Culprit Vessel-Only vs. Staged Multivessel Percutaneous Coronary Intervention Strategies in Patients With Multivessel Coronary Artery Disease Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction

Abstract

Background: We assessed the current status of treatment strategy in ST-segment elevation myocardial infarction (STEMI) with multivessel disease (MVD) in real world practice, focusing on the benefit of staged percutaneous coronary intervention (PCI).

Methods and Results: From the CREDO-Kyoto AMI Registry, 2,010 STEMI patients with MVD undergoing primary PCI were analyzed. Only 96 patients (4.8%) received acute multivessel PCI, and the majority of patients (n=1,914, 95.2%) had culprit-only PCI acutely. After excluding 699 patients (acute multivessel PCI, Killip class ≥3, age ≥90 years, coronary artery bypass grafting within 90 days, or clinical events within 90 days), 681 MVD patients underwent staged PCI for angiographically significant non-culprit lesions within 90 days (staged PCI group), while 630 MVD patients received primary PCI only (culprit-only PCI group). The cumulative 5-year incidence of and adjusted risk for all-cause death were significantly lower in the staged PCI group compared with the culprit-only PCI group (9.5% vs. 16.0%, P<0.001; HR, 0.69; 95% CI: 0.50–0.96, P=0.03). The risks for MI and any coronary revascularization favored the staged PCI strategy.

Conclusions: The staged PCI strategy for angiographically significant non-culprit lesions was associated with lower 5-year mortality compared with the culprit-only PCI strategy in STEMI patients with MVD who underwent primary PCI. (Circ J 2016; 80: 371–378)

Appropriate management strategy for significant non-culprit lesion in ST-segment elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease (MVD) undergoing primary percutaneous coronary intervention (PCI) has not been adequately established as yet. Current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines and European Society of Cardiology (ESC) guidelines for the management of STEMI recommend that PCI should not be performed in a non-infarct artery at the time of primary PCI in hemodynamically stable STEMI patients.^1,2 Recently, the Preventive Angioplasty in Acute Myocardial Infarction (PRAMI) trial reported long-term clinical benefit of non-culprit lesion PCI in the acute myocardial infarction (AMI) setting: the patients who received non-culprit lesion PCI had significantly lower cumulative 3-year incidence of the primary endpoint (composite of cardiac death, non-fatal MI, and refractory angina) as compared with the patients treated with the culprit-vessel-only PCI strategy.³ The trial protocol strongly discouraged the scheduled staged PCI procedure, but treatment of the non-culprit lesion in a staged manner is considered the standard strategy in current clinical practice. Nevertheless, it is not known whether the staged PCI strategy could improve clinical outcome as compared with the culprit-only PCI strategy in a manner similar to acute multivessel PCI, as evaluated in the PRAMI trial.⁴ Therefore, we evaluated the clinical outcomes of staged multivessel PCI strategy as compared with the culprit vessel-only PCI strategy in STEMI patients with MVD in a large observational database of patients with AMI in Japan.

Editorial p 318

Methods

The Coronary REvascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction (CREDO-Kyoto AMI) registry is a physician-initiated non-company sponsored multicenter registry that enrolled consecutive AMI patients who underwent coronary revascularization between January 2005 and December 2007 at 26 tertiary hospitals in Japan (Appendix S1). The study design and patient enrollment of the registry have previously been described in detail.^5–7 Among 5,429 patients enrolled in the registry, the study population for the current analysis consisted of 2,010 STEMI patients who underwent primary PCI within 24 h of symptom onset, excluding patients who refused study participation, patients with prior coronary artery bypass grafting (CABG) or treated with CABG in the acute setting, non-STEMI patients, and patients who underwent PCI beyond 24 h after symptom onset or whose symptom onset was unknown, and patients with single-vessel disease (Figure 1).

Figure 1.

Study flow chart. AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; CREDO-Kyoto AMI Registry, Coronary REvascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction registry; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Due to retrospective enrollment, written informed consent was waived, but we excluded those patients who refused to participate in the study when contacted for follow-up. Patient records were anonymized and de-identified before analysis. The research protocol including waiver of informed consent was approved by the local ethics committees in all of 26 participating medical centers (Kyoto University Hospital, Kishiwada City Hospital, Tenri Hospital, Hyogo Prefectural Amagasaki Hospital, Kitano Hospital, Koto Memorial Hospital, Kokura Memorial Hospital, Maizuru Kyosai Hospital, Nara Hospital Kinki University Faculty of Medicine, Kobe City Medical Center General Hospital, Nishi-Kobe Medical Center, Kansai Denryoku Hospital, Osaka Red Cross Hospital, University of Fukui Hospital, Shizuoka City Shizuoka Hospital, Hamamatsu Rosai Hospital, Shiga University of Medical Science Hospital, Japanese Red Cross Wakayama Medical Center, Shimabara Hospital, Kagoshima University Medical and Dental Hospital, Shizuoka General Hospital, Kurashiki Central Hospital, Mitsubishi Kyoto Hospital, Kumamoto University Hospital, Shimada Municipal Hospital, and Juntendo University Shizuoka Hospital).

Staged PCI was pre-specified as PCI for the non-culprit lesion scheduled during the index hospitalization and performed within 90 days of the index PCI. The primary outcome measure in the current analysis was all-cause death. The secondary outcome measures included cardiac death, non-cardiac death, MI, stroke, any coronary revascularization, and a composite of cardiac death or MI. Death was regarded as cardiac in origin unless obvious non-cardiac causes could be identified. Any death during hospitalization for the index AMI was regarded as cardiac death. MI was defined according to the definition in the Arterial Revascularization Therapy Study.⁸ Stroke was defined as ischemic or hemorrhagic stroke either occurring during the index hospitalization or requiring hospitalization with symptoms lasting >24 h. Any coronary revascularization was defined as either PCI or CABG for any reason.

Experienced clinical research coordinators from the independent clinical research organization (Appendix S2) collected baseline clinical, angiographic and procedural characteristics from hospital charts or hospital databases according to the pre-specified definitions. Collection of follow-up information was mainly conducted through review of hospital charts by the clinical research coordinators, and additional follow-up information was collected through contact with patients, relatives and/or referring physicians by mail. Death, MI, and stroke were adjudicated by the clinical event committee (Appendix S3). Median follow-up duration for the surviving patients was 1,956 days (IQR, 1,668–2,221 days).

Continuous variables are expressed as mean±SD, or median (IQR). Categorical variables are expressed as numbers and percentages. We compared continuous variables using Student’s t-test or Wilcoxon rank-sum test on the basis of the distributions. We compared categorical variables using chi-squared test when appropriate; otherwise, Fisher’s exact test was used.

We conducted a landmark analysis at 90 days after the index primary PCI to compare clinical outcome between the culprit-only PCI and the staged multivessel PCI strategy in STEMI patients with MVD. Cumulative incidence of clinical events was estimated using the Kaplan-Meier method, and differences were assessed with log-rank test. Multivariate Cox proportional hazards models were used to estimate hazards ratio of the staged multivessel PCI strategy relative to the culprit-only PCI strategy for the primary and secondary outcome measures, and we calculated the adjusted event curves of the 2 groups using the methods described by Ghali et al.⁹ Because of the small number of events for the outcome measures except for any coronary revascularization, we selected 15 clinically relevant risk-adjusting variables (Tables 1,2) for these multivariate Cox proportional hazard models. For any coronary revascularization, we used 37 clinically relevant risk-adjusting variables (Tables 1,2) consistent with our previous reports. Furthermore, we performed propensity score matching analysis as a sensitivity analysis (Supplementary Methods).

Table 1. Baseline Characteristics vs. PCI Strategy

	Culprit-only PCI	Staged PCI	P-value
No. patients	630	681
Patient characteristics
Age (years)	68.1±11.6	66.2±10.5	0.001
Age ≥75 years†,‡	211 (33)	153 (22)	<0.001
Male†	459 (73)	537 (79)	0.01
Body mass index (kg/m2)	23.8±3.5	23.8±3.3	0.33
Body mass index <25 kg/m2 †,‡	444 (70)	478 (70)	0.91
Hypertension†	512 (81)	543 (80)	0.48
Diabetes	225 (36)	235 (35)	0.65
Insulin use†,‡	27 (4.3)	35 (5.1)	0.47
Current smoking†	225 (36)	309 (45)	<0.001
LVEF (%)	54.1±12.7	54.9±11.5	0.35
LVEF ≤40%	71/511 (14)	61/539 (11)	0.21
Prior stroke†,‡	59 (9.4)	51 (7.5)	0.22
Heart failure†,‡	106 (17)	95 (14)	0.15
Mitral regurgitation ≥3†	11 (1.8)	23 (3.4)	0.06
Prior MI†,‡	65 (10)	50 (7.3)	0.06
Atrial fibrillation†	49 (7.8)	43 (6.3)	0.30
Dialysis†,‡	12 (1.9)	8 (1.2)	0.28
eGFR <30 ml/min/1.73 m2, not on dialysis†,‡	21 (3.3)	7 (1.0)	0.004
Anemia (hemoglobin <11 g/dl)†,‡	47 (7.5)	40 (5.9)	0.25
Platelet <100×109/L†	7 (1.1)	6 (0.9)	0.67
Chronic obstructive pulmonary disease†	24 (3.8)	10 (1.5)	0.008
Liver cirrhosis†	8 (1.3)	14 (2.1)	0.27
Peripheral arterial disease†,‡	20 (3.2)	13 (1.9)	0.14
Malignancy†,‡	54 (8.6)	47 (6.9)	0.26
Characteristics of STEMI
Time from symptom onset to admission (h)	2.6 (1.2–5.6)	2.8 (1.3–6.0)	0.34
Onset-to-balloon time (h)	4.6 (3.1–7.9)	4.3 (2.9–7.7)	0.21
Onset-to-balloon time >180 min†,‡	424/565 (75)	424/594 (71)	0.16
Door-to-balloon time (h)	1.7 (1.2–2.4)	1.4 (0.9–2.1)	<0.001
Door-to-balloon time >90 min	328/555 (59)	244/581 (42)	<0.001
Location of STEMI			0.17
Anterior	265 (42)	261 (38)
Non-anterior	365 (58)	420 (62)
Peak creatinine phosphokinase (IU/L)	2,059 (1,029–3,794)	2,159 (1,073–3,898)	0.62
Medications at discharge
Aspirin	626 (99)	681 (100)	0.053
Thienopyridine	607 (96)	680 (100)	<0.001
Cilostazole†	238 (38)	236 (35)	0.24
Statins†,‡	355 (56)	427 (63)	0.02
ACEI/ARB†,‡	497 (79)	545 (80)	0.61
β-Adrenergic blockers†	263 (42)	306 (45)	0.24
Calcium channel blockers†	154 (24)	136 (20)	0.051
Nitrates†	193 (31)	239 (35)	0.09
Nicorandil†	209 (33)	195 (29)	0.08
Warfarin†	65 (10)	50 (7.3)	0.06
Proton pump inhibitors†	204 (32)	234 (34)	0.45
H2 blockers†	234 (37)	239 (35)	0.44

Data were given as mean±SD, median (IQR) or n (%). ^†Potential independent variables selected for multivariate analysis for any coronary revascularization. ^‡Potential independent variables selected for multivariate analysis for all-cause death, cardiac death, non-cardiac death, MI, stroke and a composite of cardiac death or MI. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate; H2 blocker, histamine type 2 receptor blocker; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation MI.

Table 2. Angiographic and Procedural Characteristics vs. PCI Strategy

	Culprit-only PCI	Staged PCI	P-value
Primary PCI procedures
No. diseased vessels			<0.001
Double-vessel disease	432 (69)	401 (59)
Triple-vessel disease	168 (27)	254 (37)
Left main coronary artery disease	30 (4.8)	26 (3.8)
Lesion location
Left anterior descending coronary artery	527 (84)	611 (90)	0.001
Right coronary artery	469 (74)	571 (84)	<0.001
Left circumflex coronary artery	422 (67)	442 (65)	0.43
Left main coronary artery	30 (4.8)	26 (3.8)	0.40
Target proximal left anterior descending coronary artery‡	252 (40)	251 (37)	0.24
Target unprotected left main coronary artery	14 (2.2)	7 (1.0)	0.09
No. implanted stents	1.28±0.60	1.33±0.63	0.19
Total stent length (mm)	26.5±13.1	28.4±14.4	0.006
Total stent length >28 mm	169/582 (29)	220/657 (33)	0.09
Minimum stent diameter (mm)	3.1±0.5	3.1±0.4	0.45
Minimum stent diameter <3.0 mm	155/582 (27)	166/657 (25)	0.58
Staged PCI procedures
Target proximal left anterior descending coronary artery	–	319 (47)
Target unprotected left main coronary artery	–	18 (2.6)
No. implanted stents	–	1.6±1.0
Total stent length (mm)	–	35.4±21.9
Total stent length >28 mm	–	307/653 (47)
Minimum stent diameter (mm)	–	2.8±0.4
Minimum stent diameter <3.0 mm	–	339/653 (52)
Overall revascularization procedures
Target proximal left anterior descending coronary artery†	253 (40)	556 (82)	<0.001
Target unprotected left main coronary artery†	14 (2.2)	25 (3.7)	0.12
Target bifurcation†	111 (18)	300 (44)	<0.001
Drug-eluting stent use†	151/582 (26)	479/681 (70)	<0.001
Side-branch stenting†	5 (0.8)	50 (7.3)	<0.001
No. implanted stents	1.31±0.57	2.89±1.23	<0.001
Total stent length (mm)	26.5±13.1	61.4±28.9	<0.001
Total stent length >28 mm†	170/582 (29)	637/681 (94)	<0.001
Minimum stent diameter (mm)	3.1±0.5	2.8±0.4	<0.001
Minimum stent diameter <3.0 mm†	155/582 (27)	389/681 (57)	<0.001

Data were given as mean±SD or n (%). ^†Potential independent variables selected for multivariate analysis for any coronary revascularization. ^‡Potential independent variables selected for multivariate analysis for all-cause death, cardiac death, non-cardiac death, MI, stroke and composite of cardiac death and MI. Abbreviations as in Table 1.

Statistical Analysis

All statistical analysis was conducted using JMP 10.0 (SAS Institute, Cary, NC, USA) and adjusted event curves for the 2 groups were calculated using SAS 9.4 (SAS Institute). All statistical analysis was 2-tailed and P<0.05 was considered statistically significant.

Results

Among 2,010 patients with MVD, the majority of patients (n=1,914, 95.2%) received culprit vessel-only PCI in the acute setting and 96 patients received acute PCI for non-culprit lesion in addition to culprit vessel PCI (multivessel PCI strategy). Patients who underwent acute multivessel PCI more often had compromised hemodynamic status than those who underwent culprit vessel-only PCI in the acute setting (Table S1). Among 1,914 patients receiving culprit-only PCI at the time of primary PCI, we excluded 366 patients with Killip class 3/4, 35 patients ≥90 years of age, and 47 patients who underwent CABG within 90 days, because these patients were unlikely to undergo scheduled staged PCI. In the remaining 1,466 patients with MVD, 733 patients were treated with scheduled staged PCI within 90 days of the index primary PCI procedure, while 733 patients were treated with culprit-only PCI. After excluding 155 patients with clinical events such as death, MI, stroke, and unplanned coronary revascularization within 90 days of the index primary PCI procedure (Table S2), long-term clinical outcome in the staged PCI group (n=681) was compared with that in the culprit-only PCI group (n=630) on 90-day landmark analysis (Figure 1).

In the staged PCI group, the majority of the staged PCI procedures were performed early after primary PCI (median interval from index PCI to the first staged PCI procedure, 13 days; IQR, 8–18 days; Figure S1).

Regarding baseline characteristics, the culprit-only PCI group had higher prevalence of advanced age, renal dysfunction, chronic obstructive pulmonary disease, and longer door-to-balloon time, whereas the staged PCI group more often were male and current smokers. Compared with patients in the culprit-only PCI group, patients in the staged PCI group were more frequently prescribed thienopyridine, and statins (Table 1). Procedural characteristics of the primary PCI procedure was generally similar between the staged PCI and culprit-only PCI groups except for the total stent length in the staged PCI group (Table 2).

The cumulative 5-year incidence of all-cause death in the staged PCI group was significantly lower than that in the culprit-only PCI group on 90-day landmark analysis (Figure 2; Table 3). After adjusting for confounders, the risk of all-cause death remained significantly lower in the staged PCI group than in the culprit-only PCI group (Figure 2; Table 3). The risk for a composite of cardiac death or MI was also significantly lower in the staged PCI group than in the culprit-only PCI group (Figure 2; Table 3). The risk for cardiac death in the staged PCI group tended to be lower than that in the culprit-only PCI group (Table 3). The risks for the other clinical outcomes including non-cardiac death, MI, stroke, and any coronary revascularization were not significantly different between the staged PCI group and the culprit-only PCI group (Table 3).

Figure 2.

Crude and adjusted clinical outcome: staged percutaneous coronary intervention (PCI) group vs. culprit-only PCI group. (A) All-cause death, and (B) composite of cardiac death or myocardial infarction (MI). The crude cumulative incidences of and adjusted risks for all-cause death and composite of cardiac death or MI were significantly higher in the culprit-only PCI group (red lines) than in the staged PCI group (blue lines).

Table 3. Crude and Adjusted 5-Year Outcomes

	No. patients with event (cumulative incidence)		Crude HR (95% CI)	P-value	Adjusted HR (95% CI)	P-value
	Culprit-only PCI	Staged PCI
All-cause death	95 (16.0)	59 (9.5)	0.58 (0.43–0.78)	<0.001	0.69 (0.50–0.96)	0.03
Cardiac death	36 (6.3)	23 (3.7)	0.56 (0.34–0.90)	0.02	0.60 (0.35–1.01)	0.06
Non-cardiac death	59 (10.4)	36 (6.0)	0.59 (0.40–0.86)	0.006	0.77 (0.50–1.17)	0.22
MI	30 (5.4)	24 (4.0)	0.62 (0.37–1.02)	0.06	0.74 (0.42–1.28)	0.28
Stroke	33 (5.7)	21 (3.4)	0.58 (0.34–0.95)	0.03	0.79 (0.45–1.38)	0.41
Any coronary revascularization	227 (38.6)	289 (43.7)	1.12 (0.95–1.33)	0.19	0.86 (0.65–1.13)	0.27
Cardiac death or MI	60 (10.6)	42 (6.8)	0.57 (0.39–0.82)	0.003	0.67 (0.44–0.99)	0.045

CI, confidence interval; HR, hazard ratio. Other abbreviations as in Table 1.

Results of propensity score matching analysis were concordant with the main analysis, and the trends of lower risk for all-cause death and cardiovascular outcomes in the staged PCI group compared with the culprit-only PCI group were also consistent with the main analysis (Tables S3,S4; Figure S2).

Discussion

The main findings of the present study were as follows: (1) multivessel PCI for angiographically significant non-culprit lesions in the acute STEMI setting is rarely performed in real world practice; (2) nearly half of STEMI patients with MVD receive staged PCI for angiographically significant non-culprit lesion within 90 days after primary PCI; and (3) the staged PCI strategy is associated with significantly lower 5-year mortality compared with the culprit-only PCI strategy.

The optimal treatment strategy for STEMI patients with MVD has not been established as yet. In STEMI patients with MVD undergoing primary PCI, there are 3 possible strategies for the management of significant non-culprit lesions: (1) acute multivessel PCI strategy: treating both culprit lesion and significant non-culprit lesions at the time of primary PCI; (2) culprit-only PCI strategy: treating only the culprit lesion in primary PCI and subsequent medical therapy without coronary revascularization unless refractory ischemia occurs; and (3) staged PCI strategy: treating only the culprit lesion at the time of primary PCI and performing planned additional coronary revascularization for significant non-culprit lesions as a staged PCI procedure.¹⁰ Current ACCF/AHA guidelines and ESC guidelines for the management of STEMI state that PCI should not be performed in a non-infarct artery at the time of primary PCI in hemodynamically stable STEMI patients.^1,2 Contrary to the clinical guidelines and previous reports, the PRAMI randomized trial, in which 465 STEMI patients with MVD were randomly assigned to multivessel PCI at the time of primary PCI (“preventive PCI”) or PCI limited to the infarct artery (non-preventive PCI), recently reported that “preventive PCI” significantly reduced the risk of adverse cardiovascular events as compared with “non-preventive PCI”. In the PRAMI trial, however, the staged PCI in patients without angina was strongly discouraged after assignment.³ Therefore, this study did not indicate the superiority of multivessel “preventive PCI” strategy over staged PCI strategy. In the present study, the prevalence of multivessel PCI at the time of primary PCI was limited in real world practice, in keeping with the recommendation of clinical guidelines. Even if contemporary PCI has become a safer procedure, there remain concerns regarding the safety of multivessel PCI at the time of primary PCI. Furthermore, it is difficult to evaluate the physiologic significance of non-culprit lesions in the setting of AMI. In the PRAMI trial, enrollment in the trial was based on visual estimation of angiographic stenosis. The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) trial showed improvement of clinical outcome after fractional flow reserve-guided PCI as compared with angiography-guided PCI in MVD patients.¹¹ In the current observational study, most of the staged PCI procedures were performed early after primary PCI to minimize the potential high-risk period related to the presence of significant non-culprit lesions. The staged PCI strategy could allow us to evaluate the physiological significance of the non-culprit lesion either via non-invasive functional assessment or via fractional flow reserve measurement, and, therefore, seems to be a more attractive alternative to preventive PCI.

It remains unclear, however, whether the appropriate management for STEMI patients with MVD is culprit-only PCI or staged PCI strategy. Hannan et al reported that mortality in the staged PCI group (n=538) tended to be lower compared with the culprit-only PCI group (n=538) in their propensity-matched cohort.¹² Bainey et al reported improved long-term survival with the staged multivessel PCI strategy in a meta-analysis of 26 studies (3 randomized, 23 non-randomized; 7,886 multivessel PCI and 38,438 culprit-only PCI). The meta-analysis, however, contained large heterogeneity due to variations in results and the timing of non-culprit lesion PCI procedures across included studies.¹³ In the majority of the previous observational studies evaluating the impact of multivessel PCI for non-culprit lesions, including the Hannan et al study, the proportion of patients receiving multivessel PCI was much lower than in the current study (Hannan et al, 13.4%; present study, 51.9%). Consistent with the previous studies, the current observational study showed the benefit of staged PCI for non-culprit lesions compared with culprit-only PCI for long-term mortality. Multivessel PCI for non-culprit lesions might have the potential to stabilize both electrophysiological and hemodynamic conditions in the acute infarct phase and to prevent future ischemic events on non-culprit but unstable lesions, thereby providing mortality benefit over culprit-only PCI. Currently ongoing, the Complete versus Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI (COMPLETE) trial (ClinicalTrials.gov Identifier NCT01740479), which is an international randomized clinical trial comparing staged PCI strategy with culprit-only PCI strategy in 3,900 STEMI patients with MVD, would provide further guidance for the appropriate management of STEMI patients with MVD. Although the benefit of staged PCI for angiographically significant non-culprit lesions after primary PCI was suggested in the current study, there remain issues to be solved such as the appropriate timing of staged PCI, as well as the method of determining indications for staged PCI (angiography only, non-invasive physiological stress test or fractional flow reserve during invasive coronary angiography). Adequately designed prospective randomized trials are clearly needed to define the role of staged PCI in STEMI patients with MVD.

This study had several limitations. First, despite the appropriate statistical adjustment for potential confounders, the observational study design precluded definitive conclusions because of selection bias regarding the decision making for staged PCI, and unmeasured confounders. Sicker patients, particularly those with medical comorbidities, are less likely to undergo staged PCI unless they have refractory symptoms due to non-culprit lesions. We used landmark analysis to exclude severely ill patients dying without staged PCI in an attempt to minimize selection bias between the 2 strategies. Exclusion of patients who had clinical events before the landmark point, however, might underestimate the effect of staged PCI. Also, 90-day landmark analysis might exclude those clinical events related to periprocedural complications of staged PCI. Taking these limitations into account, the possibility that the true effects of staged PCI for residual significant lesions is somewhat different from those in the current observational study, cannot be denied. To evaluate the robust effects of staged PCI strategy, therefore, we need randomized trials allocating those STEMI patients stabilized after primary PCI into either a staged PCI group or a culprit-only PCI group. Second, the limited number of patients receiving multivessel PCI in the acute STEMI setting made it difficult to adequately evaluate the outcome of the acute multivessel PCI strategy. Finally, we did not collect data on non-invasive functional assessment and/or fractional flow reserve measurement for the decision on staged PCI. It is likely that the significance of non-culprit lesions is assessed only on angiography in most cases.

Conclusions

In STEMI patients with MVD who underwent primary PCI, staged PCI strategy for angiographically significant non-culprit lesions was associated with lower 5-year mortality compared with the culprit-only PCI strategy.

Acknowledgments

We appreciate the support and collaboration of the co-investigators participating in the CREDO-Kyoto AMI Registry. We are indebted to the clinical research coordinators for their outstanding effort at data collection.

Conflict of Interest

The authors declare no conflicts of interest.

Source of Funding

The CREDO-Kyoto AMI Registry cohort-2 was funded by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.

Supplementary Files

Supplementary File 1

Appendix S1. Participating Centers and Investigators in the CREDO-Kyoto AMI Registry

Appendix S2. Clinical Research Coordinators

Appendix S3. Clinical Event Committee Members

Supplementary Methods

Table S1. Baseline characteristics vs. PCI strategy

Table S2. Clinical events within 90 days after primary PCI

Table S3. Baseline characteristics of propensity score-matched cohort

Table S4. Angiographic and procedural characteristics of propensity score-matched cohort

Figure S1. Time to first staged percutaneous coronary intervention (PCI) within 90 days from the primary PCI.

Figure S2. Kaplan-Meier event curves for clinical outcome in the propensity score-matched cohort: culprit-only percutaneous coronary intervention (PCI) vs. staged PCI.

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-15-0493

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