One-Time versus Staged Multivessel Intervention in Intermediate to Very High-Risk Patients with Non-ST-Segment Elevation Acute Coronary Syndromes

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1 Original Article Print ISSN On-line ISSN Korean Circulation Journal One-Time versus Staged Multivessel Intervention in Intermediate to Very High-Risk Patients with Non-ST-Segment Elevation Acute Coronary Syndromes Xiaofan Yu, MD 1,2,3, Yi Li, MD 2, Qiancheng Wang, MD 1, Ming Liang, MD 2, Kai Xu, MD 2, and Yaling Han, MD 2 1 Deartment of Cardiology, The Second Hosital of Dalian Medical University, Dalian, Liao Ning, 2 Deartment of Cardiology, General Hosital of Shenyang Military Region, Shenyang, Liao Ning, 3 Deartment of Cardiology, Anhui Provincial Hosital, Hefei, Anhui, China Background and Objectives: To comare clinical outcomes of staged versus one-time ercutaneous coronary intervention (PCI) in intermediate to very high-risk atients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) and multivessel coronary disease (MVD). Subjects and Methods: 1531 NSTE-ACS atients with multivessel PCI and meeting the criteria of intermediate to very high risk were screened from a rosectively registered database obtained from General Hosital of Shenyang Military Region between 8 and 12. They were categorized into one-time PCI (n=859) and staged PCI (n=672) according to intervention strategy. The rimary outcomes included a 3-year major adverse cardiac event (MACE), a comosite of cardiac death, myocardial infarction (MI), and target vessel revascularization. Results: At 3 years, no significant differences in MACE (.8% vs. 19.7%, =.68) and cardiac death/mi (7.1% vs. 9.1%, =.129) were observed between the two grous. After roensity score matching, there was no statistical significance in MACE (18.9% vs. 21.8%, =.249); whereas cardiac death/mi was significantly lower in the staged PCI grou (7.% vs.11.1%, =.33). Ninety-day landmark analysis showed that the staged PCI grou had a lower 9-day incidence of MACE (1.2% vs. 3.3%, =.37) and cardiac death/mi (.7% vs. 2.6%, =.31). For the 9-day to 3-year follow-u eriod, the incidences of MACE (17.9% vs. 19.1%, =.641) and cardiac death/mi (6.3% vs. 8.7%, =.191) were similar in both grous. Conclusion: In intermediate- to very high-risk NSTE-ACS atients with MVD, staged PCI is suerior to one-time PCI in terms of cardiac death/mi. (Korean Circ J 16;46(6): ) Key words: Acute coronary syndromes; Coronary artery disease; Percutaneous coronary intervention. Introduction Non-ST-segment elevation acute coronary syndromes (NSTE-ACS) Received: December 13, 15 Revision Received: Aril 28, 16 Acceted: May 31, 16 Corresondence: Yaling Han, MD, General Hosital of Shenyang Military Region, 83 Wenhua Road, Shenyang Liaoning Province, China Tel: , Fax: hanyaling@263.net The authors have no financial conflicts of interest. This is an Oen Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (htt://creativecommons. org/licenses/by-nc/3.) which ermits unrestricted non-commercial use, distribution, and reroduction in any medium, rovided the original work is roerly cited. are the most frequent manifestation of acute coronary syndromes (ACS). Its morbidity and mortality stays high and even equal to those of atients with ST-segment elevation myocardial infarction (STEMI) during long-term follow-u. 1)2) Current guidelines 2)3) roose risk stratification for tailoring treatment in atients with NSTE- ACS. In atients with intermediate- to very high-risk NSTE-ACS, routine invasive diagnostics and treatments are recommended. Multivessel coronary disease (MVD), a leading athological foundation of intermediate to very high risk clinical manifestation, accounts for aroximately 3 4% NSTE-ACS cohorts overall and is usually treated with invasive interventions. 4) The American College of Cardiology/American Heart Association guidelines rovide a class IIb recommendation that multivessel ercutaneous coronary intervention (PCI), in contrast to culrit-only PCI, might be reasonable in NSTE-ACS atients undergoing PCI (Level of 774 Coyright 16 The Korean Society of Cardiology

2 Xiaofan Yu, et al. 775 Evidence: B). 3) This recommendation is based on reorts of studies suggesting that multivessel PCI is suerior to culrit vessel only PCI in terms of reeat revascularization. 5-8) However, there is still uncertainty as to whether non-culrit lesions should be treated at the time of culrit-lesion PCI for NSTE-ACS. 3) In the resent study, we sought to examine clinical outcomes of one-time versus staged multivessel stenting in intermediate to very high-risk NSTE- ACS atients with MVD. Subjects and Methods Study oulation Between November 8 and November 12, a total of 147 unselected atients who had undergone a PCI were rosectively registered in the PCI database of General Hosital of Shenyang Military Region. The database contained comrehensive information including clinical and angiograhic characteristics, treatment strategies and clinical outcomes. Eligible atients had at least one intermediate to very high risk criteria with indication for invasive management defined by the 15 Euroean Society of Cardiology (ESC) guidelines for the management of NSTE-ACS 2) ; 3 tyes of very high-risk criteria include recurrent or ongoing chest ain refractory to medical treatment, and recurrent dynamic ST-T wave changes articularly with intermittent ST-elevation and acute heart failure; 3 tyes of high-risk criteria include rise or fall in cardiac troonin comatible with myocardial infarction (MI), dynamic ST- or T-wave changes and Global Registry of Acute Coronary Events (GRACE) score >14; 7 intermediate-risk criteria include diabetes mellitus, renal insufficiency (Estimated glomerular filtration rate [egfr] < 6 ml/min/1.73 m 2 ), left ventricular ejection fraction (LVEF) <4% or congestive heart failure, early ost-infarction angina, rior PCI, rior coronary artery byass graft (CABG) and GRACE risk score>19 and <14. Exclusion criteria were atients who had chronic total occlusion; atients who had rocedural failure (i.e., technical failure), including staged PCI atients who had rocedural failure during the index PCI and scheduled for staging; atients who had cardiac shock, haemodynamic instability, mechanical comlications of MI or malignant ventricular arrhythmia; atients who had renal dialysis or a egfr <3 ml/min/1.73 m 2 ; staged PCI atients who had any major comlication during the index rocedure; atients who had a lanned staged PCI >6 days. Our final oulation included 1531 atients from the database having NSTE-ACS with multivessel PCI (Fig. 1). Treatment All atients were given oral loading doses of asirin (3 mg) 147 atients underwent PCI form Nov 8 to Nov 12 NSTE-ACS n=7252 (6.2%) Multivessel PCI n=249 (33.2%) Intermediate to very high-risk n=1888 (78.4%) Patients included in analysis n=1531 (81.1%) Very high-risk: n=115 High-risk: n=76 Intermediate-risk: n=71 One-time PCI n=859 (54.5%) n=672 (45.5%) 4795 atients with STEMI or stable CAD 4843 atients with single vessel PCI 521 atients with low risk Exclusions: n=357 Chronic total occlusion: n=182 Patients undergoing a staged PCI >6 days: n=21 Renal dialysis or a egfr <3 ml/min/1.73 m 2 : n=5 Cardiac shock, hemodynamically unstable or malignant ventricular arrhythmia: n=17 atients who had any major comlication during the index rocedure: n=23 Mechancical comlications of MI: n=5 Patients who had rocedural failure, including staged PCI atients who had rocedural failure during the index PCI and scheduled for staging: n=14 Fig. 1. Patient flow diagram. PCI: ercutaneous coronary intervention, STEMI: ST-segment elevation myocardial infarction, CAD: coronary artery disease, NSTE-ACS: non ST-segment elevation acute coronary syndromes, egfr: estimated glomerular filtration rate. and cloidogrel (3-6 mg) rior to PCI, unless they had already received antilatelet medication. Interventional rocedures were erformed according to standard techniques and interventional strategies rested on the oerators. The choice between comlete or incomlete revascularization was also at oerators discretion. The culrit lesion was identified by oerators usually based on each atient s electrocardiogram, angiograhic imaging, echocardiogram and, if available, intravascular ultrasound (IVUS) and otical coherence tomograhy (OCT). A lesion was considered a culrit on angiograhy if at least two of the following morhological features suggestive of acute laque ruture were resent: intraluminal filling defects consistent with thrombus, laque ulceration, laque irregularity, dissection or imaired flow. 2)9-11) After the rocedure, the use of asirin lifelong was advised and cloidogrel was rescribed for 12 months. The study was aroved by the hosital ethics committee and all atients gave written informed consent. Follow-u Clinical follow-u was erformed via telehone or at an outatient visit at 3 days, 6 months, and 12 months after the index rocedure and annually until 3 years after the index rocedure. Follow-u angiograhy was recommended to all atients 6 to 12 months after the index rocedure, and reeat revascularization was erformed, if clinically indicated.

3 776 Multivessel PCI in NSTE-ACS Outcomes and definitions The rimary outcome was the incidence of major adverse cardiac events (MACE), defined as the comosite of cardiac death, MI and target vessel revascularization (TVR) during 3-year follow-u. Secondary outcomes included MACE comonents, the comosite of cardiac death or MI, definite/robable stent thrombosis, and any reeat revascularization. MVD was defined as the resence of a significant atherosclerotic coronary artery stenosis ( 7% diameter stenosis) or a 5% stenosis of the left main coronary artery (left main disease) with additional significant stenosis ( 7% diameter stenosis) of at least one other coronary artery assessed visually during coronary angiograhy. 12) is defined as the lanned PCI of non-infarct vessel(s) within 6 days of the index PCI. egfr was calculated from serum creatinine (scr) concentrations using the modified glomerular filtration rate estimating the equation for Chinese atients with chronic kidney disease: egfr (ml/ min/1.73 m 2 )=175 (scr) (age) (.79 if atient is female). 13) Anemia was defined as hemoglobin less than 12 g/dl for men or less than 11 g/dl for women. 14) Early invasive intervention was defined as a coronary angiograhy erformed within 24 h of hosital admission. 2) Delayed invasive intervention was defined as a coronary angiograhy erformed more than 24 h of hosital admission. Technical success was defined as the ability to cross an occluded or stenosed segment and successfully oen the artery (restoration of thrombolysis in myocardial infarction [TIMI] flow grade 3) with a residual stenosis 3% by visual analysis. Cardiac death was defined as death that could not be attributed to a noncardiac etiology. MI was defined as third universal definition of MI resented by The Third Global MI Task Force. 15) TVR was determined as any reeated PCI or CABG to treat a reviously stented vessel. Comlete revascularization was defined when no visually estimated stenosis 5% for the left main and no stenosis 7% for other major arteries and/or their major branches at discharge. Stent thrombosis was classified as definite and robable according to definitions roosed by the Academic Research Consortium. 16) Table 1. Baseline characteristics Unadjusted Proensity score adjusted Characteristic (n=859) (n=672) (n=4) (n=4) Age (years) 62.7± ± ± ±1..77 Gender (male) 58 (67.5) 496 (73.8).8 3 (71.4) 36 (72.9).644 BMI (kg/m 2 ) 25.2± ± ± ± Heart rate (bm) 73.8± ± ± ± Atrial fibrillation, n (%) 21 (2.4) (3.) (2.1) 1 (2.4).816 Risk factors, n (%) Anemia 76 (8.8) 58 (8.6) (7.1) 33 (7.9).694 Diabetes 38 (35.9) 256 (38.1) (37.9) 159 (37.9) 1. Hyertension 561 (65.3) 454 (67.6) (66.9) 279 (66.4).884 Hyerliidemia 384 (44.7) 33 (49.1).86 3 (48.3) 197 (46.9).679 PAD 24 (2.8) 19 (2.8) (3.1) 12 (2.9).839 Current smoker 382(44.5) 341 (5.7) (5.7) 21 (5.).836 Previous MI 172 (.) 191 (28.4) <.1 15 (25.) 113 (26.9).529 Previous PCI 3 (23.6) 167 (24.9) (26.) 115 (27.4).64 Previous CVD 68 (7.9) 67 (1.) (1.) 4 (9.5).816 Tye of NSTE-ACS, n (%) UA 645 (75.1) 492 (73.2) 36 (72.9) 31 (73.8) NSTEMI 214 (24.9) 18 (26.8) 114 (27.1) 15 (26.2) egfr 6 ml/min/1.73 m 2, n (%) 88 (1.2) 78 (11.6) (1.7) 38 (9.).418 LVEF 4%, n (%) 13 (1.5) 14 (2.1).4 9 (2.1) 7 (1.7).614 BMI: body mass index, PAD: eriheral arterial disease, MI: myocardial infarction, PCI: ercutaneous coronary intervention, CVD: cerebrovascular disease, Hb: hemoglobin, NSTE-ACS: non ST-segment elevation acute coronary syndromes, UA: unstable angina, NSTEMI: non-st-segment elevation myocardial infarction, egfr: estimated glomerular filtration rate, LVEF: Left ventricular ejection fraction

4 Xiaofan Yu, et al. 777 Table 2. Treatment and rocedure related characteristics Unadjusted Proensity score adjusted Characteristic (n=859) (n=672) (n=4) (n=4) Timing of invasive strategy, n (%) Early PCI 374 (43.5) 43 (4.) 181 (43.1) 167 (39.8) Delayed PCI 485 (56.5) 269 (6.) 239 (56.9) 253 (6.2) Disease extent, n (%) < vessel disease 493 (57.4) 211 (31.4) 171(4.7) 175 (41.7) 3-vessel disease 366 (42.6) 461 (68.6) 249 (59.3) 245 (58.3) Left main disease disease, n (%) 92 (1.7) 74 (11.) (9.8) 45 (1.7).649 Temorary acemaker used, n (%) 4 (.5) 5 (.7) (.7) 4 (1.).74 IVUS used, n (%) 28 (3.3) 12 (1.8) (2.6) 9 (2.1).651 OCT used, n (%) 3 (.3) 1 (.2) (.5) 1 (.2).563 Stent numbers er atient 3 (2-3) 4 (3-5) <.1 3 (3-4) 3 (3-4).5 Total stent length (mm) 7 (54-94) 115 (85-145) <.1 9 (69-1) 93 (72-122).374 Comlete revascularization, n (%) 575 (66.9) 41 (61.) (6.) 256 (61.).778 Contrast volume (ml) Initial rocedure (-3) (15-2) <.1 25 (-3) (14-) <.1 Staged rocedure - (15-26) - - (14-23) - Total (-3) 4 (31-5) <.1 25 (-3) 4(39-47) <.1 Length of hosital (days) 6 (4-8) 1 (8-14) <.1 6 (5-8) 1 (8-14) <.1 Medications at discharge, n (%) Asirin 847 (98.6) 665 (99.) (98.1) 414 (98.6).59 Cloidogrel 857 (99.8) 67 (99.7) (99.8) 419 (99.8) 1. ACE inhibitor/arb 595 (69.3) 483 (71.9) (68.3) 32 (71.9).258 β-blockers 685 (79.7) 54 (8.4) (79.3) 335 (79.8).864 Statins 79 (82.5) 573 (85.3) (82.9) 361 (86.).216 Calcium blocker 11 (11.8) 79 (11.8) (12.1) 45 (1.7).515 DAPT duration (days) Less than (4.8) 28 (4.2) 23 (5.5) 18 (4.3) From 18 to (1.9) 57 (8.5) 42 (1.) 31 (7.4) More than (84.3) 587 (87.4) 355 (84.5) 371 (88.3) Values are resented as numbers and ercentage. PCI: ercutaneous coronary intervention, IVUS: intravascular ultrasound, OCT: otical coherence tomograhy, ACE: angiotensin-converting enzyme, ARB: angiotensin II recetor blocker, DAPT: dual antilatelet theray Statistical analysis Continuous variables were exressed as mean±standard deviation (SD), and categorical variables were exressed as number and/or ercentages. For grou comarisons, Pearson chi-square test or Fisher s exact test was used for categorical variables. Student s unaired t-test or the Mann-Whitney rank-sum test, as aroriate, was used for continuous variables. To minimize the influence of confounders on outcome, we used roensity score matching analysis. Patients who underwent staged PCI were matched in a 1:1 ratio with atients who underwent a onetime PCI using the nearest neighbor matching, which were based on all available variables listed in Tables 1 and 2 excet GRACE Score, IVUS used, OCT used, contrast volume, length of hosital, medication at discharge and dual antilatelet theray (DAPT) duration. A difference of <1% was regarded as accetable. Time to event data with estimated event rates calculated by Kalan

5 778 Multivessel PCI in NSTE-ACS Meier method were comared with the log-rank test. In addition, we erformed Kalan-Meier analyses at the landmark eriods of to 9 days and 9 days to 3 years to evaluate the effect of revascularization strategy on clinical outcomes at different time eriods. All statistical tests were 2-tailed, and statistical analyses were erformed with SPSS Ver. software (SPSS Inc., Chicago, IL, USA). Results Patients and treatments One-time PCI was erformed in 56.1% (859/1531), and the remaining 43.9% (672/1531) had staged PCI (Of these, 8.7% [542/672] had staged non-culrit intervention during the same hositalization and 19.3% [13/672] had lanned staged nonculrit rocedures after hosital discharge). The median delay of the staged PCI was 5 days (interquartile rang [IQR], 3-9 days). As noted in Tables 1 and 2, male, revious MI, trile-vessel disease, and current smoking were associated with more staging. The volume of contrast media utilized during the index rocedure in the staged PCI grou was smaller ( ml [IQR, 15-2 ml] vs. ml [IQR, -3 ml], <.1) though the total volume utilized in the initial rocedure lus staged rocedure was greater (4 ml [IQR, 31-5 ml] vs. ml [IQR, -3 ml], <.1). Medications at discharge were similar between both grous. Most atients took dual antilatelet theray (DAPT), which was consistent with the standard recommendation. After roensity matching, there were no statistically significant differences in reselected variables between the two grous. Clinical outcomes of unadjusted oulations As noted in Table 3, Fig. 2A and Fig. 3A, MACE occurred in 132 atients (.8%) in the staged grou and 162 atients (19.7%) in the one-time grou during 3-year follow-u (=.68). Rates of each comonent of 3-year cumulative MACE were similar between both grous. The estimated 3-year comosite rate of cardiac death or MI was 7.1% in the staged PCI grou comared with 9.1% in Table 3. 9-day and 3-year outcomes for unadjusted and adjusted oulations Unadjusted Proensity score adjusted Outcomes (n=859) (n=672) (n=4) (n=4) 9 days, n (%) MACE 22 (2.6) 13 (1.9) (3.3) 5 (1.2).37 Cardiac death or MI 18 (2.1) 8 (1.2) (2.6) 3 (.7).31 Cardiac death 6 (.7) 5 (.7) (.7) 1 (.2).318 MI 16 (1.9) 7 (1.).19 9 (2.1) 3 (.7).81 TVR 12 (1.4) 7 (1.1) (1.7) 4 (1.).361 Any revascularization 18 (2.1) 15 (2.3) (2.1) 6 (1.4).432 Definite/robable ST 11 (1.3) 4 (.6) (1.4) 3 (.7) years, n (%) MACE 162 (19.7) 132 (.8) (21.8) 74 (18.9).249 Cardiac death or MI 74 (9.1) 43 (7.1) (11.1) 26 (7.).33 Cardiac death 41 (5.1) 24 (4.) (4.8) 9 (2.5).67 MI 47 (5.8) 28 (4.5).26 3 (7.7) (5.).162 TVR 113(13.9) 18 (17.3) (14.5) 58 (14.9).971 Any revascularization 151 (18.6) 141 (22.3) (.4) 8 (.3).888 Definite/robable ST 16 (1.9) 8 (1.3) (2.2) 5 (1.2).28 Acute (<24 h) 5 (.6) 1 (.1) (1.) 1 (.2).178 Subacute (1-3 d) 5 (.6) 3 (.4).78 2 (.5) 2 (.5).99 Late (>3 d) 6 (.8) 4 (.7).86 3 (.8) 2 (.5).651 Values are resented as numbers and ercentage. MACE: major adverse cardiac events, MI: myocardial infarction, TVR: target vessel revascularization, ST: stent thrombosis

6 Xiaofan Yu, et al. 779 Major adverse cardiac events (%) Log-rank =.68 3 Log-rank = Major adverse cardiac events (%) A Patients at risk Follow-u duration (days) One-time Staged Major adverse cardiac events (%) Patients at risk One-time Staged Log-rank = Log-rank = Follow-u duration (days) Follow-u duration (days) Follow-u duration (days) C D Fig. 2. Kalan-Meier assessment of MACE for unadjusted (A) and roensity score matched (B) atients; 9-day landmark analysis of MACE for unadjusted (C) and roensity score matched (D) atients. MACE: major adverse cardiac events, PCI: ercutaneous coronary intervention. B Major adverse cardiac events (%) Log-rank = Log-rank = the one-time PCI grou (=.129). In addition, no significant differences in the 3-year rates of any revascularization (22.3% vs. 18.6%, =.83) and definite/robable stent thrombosis (1.3% vs. 1.9%, =.295) were observed. At the 9-day landmark analysis (Tables 3 and 4, Fig. 2C and Fig. 3C), no significant differences in terms of MACE, its individual comonents, any revascularization and definite/robable stent thrombosis were observed at the landmark eriod of to 9 days and 9 days to 3 years. Clinical outcomes of roensity score-matched oulations After generating a roensity score, 4 of the 672 atients who underwent staged PCI were matched with a atient, resectively, who underwent a one-time PCI. There were no differences in reselected variables for the roensity matched subjects (Table 1, 2). As noted in Table 3, Fig. 2B and Fig. 3B, at 3 years, there were no differences in MACE (18.9% vs. 21.8%, =.249); whereas there was a significantly lower incidence of cardiac death or MI (7.% vs. 11.1%, =.33). The risk for cardiac death in the staged PCI grou tended to be lower (2.5% vs. 4.8%, =.67). Other clinical outcomes including MI (5.% vs. 7.7%, =.162), TVR (14.9% vs. 14.5%, =.971), any revascularization (.3% vs..4%, =.888), and definite/robable stent thrombosis (1.2% vs. 2.2%, =.28) were not significantly different between the two study grous. The results of the 9-day landmark analysis for roensity score matched atients were shown in Tables 3 and 4, Fig. 2D and Fig. 3D.

7 78 Multivessel PCI in NSTE-ACS Cardiac death or myocardial infarction (%) Log-rank = Cardiac death or myocardial infarction (%) Log-rank = A Follow-u duration (days) Patients at risk One-time Staged B Follow-u duration (days) Cardiac death or myocardial infarction (%) Log-rank = Log-rank = Cardiac death or myocardial infarction (%) Log-rank = Log-rank = C Patients at risk Follow-u duration (days) One-time Staged D Follow-u duration (days) Fig. 3. Kalan-Meier assessment for the comosite of cardiac death or MI for unadjusted (A) and roensity score matched(b) atients; 9-day landmark analysis of the comosite of cardiac death or MI for unadjusted (C) and roensity score matched (D) atients. PCI: ercutaneous coronary intervention. MI: myocardial infarction. Table 4. Clinical outcomes from 9 days to 3 years after index PCI Outcomes Unadjusted Proensity score adjusted Between 9 days and 3 years MACE 14/837 (17.6) 119/655 (19.3) /46 (19.1) 69/413 (17.9).641 Cardiac death or MI 56/841 (7.1) 35/66 (6.) /49 (8.7) 23/415 (6.3).191 Cardiac death 35/853 (4.4) 19/663 (3.2).23 16/417 (4.1) 8/417 (2.2).117 MI 31/841 (4.) 21/66 (3.5) /49 (5.6) 17/415 (4.6).531 TVR 11/841 (12.7) 11/656 (16.4).58 51/41 (13.1) 54/413 (14.).797 Any revascularization 133/835 (16.9) 126/648 (.5).76 72/48 (18.6) 74/411 (19.1).917 Definite/robable ST 5/841 (.6) 4/66 (.7).971 3/49 (.8) 2/415 (.5).651 PCI: ercutaneous coronary intervention, MACE: major adverse cardiac events, MI: myocardial infarction, TVR: target vessel revascularization, ST: stent thrombosis

8 Xiaofan Yu, et al. 781 The staged PCI grou showed a lower 9-day incidence of MACE (1.2% vs. 3.3%, =.37), mainly due to a lower comosite rate of cardiac death or MI (.7% vs. 2.6%, =.31). The 9-day rates of MI did not differ significantly between the 2 study grous, but it resented a trend in favor of staged PCI (.7% vs. 2.1%, =.81). For the 9-day to 3-year follow-u eriod, both the incidences of MACE (17.9% vs. 19.1%, =.641) and the comosite of cardiac death or MI (6.3% vs. 8.7%, =.191) were similar between the two grous. Cardiac death, TVR, any revascularization and definite/robable stent thrombosis did not differ significangtly between the two grous at the landmark eriod of to 9 days and 9 days to 3 years. Discussion To our knowledge, this is the first study to examine the efficacy of staged versus one-time aroach in intermediate to very highrisk NSTE-ACS atients with multivessel PCI. Main findings of this study were as follow: in intermediate to very high-risk NSTE-ACS atients with multivessel disease, staged PCI was associated with a lower comosite rate of cardiac death or MI comared with onetime PCI strategy. This benefit of staged PCI was more aarent in the early eriod after rocedures, rather than middle-late eriod. Clinicians are often faced with the decision of whether to treat the nonculrit lesions during the index rocedure or to treat it at a later time. 17) Hannan et al. comared the one-time comlete revascularization in the index admission versus PCI of the culrit lesion only with staged non-culrit PCI for comlete revascularization in a subsequent admission among atients with NSTE-ACS and MVD. 18) At 3 years, no significant difference in allcause mortality was observed between the two grous. However, the staged PCI grou did not include the atients who underwent a staged intervention during the same hositalization. Furthermore, it is yet unknown whether it was different in all-cause mortality between the two grous after exclusions of low risk atients. In the current observational study, the sueriority of staged PCI strategy over one-time PCI strategy in terms of the comosite of cardiac death or MI was resented, esecially in the early eriod after PCI. There are some otential itfalls of one-time multivessel PCI aroach. First, NSTE-ACS atients are in a heightened thrombotic and inflammatory state ) One-time multivessel PCI can lead to rolongation of rocedure time, exosure to a higher radiation dose 23) and larger volume of contrast agents during the index rocedure comared to staged revascularization. This may result in an increased number of comlications such as erirocedural MI or acute kidney injury as well as stent thrombosis. 24)25) Moreover, atients with high/intermediate risks of NSTE-ACS are often in a oor clinical state or have concomitant comorbidities. PCI on the culrit lesion first and staged non-culrit PCI at a later date with otimal medical theray usually results in the atient being stable and also allows clinicians to reassess the atient s clinical and angiograhic states. Risk stratification is essential for the clinical decision-making rocess in NSTE-ACS atients. With resect to outcomes, erirocedural comlications of intervention, as well as the long-term ischemic risk, remain higher in high/intermediate risk NSTE-ACS than in lowrisk NSTE-ACS atients. 26-3) When choosing the otimal treatment strategy in the individual atient with NSTE-ACS and MVD, general atient condition and concomitant comorbidities have to be taken into account. However, the otimal strategy for the management of NSTE-ACS atients with oor clinical resentation and multivessel disease has not been well established. Therefore, our atient inclusion criteria, which were based on ESC guidelines, selected NSTE-ACS atients with intermediate- to very high-risk features. Our study had several limitations. First, this was a retrosective analysis from a rosective single center registry. The decisions for one-time vs. staged PCI were not based on a randomization but at hysicians discretion, which resulted in obvious confounding and selection bias. Although we analyzed by adjusting many ossible confounding factors, unmeasured confounding or selection bias might have influenced our findings. Second, in this study, all atients underwent PCI in the setting of antilatelet theray with cloidogrel. When the new antilatelet agent ticagrelor is available, this finding deserves further investigation. Third, the relatively high frequency of angiograhy during the eriod between 6 to 12 months after the rocedure could bias the MACE, esecially TVR. However, this bias was limited, because the two grous had similar frequencies of follow-u angiograhy and because reeat intervention was guided by either recurrent angina or signs of ischemia that had rogressed angiograhically, even without angina based on invasive or noninvasive testing. Fourth, our data were collected before current ractice guidelines 2) were ublished. Therefore, timing of invasive strategies were not run according to current guidelines. Fifth, given the low absolute number of events at 9-day follow u in the roensity score matched cohort, our study was not owered to detect significant differences in cardiac death, MI, TVR and stent thrombosis at 9 days. Last, considering follow-u angiograhy and routine cardiac biomarkers surveillance was not mandatory, therefore the incidence of MI might have been underestimated. Conclusion In intermediate to very high-risk NSTE-ACS atients with multivessel disease, staged PCI is suerior to one-time PCI in

9 782 Multivessel PCI in NSTE-ACS terms of the comosite of cardiac death or MI. Our findings require further confirmation by randomized trial. References 1. Task Force members, Windecker S, Kolh P, et al. 14 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the Euroean Society of Cardiology (ESC) and the Euroean Association for Cardio-Thoracic Surgery (EACTS) Develoed with the secial contribution of the Euroean Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 14;35: Roffi M, Patrono C, Collet JP, et al. 15 ESC Guidelines for the management of acute coronary syndromes in atients resenting without ersistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the Euroean Society of Cardiology (ESC). Eur Heart J 16;37: Amsterdam EA, Wenger NK, Brindis RG, et al. 14 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a reort of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 14;64:e Loscalzo J, Longo DL, Fauci AS, et al. Unstable angina and non-stelevation myocardial infarction. In: Cannon CP, editor. Harrison Cardiovascular Medicine. New York: McGraw-Hill Education; Shishehbor MH, Lauer MS, Singh IM, et al. In unstable angina or non-st-segment acute coronary syndrome, should atients with multivessel coronary artery disease undergo multivessel or culritonly stenting? J Am Coll Cardiol 7;49: Kim MC, Jeong MH, Ahn Y, et al. What is otimal revascularization strategy in atients with multivessel coronary artery disease in non- ST-elevation myocardial infarction? Multivessel or culrit-only revascularization. Int J Cardiol 11;153: Brener SJ, Milford-Beland S, Roe MT, et al. Culrit-only or multivessel revascularization in atients with acute coronary syndromes: an American College of Cardiology National Cardiovascular Database Registry reort. Am Heart J 8;155: Zaata GO, Lasave LI, Kozak F, et al. Culrit-only or multivessel ercutaneous coronary stenting in atients with non-st-segment elevation acute coronary syndromes: one-year follow-u. J Interv Cardiol 9;22: Ambrose JA, Winters SL, Stern A, et al. Angiograhic morhology and the athogenesis of unstable angina ectoris. J Am Coll Cardiol 1985;5: Kerensky RA, Wade M, Deedwania P, Boden WE, Peine CJ. Revisiting the culrit lesion in non-q-wave myocardial infarction. Results from the VANQWISH trial angiograhic core laboratory. J Am Coll Cardiol 2;39: Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O Neill WW. Multile comlex coronary laques in atients with acute myocardial infarction. N Engl J Med ;343: Luczak D, Majda W, Dabrowski R, et al. Prognostic imortance of the extent of coronary revascularisation in atients with acute coronary syndromes and multivessel disease: one-year rosective follow-u. Kardiol Pol 15;73: Ma YC, Zuo L, Chen JH, et al. Modified glomerular filtration rate estimating equation for Chinese atients with chronic kidney disease. J Am Soc Nehrol 6;17: XH W, XF L. Diagnostics. 8th ed. Beijing: Peole s Medical Publishing House; Thygesen K, Alert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 12;6: Cutli DE, Windecker S, Mehran R, et al. Clinical end oints in coronary stent trials: a case for standardized definitions. Circulation 7;115: Dangas GD, George JC, Weintraub W, Poma JJ. Timing of staged ercutaneous coronary intervention in multivessel coronary artery disease. JACC Cardiovasc Interv 1;3: Hannan EL, Samadashvili Z, Walford G, et al. Staged versus one-time comlete revascularization with ercutaneous coronary intervention for multivessel coronary artery disease atients without ST-elevation myocardial infarction. Circ Cardiovasc Interv 13;6: Ohashi Y, Kawashima S, Mori T, et al. Soluble CD4 ligand and interleukin-6 in the coronary circulation after acute myocardial infarction. Int J Cardiol 6;112: Kereiakes DJ, Gurbel PA. Peri-rocedural latelet function and latelet inhibition in ercutaneous coronary intervention. JACC Cardiovasc Interv 8;1: Chan MY, Andreotti F, Becker RC. Hyercoagulable states in cardiovascular disease. Circulation 8;118: Brummel-Ziedins K, Undas A, Orfeo T, et al. Thrombin generation in acute coronary syndrome and stable coronary artery disease: deendence on lasma factor comosition. J Thromb Haemost 8;6: Di Mario C, Mara S, Flavio A, et al. Single vs multivessel treatment during rimary angiolasty: results of the multicentre randomised HEacoat for culprit or multivessel stenting for Acute Myocardial Infarction (HELP AMI) Study. Int J Cardiovasc Intervent 4;6: Gasior P, Deserak P, Gierlaszynska K, et al. Percutaneous coronary intervention in treatment of multivessel coronary artery disease in atients with non-st-segment elevation acute coronary syndrome.

10 Xiaofan Yu, et al. 783 Postey Kardiol Interwencyjnej 13;9: Zimarino M, Curzen N, Cicchitti V, De Caterina R. The adequacy of myocardial revascularization in atients with multivessel coronary artery disease. Int J Cardiol 13;168: Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in ost-myocardial infarction atients: nationwide real world data demonstrate the imortance of a longterm ersective. Eur Heart J 15;36: Marso SP, McGuire DK. Coronary revascularization strategies in atients with diabetes and multivessel coronary artery disease: has the final chater been written? J Am Coll Cardiol 14;64: Elbarouni B, Ismaeil N, Yan RT, et al. Temoral changes in the management and outcome of Canadian diabetic atients hositalized for non-st-elevation acute coronary syndromes. Am Heart J 11;162: e Abu-Assi E, Ferreira-Gonzalez I, Ribera A, et al. Do GRACE (Global Registry of Acute Coronary events) risk scores still maintain their erformance for redicting mortality in the era of contemorary management of acute coronary syndromes?. Am Heart J 1;16: e Reuter PG, Rouchy C, Cattan S, et al. Early invasive strategy in highrisk acute coronary syndrome without ST-segment elevation. The Sisca randomized trial. Int J Cardiol 15;182:414-8.