Yu et al.

BMC Cardiovascular Disorders (2016) 16:189

DOI 10.1186/s12872-016-0365-5

RESEARCH ARTICLE Open Access

Culprit-only versus staged complete

revascularization for patients with ST-
segment elevation myocardial infarction
and Multivessel disease: a retrospective
cohort study
Tongtong Yu, Yuanyuan Dong, Jiahe Zhu, Chunyang Tian, Zhijun Sun and Zhaoqing Sun*

Abstract
Background: Multivessel disease (MVD) is common in patients with ST-segment elevation myocardial infarction
(STEMI), but optimal treatment management remains undetermined.
Methods: In this retrospective cohort study, 602 consecutive STEMI patients with MVD were enrolled between
January 1, 2010 and October 1, 2014. Three hundred and eighty-two patients underwent culprit-only revascularization
and 220 underwent staged complete revascularization. Primary end points were a composite of cardiac mortality or
nonfatal reinfarction.
Results: The mean duration of follow-up was 35 months (12–71 months). Following multivariate analysis, staged
complete revascularization was associated with a lower rate of the composite of cardiac mortality or nonfatal
reinfarction [HR: 0.430, 95 % CI: 0.197–0.940, P = 0.034] and unplanned repeat revascularization [HR: 0.343, 95 %
CI: 0.166–0.708, P = 0.004] compared with culprit-only revascularization.
Conclusions: Compared with culprit-only revascularization, staged complete revascularization significantly
reduced the rate of the composite of cardiac mortality or nonfatal reinfarction, and the need for unplanned
repeat revascularization.
Keywords: Multivessel disease, Revascularization, ST-segment elevation myocardial infarction

Background remains undetermined [5–7]. Although a number of ran-

Primary percutaneous coronary intervention (P-PCI) of the domized controlled trials (RCTs) [8–11], including the
culprit artery is widely used in patients with ST-segment PRAMI [9], CVLPRIT [10] and DANAMI-3—PRIMULTI
elevation myocardial infarction (STEMI). Approximately [11] trials, have indicated the clear benefits of complete
50 % of STEMI patients have multivessel disease (MVD) PCI, other RCTs [12–14], including the PRAGUE-13 trial
[1, 2]. Non-culprit lesions are not just “bystanders”, as a [12], found no difference between complete and culprit-
pathophysiological inflammation process in acute myocar- only revascularization in STEMI patients with MVD. Fur-
dial infarction could cause plaque instability [3, 4]. Previous thermore, observational studies [15–21] and meta-analyses
research has also shown that STEMI patients with MVD [22–24] also demonstrated conflicting results.
have higher mortality rates and a greater incidence of non- The present study aimed to determine the benefits and
fatal reinfarction than those without MVD [1, 2]. However, safety of staged complete revascularization in STEMI
the optimal management of STEMI patients with MVD patients with MVD undergoing P-PCI.

* Correspondence: sunzhaoqing@vip.163.com
Department of Cardiology, Shengjing Hospital of China Medical University,
Shenyang, Liaoning, People’s Republic of China

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Yu et al. BMC Cardiovascular Disorders (2016) 16:189 Page 2 of 8

Methods to have MVD, which was defined as the presence of angio-

Study design and setting graphic diameter stenosis of 50 % or greater in at least one
This was a retrospective cohort study, and included con- non-culprit major epicardial coronary artery or its major
secutive STEMI patients who were hospitalized and branches (with diameter ≥2 mm). Exclusion criteria in-
underwent PCI at Shengjing Hospital of China Medical cluded (1) single vessel disease, (2) cardiogenic shock, (3)
University (Shenyang, China) between January 1, 2010 any type of stent thrombosis, (4) previous coronary artery
and October 31, 2014. Six hundred and two consecutive bypass grafting (CABG), (5) unsuitable for treatment with
cases were selected in this large-scale hospital in P-PCI, (6) chronic total occlusion as the only significant
Northeast China. Firstly, the investigators identified all non-culprit lesion, (7) non-culprit lesion in coronary ar-
consecutive PCI patients from PACS (Picture Archiving tery branches 2 mm or smaller in diameter. The study
and Communication Systems) of the interventional im- population was subdivided into (1) the culprit-only revas-
aging data and assigned each case a unique study ID. cularization group (CR group), in which only the culprit
The investigators then abstracted comprehensive clinical lesion received PCI during the index catheterization or
data and procedural data using electronic medical re- hospitalization; (2) the staged complete revascularization
cords. Abstracted elements included patient demo- group (SR group), in which, after culprit lesion PCI, a
graphic characteristics, past cardiac and noncardiac planned additional non-culprit lesion PCI was per-
history, patient clinical characteristics on hospital admis- formed during the index hospitalization, or within 1
sion, laboratory measurements, procedure-related com- month after discharge, regardless of symptoms or
plications and use of cardiac medications during the evidence of ischemia. Periprocedural and postproce-
index hospitalization and at discharge. Killip classifica- dural anti-platelet treatments and other cardiovascular
tion was introduced [5]. All venous blood samples were medications were administered in accordance with
obtained on admission and tested using autoanalyzers in current guidelines [5, 7].
the core laboratory of Shengjing Hospital and standard
techniques. Left ventricular ejection fraction (LVEF) was Clinical end points
determined by echocardiography during hospitalization. The primary end point was a composite of cardiac mor-
Procedural data from surgical records in PCI cases were tality or nonfatal reinfarction. Secondary end points
completed by operators. Angiographic variables were es- were all-cause mortality, cardiac mortality, nonfatal rein-
timated visually or by a quantitative computer analysis farction and unplanned repeat revascularization, includ-
system. Thrombolysis In Myocardial Infarction (TIMI) ing any unplanned repeat PCI or surgical bypass of
flow grade was determined as defined previously [25]. target or non-target vessels. The safety end points were
Clinical follow-up was assessed in October 2015 by hos- periprocedure-related complications, including BARC 3
pital visits or phone interviews with the patient’s general or 5 bleeding, contrast-induced nephropathy, stroke, and
practitioner/cardiologist, the patient or his/her family. acute or subacute stent thrombosis during the index
All events were obtained from the patients’ medical hospitalization. Stroke was defined as an acute event of
records. If these data were unavailable, statuses were non-hemorrhagic cerebrovascular origin causing focal or
ascertained by a telephone call to the patient’s referring global neurologic dysfunction lasting >24 h, which was
hospital physician. All events were adjudicated and clas- confirmed by both clinical and radiographic criteria.
sified by two cardiologists. Contrast-induced nephropathy was defined as an increase
in serum creatinine concentration ≥0.5 mg/dl (44.2
Participants and procedures mmol/l) or ≥25 % above baseline 72 h after exposure to
We identified 1056 STEMI patients treated with P-PCI. the contrast medium. All other end points were defined
Patients who were eligible for P-PCI met the following by standardized definitions [26, 27]. This study complies
criteria: (1) chest pain present less than 12 h from onset with the Declaration of Helsinki, and Shengjing Hospital
of pain to time of catheterization, (2) significant ST- of China Medical University Research Ethics Committee
segment elevation (at least 0.1 mV in two or more stand- approved the research protocol. Written informed consent
ard leads or at least 0.2 mV in two or more contiguous was formally obtained from all participants.
precordial leads) or a new left bundle branch block. After
confirmation of STEMI, P-PCI was immediately under- Statistical analysis
taken according to current guideline recommendations Quantitative variables with normal distribution were
and operators’ routine practice. Operators decided on the represented as mean ± standard deviation (SD) and com-
use of aspiration thrombectomy, heparin, or glycoprotein pared with the independent samples t-test. Quantitative
IIb/IIIa inhibitor. The culprit artery was determined using variables without normal distribution were represented
ECG, echocardiography and angiographic findings by each as median [interquartile range, IQR] and compared with
operator. For inclusion in the present study, patients had the Mann-Whitney U-test. Normal distribution was
Yu et al. BMC Cardiovascular Disorders (2016) 16:189 Page 3 of 8

assessed by the one-sample Kolmogorov-Smirnov Test. using a staged procedure (n = 208) and after index
Categorical variables were represented as counts and hospitalization but within 1 month (n = 12).
proportions (%) and compared using the chi-square test.
Event-free survival was estimated in the two groups Basic characteristics
from Kaplan–Meier curves and compared using the Clinical characteristics in the two groups were generally
Log-Rank Test. Cox proportional-hazards regression similar and are shown in Table 1. Periprocedural details
modeling was used to analyze the effects of variables on and discharge medication are shown in Table 2. Patients
event-free survival. Variables in Table 1 with P ≤ 0.1 at in the SR group had more stents and longer total stent
the univariate analysis were “entered” into the model length. Discharge medication was similar between the
(Table 3). These variables included age, gender, current two groups (Table 2).
smoker, and previous MI. Results were reported as haz-
ard ratios (HRs) with associated 95 % confidence inter-
vals (CIs). All tests were two-sided, and the statistical Clinical Outcome
significance was defined as P < 0.05. All statistical ana- All patients were followed for a mean duration of 35
lyses were performed using SPSS version 19 (SPSS Inc., months (12–71 months). The length of follow-up in the
Chicago, Illinois, USA). CR group was 34 months (12–69 months), and was 36
months (12–71 months) in the SR group. During the
Results follow-up period, 31 events of cardiac mortality/nonfatal
Participants myocardial reinfarction events, 17 events of cardiac mor-
Between January 1, 2010 and October 1, 2014, a total of tality, 14 events of nonfatal myocardial reinfarction, 19
1,056 patients were treated with P-PCI for STEMI in events of all-cause mortality, and 42 events of unplanned
our center. Figure 1 represents the flowchart for patient repeat revascularization were observed in the CR group;
selection. The final study cohort consisted of 602 pa- 8 events of cardiac mortality/nonfatal myocardial rein-
tients, of whom 382 (63.5 %) received culprit-only revas- farction, 4 events of cardiac mortality, 4 events of nonfa-
cularization and 220 (36.5 %) received staged complete tal myocardial reinfarction, 5 events of all-cause
revascularization. For the SR group, the timing of non- mortality, and 9 events of unplanned repeat revasculari-
culprit lesion PCI was during the index hospitalization zation were observed in the SR group. The composite of
cardiac mortality or nonfatal reinfarction was signifi-
cantly lower in the SR group compared with the CR
group [HR: 0.427, 95 % CI: 0.196–0.929, P = 0.032], and
Table 1 Demographics and baseline clinical characteristics, unplanned repeat revascularization showed a similar
means ± SD, or N (%) trend [HR: 0.349, 95 % CI: 0.170–0.717, P = 0.004] (Fig. 2;
CR, n = 382 SR, n = 220 P Table 3). After adjusting for covariates (Model 1), the SR
Age, yrs 64.6 ± 12.0 62.7 ± 11.5 0.052 group was still associated with a lower rate of the com-
Male 257 (67.3) 164(74.5) 0.061 posite of cardiac mortality or nonfatal reinfarction [HR:
Medical history 0.430, 95 % CI: 0.197–0.940, P = 0.034] and unplanned
Diabetes 101 (26.4) 70 (31.8) 0.159 repeat revascularization [HR: 0.343, 95 % CI: 0.166–
0.708, P = 0.004] compared with the CR group (Table 3).
Hypertension 194 (50.8) 120 (54.5) 0.374
There were no statistically significant differences in the
Hypercholesterolemia 100 (26.2) 56 (25.5) 0.845
other endpoints between the two groups (Table 3).
Current smoker 194 (50.8) 128 (58.2) 0.080 Periprocedure-related complications were not signifi-
Previous PCI 14 (3.7) 10 (4.5) 0.595 cantly different (Table 4).
Previous MI 13 (3.4) 14 (6.4) 0.091
Killip class II/III on admission 27 (7.1) 13 (5.9) 0.582 Discussion
Systolic blood pressure on 128.2 ± 22.0 129.9 ± 24.0 0.392 The present study determined the effects of different
admission, mmHg treatment strategies on STEMI patients with MVD
Heart rate on admission, bpm 77.3 ± 16.8 77.8 ± 14.5 0.703 in a real-world clinical setting. The main findings
LVEF, % 54.0 ± 9.1 53.6 ± 9.1 0.662 were as follows: (1) staged complete revasculariza-
Symptom to balloon time, h 6 (4,9) 6 (3,9) 0.851
tion significantly reduced not only the rate of the
composite of cardiac mortality or nonfatal reinfarc-
Anterior MI 165 (43.2) 103 (46.8) 0.389
tion, but also the need for unplanned repeat revascu-
Three-vessel disease 160 (41.9) 106 (48.2) 0.134 larization; (2) no significant differences in all-cause
Intra-aortic Balloon Pump 31 (8.1) 17 (7.7) 0.866 mortality, cardiac mortality or nonfatal reinfarction
MI myocardial infarction, bpm beats per minute, h hour were observed between the treatment strategies; (3)
Yu et al. BMC Cardiovascular Disorders (2016) 16:189 Page 4 of 8

Fig. 1 Flow diagram of participant selection. 330 with single vessel disease, 70 with other exclusion criteria, and 44 without follow-up were excluded.
The final study cohort consisted of 602 patients, of whom 382 received culprit-only revascularization and 220 received staged complete
revascularization. STEMI, ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass
grafting; N-IRA, non-Infarct-Related Artery

staged complete revascularization did not significantly mortality and nonfatal reinfarction between the two
increase periprocedure-related complications. groups. It was demonstrated that staged complete revas-
Toyota et al. analyzed 1311 STEMI patients with cularization significantly reduced the need for unplanned
MVD undergoing P-PCI from the CREDO-Kyoto AMI repeat revascularization; however, the Japanese study [19]
Registry in Japan (681 in the staged PCI group versus and CvLPRIT trial [10] found no significant differ-
630 in the culprit-only PCI group), and reported that ences, and the proportion of patients with three-vessel
staged PCI was associated with a lower 5-year composite disease may have played an important role. There was
of cardiac mortality and myocardial infarction compared a higher proportion of three-vessel disease in the CR
with culprit-only PCI [HR: 0.67, 95 % CI: 0.44–0.99, P = group in our study than in the other two previous
0.045] [19]. Our findings also showed a lower composite studies. In other words, the higher the proportion of
of cardiac mortality and nonfatal reinfarction in the SR three-vessel disease, the higher the proportion of
group. A similar conclusion was found in the CvLPRIT ischemia-driven unplanned repeat revascularizations.
and DANAMI-3—PRIMULTI trials [10, 11]. However, Meta-analyses have also confirmed that multivessel
no studies have found significant differences in cardiac PCI will reduce the need for repeat revascularization
mortality [8–12, 19] between the treatment groups. Fur- [22–24]. Different to other studies [17–19], our study
thermore, most studies [8–12, 17, 19, 20] found no signifi- found no significant differences in all-cause mortality.
cant differences in nonfatal reinfarction, except for the It is possible that the follow-up duration in our study
PRAMI trial [9] and a recent meta-analysis [23]. Our was too short to detect significant differences in all-
study also failed to find significant differences in cardiac cause mortality: 3-year follow-up in our study,
Yu et al. BMC Cardiovascular Disorders (2016) 16:189 Page 5 of 8

Table 2 Periprocedural details and discharge medication, There are still several problems related to the treat-
median (IQR), or N (%) ment of STEMI. First, is staged complete revasculari-
CR, n = 382 SR, n = 220 P zation better than "one-time" complete revascularization?
Percutaneous coronary intervention While analysis from the HORIZONS-AMI trial preferred
TIMI flow grade 0/1 on arrival 288 (75.4) 165 (75.0) 0.914 staged complete revascularization [15], other studies
found "one-time" complete revascularization safe and
TIMI flow grade 3 post-PCI 375 (98.2) 218 (99.1) 0.369
effective [20, 21]. Second, what is the appropriate
Number of stents 1 (1,2) 3 (2,4) <0.001
timing of staged revascularization? Different studies
Stent type 0.211 had different time cut-off points; however, no study
No stenting 9 (2.4) 1 (0.5) could confirm a favored time cut-off point. Third,
Bare metal 2 (0.5) 1 (0.5) should fractional flow reserve (FFR) or a non-invasive
Drug-eluting 371 (97.1) 218 (99.1) physiological stress test be used to determine indica-
tions for staged revascularization in addition to angi-
Total stent length for all lesions 36 (24,57) 79 (54,109) <0.001
treated, mm ography? FFR measurements of non-culprit lesions
Lesion site in culprit vessel 0.700
could be performed immediately [28] or several days
or weeks [7] after treatment of the culprit vessel. To
Left anterior descending artery 169 (44.2) 95 (43.2)
date, studies with FFR as the reference [11, 13, 14] did
Left circumflex artery 48 (12.6) 33 (15.0) not have clearer conclusions than those without FFR as the
Right coronary artery 165 (43.2) 92 (41.8) reference [8–10]. The COMPARE ACUTE trial (Clinical-
Thrombus aspiration catheter used 55 (14.4) 27 (12.3) 0.464 Trials.gov NCT01399736), an ongoing prospective ran-
Use of glycoprotein IIb/IIIa inhibitor 142 (37.2) 127 (42.3) 0.217 domized study comparing a FFR-guided multivessel PCI
Medical treatment at discharge
undertaken during primary PCI of the culprit vessel only,
may help us to define the role of FFR in STEMI patients
Aspirin 376 (98.4) 217 (98.6) 0.840
with MVD. Fourth, do the benefits extend to non-
Clopidogrel 373 (97.6) 213 (96.8) 0.544 culprit stenoses of less than 70 % or 50 %? The level of
Ticagrelor 5 (1.3) 5 (2.3) 0.373 non-culprit stenosis at which the risks of PCI surpass
Statin 358 (93.7) 203 (92.3) 0.498 the benefits is still uncertain. In addition to FFR, intra-
Beta-blockers 224 (58.6) 115 (52.1) 0.121 coronary imaging such as an intravascular ultrasound
Angiotensin-converting enzyme 224 (58.6) 133 (60.5) 0.662
study (IVUS) and optical coherence tomography (OCT)
inhibitors/Angiotensin receptor could be useful tools for non-culprit lesion revasculari-
blockers zation. IVUS and OCT could help us describe in vivo
Calcium-channel blocker 24 (6.3) 9 (4.1) 0.255 the pathological morphology of plaque associated with
Nitrate 39 (10.2) 16 (7.3) 0.228 an impaired myocardial blush and slow flow leading to
Nicorandil 20 (5.2) 6 (2.7) 0.145
a worse prognosis [29]. As for the use of IVUS and
OCT, a per-patient tailored therapy may be achieved.

Limitations
compared with 5-year and 7-year follow-up in the This study had several limitations. First, the study was
other two studies [18, 19]. In addition, the sample size retrospective and observational, thus potential confounders
in our study was relatively small, 602 individuals com- and selection bias could not be completely adjusted. Sec-
pared with 8822 and 1311 in the other two studies [18, ond, this was a single center study. Third, the significance
19]. Accordingly, adequately powered randomized of non-culprit lesions was assessed only on angiography,
studies should be performed to obtain meaningful con- and ischemia tests such as FFR were absent. Fourth, the
clusions, such as in the COMPLETE trial (Clinical- long symptom to balloon time in this study may have had
Trials.gov NCT01740479). an impact on the study results, as analysis of the
The safety concerns regarding complete revasculariza- HORIZONS-AMI trial results suggested that a delay in
tion include the risk of procedural complications, longer mechanical reperfusion therapy during STEMI is associ-
procedural time, contrast nephropathy, and stent throm- ated with greater injury to the microcirculation [30], and
bosis which may increase in a prothrombotic and pro- another study showed that a symptom-onset-to-balloon
inflammatory state in the presence of STEMI. Despite time >4 h was an independent predictor of one-year mor-
this, our study showed no increase in major bleeding, tality [31]. Finally, the incidence of the primary composite
contrast-induced nephropathy, stroke, acute or sub- end-point was quite low during the follow-up period. The
acute stent thrombosis. This was consistent with previous low number of events may be a limitation in the overall
studies [8, 10–12, 19]. interpretation of the study results.
Yu et al. BMC Cardiovascular Disorders (2016) 16:189 Page 6 of 8

Fig. 2 Kaplan-Meier survival curves free from (a) cardiac mortality/nonfatal reinfarction, (b) cardiac mortality, (c) nonfatal reinfarction, (d) all-cause
mortality, (e) unplanned repeat revascularization according to the different groups. SR, staged complete revascularization group; CR, culprit-only
revascularization group

Table 3 Univariate and multivariate analysis of the effects of different treatment strategies at follow-Up, N (%)
No. patients with event Univariate analysis Multivariate analysis*
CR SR HR (95 % CI) P HR (95 % CI) P
Primary end points
Cardiac mortality/Nonfatal reinfarction 31 (8.1) 8 (3.6) 0.427 (0.196–0.929) 0.032 0.430 (0.197–0.940) 0.034
Secondary end points
Cardiac mortality 17 (4.5) 4 (1.8) 0.400 (0.135–1.190) 0.100 0.440 (0.147–1.319) 0.143
Nonfatal reinfarction 14 (3.7) 4 (1.8) 0.467 (0.153–1.418) 0.179 0.442 (0.143–1.365) 0.156
All-cause mortality 19 (5.0) 5 (2.3) 0.442 (0.165–1.185) 0.105 0.489 (0.181–1.321) 0.158
Unplanned repeat revascularization 42 (11.0) 9 (4.1) 0.349 (0.170–0.717) 0.004 0.343 (0.166–0.708) 0.004
*Adjusted for age, diabetes, hypertension, Killip class II/III on admission, systolic blood pressure on admission, heart rate on admission, symptom to balloon time,
and anterior MI
Yu et al. BMC Cardiovascular Disorders (2016) 16:189 Page 7 of 8

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Funding
versus treatment of the culprit lesion only in patients with ST-segment
This research project was supported by grants from the Social Development
elevation myocardial infarction and multivessel disease (DANAMI-
Research Program of Liaoning Province (2011225020).
3—PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015;
386(9994):665-671
Availability of data and materials 12. Hlinomaz O. Multivessel coronary disease diagnosed at the time of primary
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