International Journal of Cardiology 172 (2014) 76–81

Contents lists available at ScienceDirect

International Journal of Cardiology

j ourna l homepage: www.e lsev ie r .com/ locate / i j ca rd

Acute multivessel revascularization improves 1-year outcome inST-elevation myocardial infarction

A nationwide study cohort from the AMIS Plus registry

Raban Jeger a,1, Milosz Jaguszewski b,1, Brahmajee N. Nallamothu c, Thomas F. Lüscher b, Philip Urban d,Giovanni B. Pedrazzini e, Paul Erne f,g,⁎, Dragana Radovanovic g, for the AMIS Plus Investigatorsa Cardiology, University Hospital, Basel, Switzerlandb University Heart Center, University Hospital Zurich, Switzerlandc Division of Cardiovascular Diseases, University of Michigan, Ann Arbor, USAd Cardiovascular Department, Hôpital de La Tour, Geneva, Switzerlande Cardiology, CardioCentro Ticino, Lugano, Switzerlandf Cardiology, Luzerner Kantonsspital, Lucerne, Switzerlandg AMIS Plus Data Center, Institute of Social and Preventive Medicine, University of Zurich, Switzerland

⁎ Corresponding author at: AMIS Plus Data Center, HirscSwitzerland.

E-mail address: paul.erne@erne-net.ch (P. Erne).1 These authors contributed equally to this work.

0167-5273/$ – see front matter © 2014 Elsevier Ireland Lhttp://dx.doi.org/10.1016/j.ijcard.2013.12.083

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 17 July 2013Received in revised form 26 November 2013Accepted 20 December 2013Available online 4 January 2014

Keywords:Complete revascularizationDrug eluting stentsMulti-vessel diseaseSTEMI

Background: The optimal strategy for percutaneous coronary intervention (PCI) of ST-segment elevationmyocar-dial infarction (STEMI) inmulti-vessel disease (MVD), i.e., multi-vessel PCI (MV-PCI) vs. PCI of the infarct-relatedartery only (IRA-PCI), still remains unknown.Methods: Patients of the AMIS Plus registry admitted with an acute coronary syndrome were contacted after amedian of 378 days (interquartile range 371–409). The primary end-point was all-cause death. The secondaryend-point included all major adverse cardiovascular and cerebrovascular events (MACCE) including death, re-infarction, re-hospitalization for cardiac causes, any cardiac re-intervention, and stroke.Results: Between 2005 and 2012, 8330 STEMI patients were identified, of whom 1909 (24%) had MVD. Of these,442 (23%) received MV-PCI and 1467 (77%) IRA-PCI. While all-cause mortality was similar in both groups (2.7%both, p N 0.99), MACCE was significantly lower after MV-PCI vs. IRA-PCI (15.6% vs. 20.0%, p = 0.038), mainly

driven by lower rates of cardiac re-hospitalization and cardiac re-intervention. Patients undergoing MV-PCIwith drug-eluting stents had lower rates of all-cause mortality (2.1% vs. 7.4%, p = 0.026) and MACCE (14.1%vs. 25.9%, p = 0.042) compared with those receiving bare metal stents (BMS). In multivariate analysis, MV-PCI(odds ratio, OR 0.69, 95% CI 0.51–0.93, p = 0.017) and comorbidities (Charlson index ≥ 2; OR 1.42, 95% CI1.05–1.92, p = 0.025) were independent predictors for 1-year MACCE.Conclusion: In an unselected nationwide real-world cohort, an approach using immediate complete revasculari-zationmay be beneficial in STEMI patients withMVD regardingMACCE, specificallywhen drug-eluting stents areused, but not regarding mortality. This has to be tested in a randomized controlled trial.

© 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Primary percutaneous coronary intervention (PCI) is the preferredtreatment strategy for restoring myocardial reperfusion in patientswith ST-segment elevation myocardial infarction (STEMI) [1] becauseit improves outcome [2]. In STEMI patients, multi-vessel disease(MVD) as compared to single-vessel disease (SVD) relates to a worseprognosis and is documented in up to half of the patients referred forurgent angiography [3,4]. However, the long-term benefit of acutemultivessel revascularization comprising both the culprit vessel,

hengraben 84, CH-8001 Zurich,

td. All rights reserved.

i.e., the infarct related artery (IRA), and the non-infarct related arteriesis still controversial. Multi-vessel PCI for additional non-IRA lesions(MV-PCI) rather than PCI of the IRA only (IRA-PCI) has not been evalu-ated appropriately in large randomized clinical trials [5]. Therefore, dueto lacking data, the Task Forces for PCI of the European Society ofCardiology (ESC) and the American College of Cardiology/AmericanHeart Association (ACC/AHA) recommend IRA-PCI in the acute courseof STEMI [5,6], with acute complete revascularization being recom-mended in patients with cardiogenic shock only [5].

To better understand whether patients with STEMI and MVD ina “real-world setting” are more likely to benefit from MV-PCI vs.IRA-PCI, data from the Swiss nationwide Acute Myocardial Infarctionin Switzerland (AMIS) Plus Registry have previously been analyzeddocumenting a higher prevalence of MV-PCI in high-risk patients,which was not associated with higher in-hospital mortality after

77R. Jeger et al. / International Journal of Cardiology 172 (2014) 76–81

stratifying patients based on their risk [7]. However, no long-termfollow-up was available at that time, leaving uncertainty about thedownstream effects of this approach [7]. Since then follow-up datahave been collected in a large percentage of the registry patients. There-fore, the purpose of the studywas to assess whether MV-PCI vs. IRA-PCIin patients with STEMI and MVD influences 1-year outcome.

2. Methods

2.1. Study design

The AMIS Plus project started in January 1997 as a large, nationwide prospectiveregistry of patients admitted with acute coronary syndromes to hospitals in Switzerland,and has so far collected data from more than 40,000 patients. The design of the registryhas been described previously [8,9]. All participating centers, ranging from community in-stitutions to large tertiary facilities, provide blinded data that are subsequently centralizedat the AMIS Plus Data Center. All data are entered in internet- or on paper-based question-naires by the local investigators and subsequently checked for plausibility and consistencyby the AMIS Plus Data Center at the Institute of Social and Preventive Medicine of theUniversity of Zurich. The registry was approved by the Over-Regional Ethics Committeefor Clinical Studies, the Swiss Board for Data Security, and all Cantonal Ethic Committees.

2.2. Data collection

The AMIS Plus Registry collects 230 items including medical history, co-morbidities,known cardiovascular risk factors (dyslipidemia, arterial hypertension, diabetes, obesityand smoking), clinical presentation, out-of-hospital management, early in-hospital man-agement, reperfusion therapy, hospital course, diagnostic tests used or planned, lengthof stay, discharge medication and discharge destination, immediate drug treatment anddischarge medication [8]. The co-morbidities are assessed using the Charlson Index [8].Patients are enrolled in the registry based on their final diagnosis. The post-dischargefollow-up for the primary and secondary endpoints was obtained directly by telephonecalls using a detailed and standardized questionnaire.

2.3. Definitions

STEMIwas defined by characteristic symptomswith specific ECG changes and cardiacmarker elevation (creatine kinase MB fraction at least twice the upper limit of normal ortroponin I or T above individual hospital cut-off levels). All patients required ST-segmentelevation and/or the new development of left bundle branch block on the initial ECG atpresentation. MVD was defined as a presence of angiographic stenosis of ≥50% in atleast 2 different main epicardial coronary arteries and/or involving the left main. MV-PCIwas defined as an acute primary PCI in at least 2 of 3 main coronary arteries performedat baseline. Lesions involving the left main that were subsequently treated were consid-ered a separate lesion from those involving the left anterior descending and circumflexcoronary arteries. Thedecision regardingMV-PCI or IRA-PCIwas at the treatingphysician'sdiscretion.

2.4. Study endpoints

The primary end-point of the study was 1-year all-cause mortality. The secondaryend-point contained all major adverse cardiovascular and cerebrovascular events(MACCE) defined as a composite of all-cause death, re-infarction, any cardiac re-intervention (such as coronary angiography, PCI, coronary artery bypass graft sur-gery, ablation, pacemaker or implantable cardioverter defibrillator implantation),and re-hospitalization due to any cardiovascular diagnosis defined as a hospitaliza-tion of at least one night for cardiovascular reasons including all bleeding, resistantangina pectoris, circulatory collapse, arrhythmias, adverse reaction to cardiovascularmedication, and stroke.

2.5. Statistical analysis

The results are presented as percentages for categorical variables and analyzed usingthe non-parametric Pearson x2 test or Fisher's exact test as appropriate. Continuousnormally distributed variables are expressed as means ± standard deviation (SD) andcompared using the Student's unpaired t-test. Continuous non-normally distributedvariables are expressed as median and interquartile ranges and analyzed using theMann–WhitneyU test. All statistical testswere 2-tailed. A p-value of b0.05was consideredstatistically significant. The end-points that occurred during the middle-term follow-upwere counted and compared for both groups. Multivariate logistic regression was usedto examine predictors for the 1-year composed end-point and included the followingvariables:MV-PCI, age, sex, left main involvement, Killip class N 2, Charlson comorbiditiesindex ≥ 2 and out-of-hospital resuscitation which was used in a previous study [7]. SPSSsoftware (version 19, SPSS Inc., Chicago, Illinois, USA) was used for all statistical analyses.

3. Results

3.1. Patients

Between January 2005 and June 2012, 8330 patients with STEMIundergoing urgent PCI were enrolled in the AMIS Plus database. Thepresent analysis included patients with known coronary anatomy(n = 7919), MVD documented during coronary angiography at thetime of STEMI (n = 2486), written informed consent (n = 2070),and with follow-up data available (n = 1909, 77% of patients withMVD; Fig. 1). Of these, 442 (23%) received MV-PCI and 1467 (77%)IRA-PCI.

3.2. Baseline characteristics

Baseline characteristics are presented in Table 1. In general, patientsundergoing MV-PCI had a similar prevalence of cardiovascular risk fac-tors and history of coronary artery disease and heart failure as patientswith IRA-PCI. PatientswhounderwentMV-PCI less frequently had a his-tory of cerebrovascular disease comparedwith patientswhounderwentIRA-PCI (2.3% vs. 4.8%, p = 0.021) but they presented more frequentlywith Killip class III or IV (5.5% vs. 2.9%, p = 0.017). In addition, bothgroups were treated similarly at discharge regarding antiplatelet thera-py, betablockers, inhibitors of ACE, and angiotensin-receptor blockers(Table 2). However, there was a non-significant trend towards lowerstatin prescription among patients who underwent MV-PCI comparedwith those who underwent IRA-PCI (97.0% vs. 98.4%, p = 0.07).

3.3. Overall outcomes

The median follow-up duration for the overall population was378 days (interquartile range, IQR 371–409), with no differencesbetween both groups (MV-PCI vs. IRA-PCI: 387 [IQR 371–409] vs. 388days [IQR 372–410], p = 0.35). All-cause mortality was similar inboth groups (2.7% both, p N 0.99). However, rates of MACCE were sig-nificantly lower in patients with MV-PCI than in patients with IRA-PCI(15.6% vs. 20.0%, p = 0.038, Table 3). While there were no differencesregarding re-infarction (4.6% vs. 3.7%, p = 0.39) and stroke (0.2% vs.0.6%, p = 0.69), patients who underwent MV-PCI as compared tothose who underwent IRA-PCI were less frequently re-hospitalizeddue to any cardiovascular cause (24.3% vs. 29.3%, p = 0.044) and lessfrequently referred for any coronary angiography/intervention (10.6%vs. 15.3%, p = 0.016). Of all patients who underwent initial MV-PCI,47 had a cardiac re-intervention during the follow-up period, of which21 (45%) were planned PCI and 12 (26%) were urgent PCI (14 other in-terventions). In contrast, of all patients undergoing IRA-PCI, 224 had acardiac re-intervention during the follow-up period, of which 101(45%, p = 1.00) were planned PCI and 42 (19%, p = 0.32) were urgentPCI (81 other interventions). Rates of planned revascularizations werenot different between the groups (4.8% vs. 6.9%, p = 0.12).

After stratifying patients by stent type, patients undergoing MV-PCIand receiving drug-eluting stents (DES) had better outcomes ascompared with those receiving bare metal stents (BMS) in terms ofall-cause mortality (2.1% vs. 7.4%, p = 0.026) and overall MACCE(14.1% vs. 25.9%, p = 0.042, see Table 4). The benefit was sustainedup to 2.28 years of follow-up.

In multivariate regression analysis, MV-PCI and comorbidities(Charlson Index ≥ 2) were identified as independent predictors ofMACCE (odds ratio, OR 0.69, 95% confidence interval, CI 0.51–0.93,p = 0.017; OR 1.42, 95% CI 1.05–1.92, p = 0.025, respectively, Table 5).

4. Discussion

In this large nationwide all-comer registry, acute multivessel coro-nary revascularization in patients with STEMI and MVDwas not associ-ated with higher mortality during 1-year follow-up. Instead, MV-PCI

Fig. 1. Flow chart of the study design.

78 R. Jeger et al. / International Journal of Cardiology 172 (2014) 76–81

compared with IRA-PCI resulted in a significant reduction of the com-posite end-point mainly owing to fewer cardiac re-hospitalizationsand cardiac re-interventions. Moreover, MV-PCI, besides comorbidities,was recognized as an independent predictor of middle-term outcome.Finally, after stratifying for stent type, a strategy of MV-PCI using DESsignificantly improved both mortality and overall MACCE when com-pared to MV-PCI using BMS.

Primary PCI to treat STEMI has been clearly shown to improve out-comes [5]. MVD encountered during urgent angiography due to STEMIremains a challenging dilemma [3,10–13]. Patients with STEMI andMVD are likely to have adverse prognoses due to the increased cardio-vascular morbidity and mortality [12,14–15], have a higher incidenceof recurrent revascularization [14], and are more likely to presentlower left ventricular ejection fraction compared to those with singlevessel disease [16]. Moreover, acute myocardial infarction can impaircoronary flow globally mainly caused by the increased systemic inflam-matory response and vasospasm [17–19]. Therefore, immediate com-plete revascularization during the acute course of STEMI is stilldebated [20]. Several studies reported, however, that MV-PCI duringthe course of STEMI appears to be associated with increased mortality,overall cardiovascular adverse events, and stent thrombosis [4,21–25].Also, one of the largest analyses from the National Cardiovascular DataRegistry suggested no benefit from immediate complete revasculariza-tion, even in patients with cardiogenic shock [26].

Previously published data of the AMIS Plus Registry showed higherin-hospital event rates after MV-PCI as compared with IRA-PCI [7].However, those differences disappeared after stratifying patientsbased on risk [7]. In contrast, the present analysis comprising 1-yearfollow-up data documented a significantly better outcome in the

long run in patients with MV-PCI owing essentially to lower re-hospitalization and re-intervention rates. These results are in concor-dance with prior data published by Qarawani et al., where MV-PCIwas supported as feasible and safe in the acute course of STEMI [10].In addition, the HELP-AMI trial found immediate complete revasculari-zation a safe procedure [27], while Politi et al. found that MV-PCI wasassociated with the lowest rate of long-term cardiovascular adverseevents compared with IRA-PCI [28]. However, all randomized and pro-spective studies presented so farwere based on small study populations[10,27–30]. Kalarus et al. revealed that incomplete revascularization re-mains an independent risk factor of death and MACE in patients withSTEMI [31]. Interestingly, in the present analysis of AMIS Plus, MV-PCIwas found to be an independent negative predictor for MACCE.

Other authors suggested an approach of a staged procedure aftertreating the IRA as the most accurate choice in patients with STEMIand MVD [15,20,23,32], with the non-IRA vessels being addressed inan elective second attempt [20,23,32]. A comprehensive meta-analysisincluding 4 prospective and 14 retrospective observations found thatpatients who were staged to receive complete revascularization hadlower short- and long-term mortality when compared to those under-going immediate complete revascularization or IRA-PCI alone [20]. Incontrast, Hannan et al. supported the ACC/AHA/ESC recommendationsfor IRA-PCI in patients with STEMI andMVD but without hemodynamiccompromise [32]. However, mortality rates after risk adjustment weresimilar in both groups who underwent staged procedure for non-IRAwithin 60 days and those with a treated culprit vessel only [32]. In thepresent analysis, rates of planned revascularizations after initial PCIwere low and similar in both groups showing no relevant differencesin the interventional strategies between MV-PCI and IRA-PCI.

Table 1Baseline characteristics of STEMI patients according to vessel treatment.

Variables IRA-PCI MV-PCI p value

Number of patients 1467 442Sex, male (%) 1143/1467 (77.9) 348/442 (78.7) 0.74Age in years, mean (SD) 65.0 (11.7) 63.3 (11.6) 0.05Follow up days— median (IQR) 388 (372, 410) 387 (371, 409) 0.35Resuscitation prior to admission 51/1467 (3.5) 16/442 (3.6) 0.88Killip classes III/IV 43/1459 (2.9) 24/439 (5.5) 0.017Family history 464/1309 (35.4) 162/394 (41.1) 0.043Current smoker 542/1387 (39.1) 165/416 (39.7) 0.86Dyslipidemia 711/1273 (55.9) 214/401 (53.4) 0.39Hypertension 854/1394 (61.3) 252/430 (58.6) 0.34Obesity (BMI N 30) 273/1314 (20.8) 75/393 (19.1) 0.52Diabetes 244/1427 (17.1) 79/428 (18.5) 0.51Coronary artery disease 473/1454 (32.5) 136/440 (30.9) 0.56Heart failure 21/1448 (1.5) 5/430 (1.2) 0.82Cerebrovascular disease 70/1448 (4.8) 10/430 (2.3) 0.021Renal disease (moderate to severe) 53/1448 (3.7) 18/430 (4.2) 0.67Cancer diseases 82/1448 (5.7) 18/430 (4.2) 0.27Charlson Score ≥2 234/1448 (16.2) 64/430 (14.9) 0.55Complication during initial hospitalizationCardiogenic shock 42/1461 (2.9) 19/441 (4.3) 0.16Re-infarction 15/1464 (1.0) 3/441 (0.7) 0.78Cerebrovasular events 8/1461 (0.5) 3/441 (0.7) 0.72Bleeding 50/1461 (3.4) 16/441 (3.6) 0.88

Left main (%) 43/1467 (2.9) 55/442 (12.4) b0.001LVEF

≤35% 93/1160 (8.0) 35/370 (9.5) 0.6735–50% 443/1160 (38.2) 137/370 (37.0)≥50% 624/1160 (53.8) 198/370 (53.5)

Data are shown for single-vessel PCI versus multivessel-PCI and presented as n (%) or median with inter-quartile range (IQR);BMI = body mass index; IRA = infarct related artery, MV = multivessel, PCI = percutaneous coronary intervention;The Charlson comorbidity index gives an estimate of survival based on the following variables: cerebrovascular disease, chronic pulmonary disease, congestive heart failure, connectivetissue disease, dementia, hemiplegia, leukemia, malignant lymphoma, myocardial infarction, peripheral vascular disease, ulcer disease, diabetes mellitus, liver disease, renal disease,malignant solid tumor, and acquired immune deficiency syndrome status

79R. Jeger et al. / International Journal of Cardiology 172 (2014) 76–81

Current recommendations of ACC/AHA/ESC are based on expert con-sensus since large randomized trials are unavailable [5,33,34]. Given re-cent advancements in interventional cardiology, new stent/scaffolddesigns, and novel antiplatelet therapy, acutemultivessel revasculariza-tion could be even more beneficial for patients with STEMI, particularlyin those with a high risk of target vessel revascularization [35,36]. Thishas been corroborated in our study, since patients receiving both DESand MV-PCI had better outcomes regarding death and overall MACCEwhen compared to those receiving MV-PCI and BMS.

However, acute multivessel revascularization is nowadays stillrecommended in patients with hemodynamic compromise only, andparticularly in those with cardiogenic shock [5,37,38]. PCI for non-IRAin the acute phase of lower-risk STEMI is discouraged in current ESCguidelines and has recently been labeled as “inappropriate” by theAppropriate Use Criteria Task Force of American College of CardiologyFoundation [34,39]. MV-PCI is believed to be the potential cause of

Table 2Medication and destination at discharge of STEMI patients according to vessel treatment.

Variables IRA-PCI

Number of patients 1467Medication at dischargeASS 1447/1465 (98.8)P2Y12 blockera 1431/1466 (97.6)Beta blocker 1251/1460 (85.7)ACEI/AT 225/1448 (15.5)Statin 1415/1438 (98.4)

Destination at dischargeRehabilitation 852 (58.1)Home 391 (26.7)Transfer to other hospital/nursing home 224 (5.2)

Data are presented as n (%); ASS = acetylosalicylic acid; ACEI = angiotensin-converting-enMV = multivessel, PCI = percutaneous coronary intervention.

a Clopidogrel, prasugrel or ticagrelor.

spontaneous plaque rupture, coronary micro-embolization, iatrogenicmyocardial infarction, and coronary reserve reduction [40]. Moreover,the functional stenosis severity of non-IRA is believed to be overestimatedat the time of primary PCI [41]. Finally, the potential procedure-relatedcomplications, increased contrast use and nephropathy should not beneglected [10,27–30].

Our study has several limitations. First, as a registry, this study wasobservational in nature, and participationwas voluntary. Significant dif-ferences in baseline characteristics, i.e. age, Killip class, cardiovascularrisk factors and presence of left main stenosis could potentially influ-ence outcomes. Moreover, there is the potential for confoundingfactors due to a lack of data on relevant clinical features that may haveimpacted on both the choice to useMV-PCI aswell as outcomes. Second,although the AMIS Plus registry provides data on the number of vesselstreated with PCI, the precise anatomical distribution of the lesions andtechnical features of the procedure itself are unknown. Third, the lesions

MV-PCI p value

442

436/440 (99.1) 0.80434/441 (98.4) 0.36371/441 (84.1) 0.4456/436 (12.8) 0.19422/435 (97.0) 0.07

0.052261 (59.0)144 (32.6)37 (8.4)

zyme inhibitor; AT = angiotensin II receptor antagonists; IRA = infarct related artery,

Table 5Predictors for 1-year MACCE (composed end point of re-infarction, cerebrovascular event,interventions and/or death during follow-up period).

Variables OR 95%CI p value

Multivessel treatment 0.69 0.51–0.93 0.017Left main 1.28 0.76–2.14 0.36Female gender 1.15 0.87–1.53 0.33Age (per additional year) 0.99 0.99–1.00 0.80Charlson Index = N2 1.42 1.05–1.92 0.025Resuscitation prior admission 0.87 0.45–1.67 0.67Killip class N 2 1.76 0.99–3.12 0.052

Table 3Outcomes of STEMI patients according to vessel treatment.

Variables IRA-PCI MV-PCI p value

Number of patients 1467 442Rehospitalizationa 423/1444 (29.3) 105/432 (24.3) 0.044Re-infarction 53/1445 (3.7) 20/432 (4.6) 0.39Cerebrovascular event 8/1445 (0.6) 1/432 (0.2) 0.69Interventionsb 224/1467 (15.3) 47/442 (10.6) 0.016Pacemaker implantation 6/1160 (0.5) 3/363 (0.8) 0.45ICD 18/1160 (1.6) 6/363 (1.7) 0.81Mortality 40/1467 (2.7) 12/442 (2.7) N0.99MACCEc 294/1467 (20.0) 69/442 (15.6) 0.038

Data are presented as n (%); IRA = infarct related artery, MV = multivessel,ICD = implantable cardioverter defibrillator, MACCE = major adverse cardiovascularand cerebrovascular events, PCI = percutaneous coronary intervention.

a Due to any cardiovascular problem, diagnostic procedures, monitoring or/andinterventions.

b Any coronary intervention.c Re-infarction, stroke, intervention or death.

80 R. Jeger et al. / International Journal of Cardiology 172 (2014) 76–81

with diameter stenosis of 50–70% were not evaluated regarding ische-mia leading to a potential overtreatment in the multi-vessel PCI group.Finally, follow-up was obtained through phone calls, while eventswere not reviewed by an independent and blinded critical eventscommittee.

In conclusion, the present analysis provides insight into middle-term outcomes after multi-vessel PCI in real-world practice. It adds tothe current discussion regarding the optimal interventional treatmentstrategy in patients with STEMI and MVD. Results of the present studysupport a complete coronary revascularization attempt, particularlywhen DES are used. This suggests that PCI in the acute phase of STEMImay be expanded beyond the culprit vessel and that multi-vessel PCImight not remain restricted to high-risk groups. However, large-scaleprospective trials are needed to confirm simultaneous coronary revas-cularization as the preferred strategy during STEMI, such as the recentlystarted Complete vs Culprit-only Revascularization to TreatMulti-vesselDisease After Primary PCI for STEMI (COMPLETE Trial (ClinicalTrials.govIdentifier: NCT01740479).

Acknowledgments

AMIS Plus Hospitals participating in this studyThe authors would like to express their gratitude to the teams of the

following hospitals (listed in alphabetical order with the names of thelocal principal investigators): Aarau, Kantonsspital (P Lessing); Affolternam Albis, Bezirkspital (F Hess); Altdorf, Kantonsspital (R Simon); Baden,Kantonsspital (U Hufschmid); Basel, Universitätsspital Basel (R Jeger);Basel, St. Claraspital (C Grädel/B Hornig); Bern, Beau-Site Klinik(A Schönfelder); Bern, Tiefenauspital (P Loretan); Biel, Spitalzentrum(C Roethlisberger); Bülach, Spital (G Mang), Burgdorf; RegionalspitalEmmental (D Ryser); Davos, Spital (G Niedermaier/W Kistler); Flawil,Spital (G. Freiwald); Fribourg, Hôpital cantonal (JC Stauffer/S Cook);

Table 4Stents, treatment strategy and outcomes.

Variables DES BMS p value

Number of patients 1358 280Mortality 31/1358 (2.3) 17/280 (6.1) 0.001IRA-PCI 24/1017 (2.4) 13/226 (5.8) 0.007MVD-PCI 7/341 (2.1) 4/54 (7.4) 0.026

MACCEa 241/1358 (17.7) 76/280 (27.1) b0.001IRA-PCI 193/1017 (19.0) 62/226 (27.4) 0.006MV-PCI 48/341 (14.1) 14/54 (25.9) 0.042

Data are presented as n (%); BMS = bare-metal stent; DES = drug-eluting stent; IRA =infarct related artery, MACCE = major adverse cardiovascular and cerebrovascularevents, MV = multivessel, PCI = percutaneous coronary intervention.

a Re-infarction, stroke, intervention or death.

Frutigen, Spital (K Bietenhard); Genève, Hôpitaux universitaires(PF Keller/M Roffi); Grenchen, Spital (B Oertli/R Schönenberger);Herisau, Kantonales Spital (M Schmidli); Horgen, See Spital (BFederspiel/D Schröpfer); Interlaken, Spital (EM Weiss); Kreuzlingen,Herzzentrum Bodensee (K Weber); La Chaux-de-Fonds, Hôpital(H Zender); Langnau im Emmental, Regionalspital (A Hugi);Laufenburg, Gesundheitszentrum Fricktal (J Frei/E Koltai); Lugano,Cardiocentro Ticino (G Pedrazzini); Luzern, Kantonsspital (P Erne);Männedorf, Kreisspital (T Heimes); Mendrisio, Ospedale regionale(A Pagnamenta); Meyrin, Hôpital de la Tour (P Urban); Münsingen,Regionales Spital Zentrum (F Repond); Münsterlingen, Kantonsspital(F Widmer); Muri, Kreisspital für das Freiamt (C. Heimgartner); Nyon,Group. Hosp. Ouest lémanique (R Polikar); Olten, Kantonsspital(S Bassetti); Rheinfelden, Gesundheitszentrum Fricktal (HU Iselin);Rorschach, Kantonales Spital (MGiger); Sarnen, Kantonsspital Obwalden(T Kaeslin); Schaffhausen, Kantonsspital (R Frey/A Fischer); Schlieren,Spital Limmattal (THerren); Sion, Hôpital duValais (GGirod); Solothurn,Bürgerspital Solothurn (A Grêt/R Schönenberger/R Vogel); Stans,Kantonsspital Nidwalden (B Niggli); St. Gallen, Kantonsspital (H Rickli);Sursee, Luzerner Kantonsspital (S Yoon); Thun, Spital (U Stoller); Uster,Spital (E Bächli); Wetzikon, GZO Spital (U Eriksson); Winterthur,Kantonsspital (A Haller/T Fischer); Wolhusen, Luzerner Kantonsspital(M Peter); Zofingen, Spital (S Gasser); Zollikerberg, Spital (R Fatio);Zürich, Universitätsspital Zürich (M Maggiorini); Zürich, StadtspitalTriemli (F Eberli); and Zürich, Stadtspital Waid (M Fischler/S Christen/SBuchholz).

FundingThe AMIS Plus registry is funded by unrestricted grants from the

Swiss Heart Foundation and from Abbott AG, Switzerland; Astra-Zeneca AG, Switzerland; Bayer (Schweiz) AG, Switzerland; BiotronikAG, Switzerland; Daiichi-Sankyo/Lilly AG, Switzerland; Johnson &Johnson AG — Cordis Division, Switzerland; A Menarini AG,Switzerland; Merck Sharp & Dohme — Chibret AG, Switzerland;Medtronic AG, Switzerland; Pfizer AG, Switzerland; Servier AG,Switzerland; St. Jude Medical, Switzerland; Takeda Pharma AG,Switzerland; and Vascular Medical GmbH, Switzerland. The sponsorsdid not play any role in the design, data collection, analysis, or interpre-tation of the registry.

References

[1] Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline forpercutaneous coronary intervention: a report of the American College of CardiologyFoundation/American Heart Association Task Force on Practice Guidelines and theSociety for Cardiovascular Angiography and Interventions. Circulation 2011;124(23):e574–651.

[2] Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated percutaneouscoronary interventions for ST-elevation myocardial infarction: quantitative reviewof randomised trials. Lancet 2006;367(9510):579–88.

[3] Varani E, Balducelli M, AquilinaM, et al. Single or multivessel percutaneous coronaryintervention in ST-elevation myocardial infarction patients. Catheter CardiovascInterv 2008;72(7):927–33.

[4] Toma M, Buller CE, Westerhout CM, et al. Non-culprit coronary artery percutaneouscoronary intervention during acute ST-segment elevation myocardial infarction:insights from the APEX-AMI trial. Eur Heart J 2010;31(14):1701–7.

[5] Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization. EurHeart J 2010;31(20):2501–55.

81R. Jeger et al. / International Journal of Cardiology 172 (2014) 76–81

[6] Kushner FG, Hand M, Smith Jr SC, et al. 2009 Focused Updates: ACC/AHA guidelinesfor the management of patients with ST-elevation myocardial infarction (updatingthe 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines onpercutaneous coronary intervention (updating the 2005 guideline and 2007 focusedupdate): a report of the American College of Cardiology Foundation/American HeartAssociation Task Force on Practice Guidelines. Circulation 2009;120(22):2271–306.

[7] Jaguszewski M, Radovanovic D, Nallamothu BK, et al. for the AMIS Plus Investigators.Multivessel versus culprit vessel percutaneous coronary intervention in ST-elevationmyocardial infarction: is more worse? Eurointervention 2013;9(8):909–15.

[8] Radovanovic D, Erne P. AMIS Plus: Swiss registry of acute coronary syndrome. Heart2010;96(12):917–21.

[9] Radovanovic D, Urban P, Simon R, et al. Outcome of patients with acute coronarysyndrome in hospitals of different sizes. A report from the AMIS Plus Registry.Swiss Med Wkly 2010;140(21–22):314–22.

[10] Qarawani D, Nahir M, Abboud M, Hazanov Y, Hasin Y. Culprit only versus completecoronary revascularization during primary PCI. Int J Cardiol 2008;123(3):288–92.

[11] Erne P, Schoenenberger AW, Burckhardt D, et al. Effects of percutaneous coronaryinterventions in silent ischemia after myocardial infarction: the SWISSI II random-ized controlled trial. JAMA 2007;297(18):1985–91.

[12] Sorajja P, Gersh BJ, Cox DA, et al. Impact ofmultivessel disease on reperfusion successand clinical outcomes in patients undergoing primary percutaneous coronary inter-vention for acute myocardial infarction. Eur Heart J 2007;28(14):1709–16.

[13] Jeger RV, Pfisterer ME. Primary PCI in STEMI — dilemmas and controversies:multivessel disease in STEMI patients. Complete versus Culprit Vessel revascularizationin acute ST-elevationmyocardial infarction.Minerva Cardioangiol 2011;59(3):225–33.

[14] Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O'Neill WW. Multiplecomplex coronary plaques in patients with acute myocardial infarction. N Engl JMed 2000;343(13):915–22.

[15] Bangalore S, Kumar S, Poddar KL, Ramasamy S, Rha SW, Faxon DP. Meta-analysis ofmultivessel coronary artery revascularization versus culprit-only revascularizationin patients with ST-segment elevation myocardial infarction and multivesseldisease. Am J Cardiol 2011;107(9):1300–10.

[16] Muller DW, Topol EJ, Ellis SG, Sigmon KN, Lee K, Califf RM. Multivessel coronaryartery disease: a key predictor of short-term prognosis after reperfusion therapyfor acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarc-tion (TAMI) Study Group. Am Heart J 1991;121(4 Pt 1):1042–9.

[17] Gibson CM, Ryan KA, Murphy SA, et al. Impaired coronary blood flow in nonculpritarteries in the setting of acute myocardial infarction. The TIMI Study Group.Thrombolysis in myocardial infarction. J Am Coll Cardiol 1999;34(4):974–82.

[18] Chan MY, Andreotti F, Becker RC. Hypercoagulable states in cardiovascular disease.Circulation 2008;118(22):2286–97.

[19] Kereiakes DJ, Gurbel PA. Peri-procedural platelet function and platelet inhibition inpercutaneous coronary intervention. JACC Cardiovasc Interv 2008;1(2):111–21.

[20] Vlaar PJ, Mahmoud KD, Holmes Jr DR, et al. Culprit vessel only versus multivesseland staged percutaneous coronary intervention for multivessel disease in patientspresenting with ST-segment elevation myocardial infarction: a pairwise and net-work meta-analysis. J Am Coll Cardiol 2011;58(7):692–703.

[21] Corpus RA, House JA, Marso SP, et al. Multivessel percutaneous coronary interven-tion in patients with multivessel disease and acute myocardial infarction. AmHeart J 2004;148(3):493–500.

[22] RoeMT, Cura FA, Joski PS, et al. Initial experiencewithmultivessel percutaneous cor-onary intervention during mechanical reperfusion for acute myocardial infarction.Am J Cardiol 2001;88(2):170–3 [A176].

[23] Kornowski R, Mehran R, Dangas G, et al. Prognostic impact of staged versus “one-time” multivessel percutaneous intervention in acute myocardial infarction:analysis from the HORIZONS-AMI (harmonizing outcomes with revasculariza-tion and stents in acute myocardial infarction) trial. J Am Coll Cardiol2011;58(7):704–11.

[24] Dziewierz A, Siudak Z, Rakowski T, Zasada W, Dubiel JS, Dudek D. Impact ofmultivessel coronary artery disease and noninfarct-related artery revascularizationon outcome of patients with ST-elevation myocardial infarction transferred for

primary percutaneous coronary intervention (from the EUROTRANSFER Registry).Am J Cardiol 2010;106(3):342–7.

[25] Pedrazzini GB, Radovanovic D, Vassalli G, et al. Primary percutaneous coronary inter-vention for unprotected left main disease in patients with acute ST-segment eleva-tion myocardial infarction the AMIS (Acute Myocardial Infarction in Switzerland)plus registry experience. JACC Cardiovasc Interv 2011;4(6):627–33.

[26] Cavender MA, Milford-Beland S, Roe MT, Peterson ED, Weintraub WS, Rao SV. Prev-alence, predictors, and in-hospital outcomes of non-infarct artery intervention dur-ing primary percutaneous coronary intervention for ST-segment elevationmyocardial infarction (from the National Cardiovascular Data Registry). Am J Cardiol2009;104(4):507–13.

[27] DiMario C,Mara S, Flavio A, et al. Single vsmultivessel treatment during primary an-gioplasty: results of the multicentre randomised HEpacoat for cuLPrit or multivesselstenting for Acute Myocardial Infarction (HELP AMI) Study. Int J CardiovascIntervent 2004;6(3–4):128–33.

[28] Politi L, Sgura F, Rossi R, et al. A randomised trial of target-vessel versus multi-vesselrevascularisation in ST-elevation myocardial infarction: major adverse cardiacevents during long-term follow-up. Heart 2010;96(9):662–7.

[29] Shishehbor MH, Topol EJ, Mukherjee D, et al. Outcome of multivessel coronary inter-vention in the contemporary percutaneous revascularization era. Am J Cardiol2006;97(11):1585–90.

[30] Marenzi G, Assanelli E, Campodonico J, et al. Contrast volume during primary percu-taneous coronary intervention and subsequent contrast-induced nephropathy andmortality. Ann Intern Med 2009;150(3):170–7.

[31] Kalarus Z, Lenarczyk R, Kowalczyk J, et al. Importance of complete revascularizationin patients with acute myocardial infarction treated with percutaneous coronary in-tervention. Am Heart J 2007;153(2):304–12.

[32] Hannan EL, Samadashvili Z, Walford G, et al. Culprit vessel percutaneous coronaryintervention versus multivessel and staged percutaneous coronary intervention forST-segment elevation myocardial infarction patients with multivessel disease.JACC Cardiovasc Interv 2010;3(1):22–31.

[33] Sethi A, Bahekar A, Bhuriya R, Singh S, Ahmed A, Khosla S. Complete versus culpritonly revascularization in acute ST elevation myocardial infarction: a meta-analysis.Catheter Cardiovasc Interv 2011;77(2):163–70.

[34] Patel MR, Dehmer GJ, Hirshfeld JW, Smith PK, Spertus JA. ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT 2012 appropriate use criteria for coronary revascularization focusedupdate: a report of the American College of Cardiology Foundation Appropriate UseCriteria Task Force, Society for Cardiovascular Angiography and Interventions, Societyof Thoracic Surgeons, American Association for Thoracic Surgery, American HeartAssociation, American Society of Nuclear Cardiology, and the Society of CardiovascularComputed Tomography. J Am Coll Cardiol 2012;59(9):857–81.

[35] Varani E, Guastaroba P, Di Tanna GL, et al. Long-term clinical outcomes and cost-effectiveness analysis in multivessel percutaneous coronary interventions: compar-ison of drug-eluting stents, bare-metal stents and a mixed approach in patients athigh and low risk of repeat revascularisation. EuroIntervention 2010;5(8):953–61.

[36] Stauffer JC, Goy JJ, Duvoisin N, Radovanovic D, Rickli H, Erne P. Dramatic effect ofearly clopidogrel administration in reducing mortality and MACE rates in ACS pa-tients. Data from the Swiss registry AMIS-Plus. Swiss Med Wkly 2012;142:w13573.

[37] Thiele H, Allam B, Chatellier G, Schuler G, Lafont A. Shock in acute myocardial infarc-tion: the Cape Horn for trials? Eur Heart J 2010;31(15):1828–35.

[38] Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization and long-term sur-vival in cardiogenic shock complicating acute myocardial infarction. JAMA2006;295(21):2511–5.

[39] Steg PG, James SK, Atar D, et al. ESC Guidelines for themanagement of acutemyocar-dial infarction in patients presenting with ST-segment elevation. Eur Heart J2012;33(20):2569–619.

[40] Heusch G, Kleinbongard P, Bose D, et al. Coronary microembolization: from bedsideto bench and back to bedside. Circulation 2009;120(18):1822–36.

[41] Hanratty CG, Koyama Y, Rasmussen HH, Nelson GI, Hansen PS, Ward MR. Exaggera-tion of nonculprit stenosis severity during acute myocardial infarction: implicationsfor immediate multivessel revascularization. J Am Coll Cardiol 2002;40(5):911–6.