尽管人口老龄化，但在接受经皮冠状动脉介入术（PCI）的85岁以上患者中，对药物洗脱支架（DES）对比金属裸支架（BMS）的相对有效性知之甚少。Wang及同事综述了来自471 006例接受PCI且年龄≥65岁的受试者的数据。年龄≥85岁的患者PCIs比例升高，但是在这个年龄组中DES的使用率降低最多。与BMS相比较，DES与较低的死亡率相关，然而，校正后的死亡率差异随年龄增长而缩小。相反，DES校正后的心肌梗死（MI）再住院风险比显著较低，且获益随着年龄的增长而增加。这些结果提示在年龄≥85岁的患者中，DES与BMS相比结果改善。

　　JACC 2012;59:105-12.

　　点评：85岁以上PCI患者中DES是否较BMS获益更多
　　Daniel Forman， Harvard Medical School
　　The question whether or not to use drug-eluting stents (DES) in very old adults has festered with clinical uncertainty.  DES use is associated with lower restenosis risk compared with bare metal stents (BMS).  However， the anti-proliferative drugs on DES also limit endothelialization， a property that increases likelihood of thrombosis against struts that remain exposed for a more prolonged duration compared with BMS.  In 2006， reports of late stent thrombosis associated with DES resulted in precipitous decline in their use.  However， extended dual anti-platelet therapy with aspirin and thienopyridine was then found to counterbalance the thrombogenic risks restoring the predominance of DES in percutaneous coronary interventions (PCI).  However， for very old adults it is unclear if the advantages associated with DES are outweighed by need for prolonged anti-platelet therapy.  Not only does aging fundamentally increase bleeding risks， but it is associated with increased likelihood of comorbidities (e.g.， atrial fibrillation， GI bleeding) that exacerbate bleeding hazards.  Many assert that BMS may be a better therapeutic option for very old CAD patients as dual anti-platelet therapy can be discontinued earlier with BMS， thereby lowering hemorrhagic risks.
　　While several studies have demonstrated predominant utility of DES over BMS in adults aged in their 70’s， similar efficacy in those aged 80 years and over has not been established due particularly to the under-enrollment of very old adults in pertinent PCI trials and a dearth of relevant data.  Wang et al. addresses the issue of DES efficacy in adults who are very old in a study of 471，006 patients aged 65 years and older who underwent acute and elective PCI between 2004 and 2008.  Long-term outcomes are assessed， comparing DES vs. BMS (median follow-up 640.8 ±423.5 days) relative to age strata (65 to 74 years [N=241 196， 51%]; 75 to 84 years [N=187，656， 40%]; and 85 years and older [N=42，154， 9%]).
　　The study shows reduced DES use in all age groups between 2005 and 2008， reflecting the prevailing concerns at that time regarding long-term thrombogenic risks.  The decline affected all age strata， but the largest declines occurred among patients aged 85 years and older.  In contrast， the proportion of patients ≥85 years undergoing PCI increased over the same time， i.e.， increasing from 7 to 9% among those undergoing elective PCI， and from 10 to 13% among those undergoing acute PCI.
　　With increasing age， PCI patients were more likely to have higher prevalence of HF and stroke and higher Charlson index (a measure of comorbidity).  Older patients also had more multi-vessel PCI.  Periprocedure glycoprotein IIb/IIIa inhibitor use decreased with age， while use of bivalirudin and low-molecular-weight protein heparin increased. DES were used more commonly in those with lower Charlson index scores and those undergoing multi-vessel PCI.
　　Overall， in-hospital mortality rates were significantly higher among patients aged ≥85 years compared with the younger PCI patients.  Patients ≥85 years also had the highest long-term mortality as well as highest rates of myocardial infarction rehospitalization and bleeding.
　　Despite such inherent age-related risks， Wang et al. show that DES patients had lower risk adjusted mortality than BMS patients in every age strata， i.e.， mortality 29% vs. 38% among patients aged ≥85 yrs (HR=0.8; 95% CI 0.77-0.83)， 17% vs. 25% in those aged 75 to 84 (HR=0.77; 95% CI 0.75-0.79) and 10% vs. 16% in those aged 65 to 74 (HR=0.73; 95% CI 0.71-0.75).  As patient age increased， the adjusted mortality difference narrowed (Pinteraction<0.001).
　　While myocardial infarction rehospitalization also increased in those aged ≥85 years， Wang et al show risk was relatively lower with DES， with greater difference associated with increasing age (Pinteraction<0.001).  Comparing DES and BMS patients， adjusted rate for myocardial infarction was 9% vs. 12% in those aged ≥85 years (HR=0.77 [95% CI 0.71-0.83])， 7% vs. 9% in those aged 75 to 84 years (HR=0.81 [95%CI 0.77-0.84]) and 7% vs. 8% in those aged 65 to 74 years (HR=0.84 [95% CI 0.80-0.88]).
　　The study stands out by showing that DES was associated with reduced mortality and myocardial infarction rehospitalization， with benefits extending to the large population aged ≥85 years， and without increases in long-term bleeding.  This study contrasts with many prior investigations in that reduced revascularization benefit was not associated with DES over BMS.
　　While the investigators used rigorous methodology to control for the effects of clinical confounders in an observational analysis， the fact that this study shows such significant mortality and MI benefits raises concerns that residual confounding effects may have still been pertinent， especially since randomized trials have not demonstrated similar MI or mortality benefit associated with DES.  It may not be possible to account for all the confounding factors that likely affect outcomes amidst the major shifts in practice patterns that occurred over the study period.
　　The lack of restenosis benefit is also notable， and may relate to the fact that the revascularization endpoint in this analysis included ’any revascularization’ rather than target vessel.
　　Regardless of these points， this study is noteworthy in showing that bleeding risks were similar between DES and BMS patients across all age groups.  DES was associated with therapeutic benefits that compared favorably with BMS without added bleeding risks for adults aged ≥85 years.
　　DES与BMS比较，能降低再狭窄风险，但由于药物的抗增殖作用会延迟支架的内皮化，导致支架内血栓的可能性延长。2006年晚期支架内血栓形成的报道使DES的使用急剧下降，然而随后发现延长双重抗血小板治疗（DAPT）疗程能对抗血栓形成风险，使DES的使用重新成为主流。但是在高龄人群中，DES的益处是否大于延长抗血小板治疗带来的出血风险仍有争议，许多人认为BMS对高龄冠心病患者更合适，因为可以提早结束DAPT。
　　这项研究调查的对象是在2004~2008年间行PCI的65岁以上患者，其中85岁以上者有42 154例，中位随访时间为640.8±423.5天。随着年龄的增加，更多患者合并心力衰竭、卒中和高Charlson指数（反映合并症的一种评分），同时多支病变更多。DES更多应用于低Charlson指数和多支病变。总体来说，85岁以上患者院内死亡率高于年龄较轻者，同时远期死亡率、MI再住院率和出血也是最高的。尽管高龄与这些风险相关，但在85岁以上患者中，DES校正风险后的死亡率、MI再住院率、MI发病率均低于BMS，同时远期出血事件并不增加。这一结果与之前多项研究提示的DES与BMS比较并无血运重建的优势相矛盾。
　　尽管研究者应用了严格的方法以控制观察性研究中的临床混杂因素，但如此显著的死亡率和MI获益仍然引起对剩余混杂因素可能作用的怀疑，特别是随机试验并没有证实相似的DES获益。由于这项研究期间临床干预模式的重大变化，阐明所有可能影响预后的混杂因素是不太可能的。
　　需要注意的是这项研究中再狭窄获益的缺如，这可能与血运重建终点包括“任何血运重建”而不是目标血管有关。
　　尽管有上述疑问，这项研究仍值得引起注意，它表明在所有年龄段中，DES与BMS的出血风险相似，DES在85岁以上患者中相对BMS的治疗获益并不增加出血风险。