高齡老年患者冠狀動脈介入治療效果及風(fēng)險評估

Evan Kurniawan　張瑞巖

200025 上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院心內(nèi)科

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高齡老年患者冠狀動脈介入治療效果及風(fēng)險評估

Evan Kurniawan張瑞巖

200025 上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院心內(nèi)科

【摘要】高齡老年冠狀動脈粥樣硬化性心臟病(冠心病)患者合并疾病多，冠狀動脈病變復(fù)雜程度高，經(jīng)皮冠狀動脈介入治療(PCI)并發(fā)癥的發(fā)生率較高。對高齡老年患者PCI進(jìn)行風(fēng)險及預(yù)后評估非常重要。近年來，隨著PCI操作技術(shù)及策略的改進(jìn)，高齡老年患者PCI的成功率提高，相關(guān)并發(fā)癥發(fā)生率也有所下降。該文對80歲以上的高齡老年冠心病患者接受PCI的療效、手術(shù)風(fēng)險、并發(fā)癥及預(yù)后評估作一綜述。

冠狀動脈粥樣硬化性心臟病(冠心病)是高齡老年人的首要死亡原因[1]，接受經(jīng)皮冠狀動脈介入治療(PCI)的高齡老年冠心病患者比例逐年增高。80歲以上的冠心病患者行PCI手術(shù)風(fēng)險增加，既往隨機對照研究往往將該部分人群納入排除標(biāo)準(zhǔn)[2-3]。本文介紹80歲以上的高齡老年冠心病人群PCI療效、手術(shù)風(fēng)險及并發(fā)癥。

1高齡老年冠心病患者的臨床特征

高齡老年冠心病患者往往合并腎功能不全、高血壓、糖尿病、卒中等多種疾病[3-4]。研究發(fā)現(xiàn)，與年輕患者相比，高齡冠心病患者的高血壓、腦血管疾病、外周血管疾病及腎功能衰竭發(fā)生率較高(高血壓：61% 對 56%，腦血管疾?。?4% 對 7.8%，外周血管疾?。?5% 對 11%，腎功能衰竭：9.8%對4.8%；P<0.01)，且隨著年齡的增長多支血管病變及復(fù)雜病變的發(fā)生率也明顯升高[3]。另一項研究提示，年齡與冠狀動脈鈣化密切相關(guān)[5]。這些合并疾病及冠狀動脈復(fù)雜病變導(dǎo)致高齡老年患者PCI的難度加大，并發(fā)癥的發(fā)生率更高。

2高齡老年冠心病患者PCI的療效

2.1PCI 與單純藥物治療比較

TIME研究顯示，穩(wěn)定型心絞痛老年患者在藥物治療控制癥狀不佳時接受PCI，1年心血管不良事件發(fā)生率低于單純藥物治療(19% 對49%，P= 0.0001)[6]。隨訪4年顯示，接受PCI的高齡老年患者心血管不良事件發(fā)生率低于單純藥物治療(37% 對68%，P< 0.001)[7]。這說明高齡老年冠心病患者接受PCI比單純藥物治療效果更佳。

對高齡老年患者的臨床療效而言，維護(hù)及保留軀體功能是很重要的目標(biāo)。接受PCI的高齡老年患者比單純藥物治療患者的生活質(zhì)量更好，且軀體功能及心絞痛癥狀改善比年齡較輕患者更明顯。因此，高齡老年患者接受PCI獲益更大[8]。

2.2PCI 與冠狀動脈搭橋術(shù)(CABG)比較

目前，多支病變、左主干病變以及嚴(yán)重鈣化病變是CABG的指征。近年來, 隨著PCI操作技術(shù)的改進(jìn)、橈動脈徑路的普及、新一代藥物支架的產(chǎn)生、新型雙聯(lián)抗血小板藥物的出現(xiàn)及強化他汀類藥物的使用，高齡冠心病患者PCI成功率升高(>90%)，同時PCI相關(guān)并發(fā)癥顯著減少[9]。一項薈萃分析收集了65 000余例高齡老年患者(>80歲)，結(jié)果顯示，PCI組與CABG組30 d死亡率分別為5.4% 和7.3%，1年生存率分別為87%和86%，5年生存率分別為62% 和68%[10]。ASCERT研究顯示，2支或3支血管穩(wěn)定病變的高齡老年冠心病患者，上述兩種血運重建策略的1年生存率無顯著差異(6.5% 對6.2%)，但CABG組長期死亡率(隨訪4年)低于PCI組(16.4% 對20.8%)[11]。綜合上述研究結(jié)果，對于高齡老年患者復(fù)雜病變，PCI與CABG的療效相仿。

2.3特殊高齡老年患者PCI

研究提示，對于左主干病變患者，PCI與CABG的主要終點結(jié)果(死亡、心腦血管不良事件等)相仿。雖然PCI組再次血運重建比例較高，但CABG組腦卒中比例更高(1.5% 對4.3%，P= 0.03)[12]。Conrotto等[13]發(fā)現(xiàn)，左主干病變的高齡老年患者接受PCI及CABG術(shù)后遠(yuǎn)期死亡、腦血管意外及心肌梗死的發(fā)生率沒有差異。

雜交手術(shù)是將左乳內(nèi)動脈吻合于左前降支的旁路移植手術(shù)，并置入藥物涂層支架處理非前降支病變，具有較高的遠(yuǎn)期通暢率[14]。高齡老年患者因多合并某些臨床疾病難以耐受CABG術(shù)，可以考慮行雜交手術(shù)。

高齡老年非ST段抬高型心肌梗死(NSTEMI)患者應(yīng)盡早接受血運重建治療。Liistro等[15]發(fā)現(xiàn)，高齡NSTEMI患者未行早期血運重建治療，死亡率及再次心肌梗死發(fā)生率均高于非高齡患者。GRACE 研究提示，高齡老年NSTEMI患者行PCI術(shù)后6個月的死亡率比保守治療更低[16]。

目前臨床上高齡老年ST段抬高型心肌梗死(STEMI)患者急性期PCI血運重建率較低，老年癡呆、急慢性腎衰竭是導(dǎo)致該結(jié)果的主要原因[17-18]。研究發(fā)現(xiàn)，高齡老年STEMI患者如在12 h內(nèi)開通血管，超過90%的患者可恢復(fù)正常生活能力[19]。高齡老年患者在沒有絕對禁忌證的情況下，應(yīng)早期接受血運重建。

3圍術(shù)期并發(fā)癥

高齡冠心病患者病變更加復(fù)雜，臨床合并癥更多，并發(fā)癥發(fā)生率也更高。研究顯示，高齡老年冠心病患者PCI圍術(shù)期并發(fā)癥較年輕患者增加2～4倍[4]。這些圍術(shù)期并發(fā)癥包括死亡、心肌梗死、腦卒中、對比劑腎病及出血事件。

3.1對比劑腎病

PCI術(shù)后患者急性腎功能不全發(fā)生率達(dá)7%， 基線腎功能水平及造影劑用量是首要影響因素[20]。接受PCI的高齡老年患者，因基線腎功能較年輕患者差，其對比劑腎病的發(fā)生率較高，故需控制對比劑用量[21-22]。我國的專家共識推薦，術(shù)前6～12 h及術(shù)后4～12 h以100 mL/h的速度靜脈輸注生理鹽水能降低對比劑腎病的發(fā)生率[23]。

3.2出血風(fēng)險及抗血小板藥物選擇

高齡老年患者出血風(fēng)險高于年輕患者[24]。研究發(fā)現(xiàn)，高齡老年患者凝血功能亢進(jìn)，易引起急性支架內(nèi)血栓形成，同時老年患者存在凝血調(diào)節(jié)功能退化，導(dǎo)致纖溶亢進(jìn)，出血風(fēng)險亦較高[25-27]。另外，高齡老年患者體質(zhì)量偏輕，脂肪組織含量相對增加，對藥物治療的反應(yīng)更敏感，進(jìn)而放大不良反應(yīng)。PCI后的抗血小板治療是高齡老年患者出血的原因之一[28]。TRITON TIMI 38研究結(jié)果顯示，雖然普拉格雷能降低19%的缺血事件發(fā)生率，但該藥會導(dǎo)致出血風(fēng)險上升32%，尤其是>75歲的老年患者出血風(fēng)險更大，故不推薦>75歲的老年患者口服普拉格雷[29-30]。PLATO研究顯示，對于年齡>80歲的患者，與氯吡格雷相比，替格瑞洛能降低心源性死亡、心肌梗死及中風(fēng)等主要終點事件的發(fā)生率，且不增加出血風(fēng)險。這提示替格瑞洛或許是老年患者PCI術(shù)后抗血小板的更佳藥物[31]。

研究顯示，與肝素相比，高齡老年患者應(yīng)用比伐盧定能降低院內(nèi)出血風(fēng)險[32]。然而，一項隨機對照試驗的薈萃分析質(zhì)疑了比伐盧定較肝素出血風(fēng)險小的結(jié)論[33]。在絕大部分臨床中心，肝素仍然是PCI術(shù)中抗血栓形成的基礎(chǔ)藥物之一。一項包括6個評估GP Ⅱb/Ⅲa受體拮抗劑療效的大型臨床試驗薈萃分析表明，GP Ⅱb/Ⅲa受體拮抗劑的益處隨著年齡的增加而下降，心血管凈獲益率下降<5%，但主要出血時間增加了70%[34]。因此，高齡老年患者應(yīng)用此類藥物時應(yīng)酌情減量。

近年來，由于橈動脈穿刺并發(fā)癥發(fā)生率較股動脈穿刺更低，介入醫(yī)生傾向于選擇橈動脈作為首選穿刺點。臨床研究顯示，高齡老年患者經(jīng)橈動脈穿刺較經(jīng)股動脈穿刺住院并發(fā)癥發(fā)生率更低[35-37]。80歲以上患者經(jīng)橈動脈穿刺行旋磨術(shù)治療，手術(shù)成功率可達(dá)90%以上[38]。因此，高齡老年患者接受PCI治療可以選擇橈動脈穿刺途徑。

4結(jié)語

對高齡老年冠心病患者，年齡不應(yīng)該成為影響選擇PCI治療的決定因素。接受PCI的高齡老年患者需要根據(jù)其冠狀動脈病變的嚴(yán)重程度、全身狀態(tài)、血栓和出血風(fēng)險，充分評估手術(shù)成功可能性、風(fēng)險及預(yù)后。

參考文獻(xiàn)

[1]Kung HC, Hoyert DL, Xu J,et al. Division of vital statistics. deaths: final data for 2005. National vital statistics reports[J]. Natl Vital Stat Rep,2008,56(10):1-120.

[2]Rosamond W, Flegal K, Friday G,et al. Heart disease and stroke statistics—2007 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee[J]. Circulation,2007,115(5):e69-e171.

[3]Wennberg DE, Makenka DJ, Sengupta A,et al. Percutaneous transluminal coronary angioplasty in the elderly: epidemiology, clinical risk factors, and in-hospital outcomes. The Northern New England Cardiovascular Disease Study Group[J]. Am Heart J,1999,137(4 Pt 1):639-645.

[4]Batchelor WB, Anstrom KJ, Muhlbaier LH, et al. Contemporary outcome trends in the elderly undergoing percutaneous coronary intervention: results in 7.472 octogenarians[J]. J Am Coll Cardiol,2000,36(3):723-730.

[5]Sangiorgi G, Rumberger JA, Severson A,et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology[J]. J Am Coll Cardiol,1998,31(1):126-133.

[6]TIME Investigators. Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial[J]. Lancet,2001,358(9286):951-957.

[7]Pfisterer M, Trial of invasive versus medical therapy in elderly patients investigators. Long-term outcome in elderly patients with chronic angina managed invasively versus by optimized medical therapy: four year follow-up of the randomized Trial of Invasive versus Medical therapy in Elderly patients (TIME)[J]. Circulation,2004,110(10):1213-1218.

[8]Spertus JA, Salisbury AC, Jones PG,et al. Predictors of quality of life benefit after percutaneous coronary intervention[J]. Circulation,2004,110(25):3789-3794.

[9]Moreno R，Salazar A，Banuelos C，et al. Effectiveness of percutaneous coronary interventions in nonagerian[J]. Am J Cardiol,2004,94(8):1058-1060.

[10]McKellar SH, Brown ML, Frye RL,et al. Comparison of coronary revascularization procedures in octogenarians: a systematic review and meta-analysis[J]. Nat Clin Pract Cardiovasc Med,2008,5(11):738-746.

[11]Weintraub WS, Grau-Sepulveda MV, Weiss JM,et al. Comparative effectiveness of revascularization strategies[J]. N Engl J Med,2012,366(16):1467-1476.

[12]Morice MC, Serruys PW, Kappetein AP, et al. Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial[J]. Circulation,2014,129(23):2388-2394.

[13]Conrotto F, Scacciatella P, D’Ascenzo F, et al. Long-term outcomes of percutaneous coronary interventions or coronary artery bypass grafting for left main coronary artery disease in octogenarians (from a Drug-Eluting stent for LefT main Artery registry substudy)[J]. Am J Cardiol,2014,113(12):2007-2012.

[14]Repossini A, Tespili M, Saino A, et al. Hybrid coronary revascularization in 100 patients with multivessel coronary disease[J]. Ann Thorac Surg,2014,98(2):574-581.

[15]Liistro F, Angioli P, Falsini G,et al. Early invasive strategy in elderly patients with non-ST elevation acute coronary syndrome: comparison with younger patients regarding 30 day and long term outcome[J]. Heart,2005,91(10):1284-1288.

[16]Devlin G, Gore J, Elliott J,et al. Management and 6-month outcome in elderly and very elderly patients with high-risk non-Stelevation acute coronary syndromes[J]. Eur Heart J,2008,29(10):1275-1282.

[17]Gharacholou SM, Alexander KP, Chen AY, et al. Implications and reasons for the lack of use of reperfusion therapy in patients with ST-segment elevation myocardial infarction: findings from the CRUSADE initiative[J]. Am Heart J,2010,159(5):757-763.

[18]李茂巍, 張必利, 鄭興,等. 高齡冠心病患者PCI后院內(nèi)死亡危險因素分析[J]. 國際心血管病雜志，2015，42(1):56-58.

[19]Christiansen EC, Wickstrom KK, Henry TD, et al. Comparison of functional recovery following percutaneous coronary intervention for ST elevation myocardial infarction in three age groups (<70, 70 to 79 and≥80 years)[J]. Am J Cardiol,2013,112(3):330-335.

[20]Jurado-Román A, Hernández-Hernández F, García-Tejada J,et al.Role of hydration in contrast-induced nephropathy in patients who underwent primary percutaneous coronary intervention[J]. Am J Cardiol,2015,115(9):1174-1178.

[21]Tsai TT, Patel UD, Chang TI, et al. Contemporary incidence, predictors, and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions: insights from the NCDR Cath-PCI registry[J]. JACC Cardiovasc Interv,2014,7(1):1-9.

[22]Liu Y, Liu YH, Chen JY, et al. Safecontrast volumes for preventing contrast-induced nephropathy in elderly patients with relatively normal renal function during percutaneous coronary intervention[J]. Medicine (Baltimore),2015,94(12):e615.

[23]中華醫(yī)學(xué)會心血管病學(xué)分會. 含碘對比劑在心血管疾病中臨床應(yīng)用的專家共識(2012)[J]. 中華心血管病雜志，2013，41(2)：94-98.

[24]Kinnaird TD, Stabile E, Mintz GS,et al. Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions[J]. Am J Cardiol,2003,92(8):930-935.

[25]Mari D, Mannucci PM, Copoola R,et al. Hypercoagulability in centenarians: the paradox of successful aging[J]. Blood,1995,85(11):3144-3149.

[26]Zahavi J, Jones NA, Leyton J,et al. Enhanced in vivo platelet “release reaction” in old healthy individuals[J]. Thromb Res,1980,17(3-4):329-336.

[27]Terres W, Weber K, Kupper W, et al. Age, cardiovascular risk factors and coronary heart disease as determinants of platelet function in men. A multivariate approach[J]. Thromb Res,1991,62(6):649-661.

[28]Vaughan L, Zurlo F, Ravussin E. Aging and energy expenditure[J]. Am J Clin Nutr,1991,53(4):821-825.

[29]Wiviott SD, Braunwald E, McCabe CH,et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes[J]. N Engl J Med,2007,357(20):2001-2015.

[30]朱建兵，張俊峰. 冠心病抗栓藥物新進(jìn)展[J]. 國際心血管病雜志，2014，41(3)：163-166.

[31]Cannon CP, Harrington RA, James S,et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study[J]. Lancet,2010,375(9711):283-293.

[32]Lemesle G, Bonello L, De Labriolle A,et al. Impact of bivalirudin use on in-hospital bleeding and six-months outcomes in octogenarians undergoing percutaneous coronary intervention[J]. Catheter Cardiovasc Interv,2009,74(3):428-435.

[33]Cavender MA, Sabatine MS. Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials[J]. Lancet,2014,384(9943):599-606.

[34]Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein Ⅱb/Ⅲa inhibitors in acute coronary syndromes: a meta-analysis of all major randomized clinical trials[J]. Lancet,2002,359(9302):189-198.

[35]Kim SM, Moliterno DJ. Ageless benefits of transradial access for percutaneous coronary revascularization[J]. Catheter Cardiovasc Interv,2015,86(6):973-974.

[36]Koutouzis M, Matejka G, Olivecrona G, et al. Radial vs. femoral approach for primary percutaneous coronary intervention in octogenarians[J]. Cardiovasc Revasc Med,2010,11(2):79-83.

[37]Lee HW, Cha KS, Ahn J, et al. Comparison of transradial and transfemoral coronary intervention in octogenarians with acute myocardial infarction[J]. Int J Cardiol,2016,202:419-424.

[38]Dahdouh Z, Roule V, Dugué AE, et al.Rotational atherectomy for left main coronary artery disease in octogenarians: transradial approach in a tertiary center and literature review[J]. J Interv Cardiol,2013,26(2):173-182.

(收稿：2016-02-01修回：2016-02-25)

(本文編輯：梁英超)

doi:10.3969/j.issn.1673-6583.2016.02.005

通信作者：張瑞巖, Email: rjzhangruiyan@aliyun.com