;360(3):213-24. PubMed PMID: 19144937.

　　6.Nam CW， Mangiacapra F， Entjes R， Chung IS， Sels JW， Tonino PA， et al. Functional SYNTAX score for risk assessment in multivessel coronary artery disease. Journal of the American College of Cardiology. 2011 Sep 13;58(12):1211-8. PubMed PMID: 21903052.

　　7.Kedhi E， Gomes ME， Lagerqvist B， Smith JG， Omerovic E， James S， et al. Clinical impact of second-generation everolimus-eluting stent compared with first-generation drug-eluting stents in diabetes mellitus patients: insights from a nationwide coronary intervention register. JACC Cardiovascular interventions. 2012 Nov;5(11):1141-9. PubMed PMID: 23174638.

　　8.Farkouh ME， Domanski M， Sleeper LA， Siami FS， Dangas G， Mack M， et al. Strategies for multivessel revascularization in patients with diabetes. The New England journal of medicine. 2012 Dec 20;367(25):2375-84. PubMed PMID: 23121323.

　　9.Banning AP， Westaby S， Morice MC， Kappetein AP， Mohr FW， Berti S， et al. Diabetic and nondiabetic patients with left main and/or 3-vessel coronary artery disease: comparison of outcomes with cardiac surgery and paclitaxel-eluting stents. Journal of the American College of Cardiology. 2010 Mar 16;55(11):1067-75. PubMed PMID: 20079596.

　　10.Stone GW， Kedhi E， Kereiakes DJ， Parise H， Fahy M， Serruys PW， et al. Differential clinical responses to everolimus-eluting and Paclitaxel-eluting coronary stents in patients with and without diabetes mellitus. Circulation. 2011 Aug 23;124(8):893-900. PubMed PMID: 21824922.