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Comparison of Long‐Term Clinical Outcome Between Multivessel Percutaneous Coronary Intervention Versus Infarct‐Related Artery–Only Revascularization for Patients With ST‐Segment–Elevation Myocardial Infarction With Cardiogenic Shock

Originally publishedhttps://doi.org/10.1161/JAHA.119.013870Journal of the American Heart Association. 2019;8:e013870

Abstract

Background

Data are limited regarding long‐term outcomes in patients with ST‐segment–elevation myocardial infarction and multivessel disease presenting with cardiogenic shock according to revascularization strategy. We sought to compare the 3‐year clinical outcomes of patients with ST‐segment‐elevation myocardial infarction multivessel disease with cardiogenic shock and patients with multivessel percutaneous coronary intervention (PCI) and infarct‐related artery (IRA)–only PCI.

Methods and Results

Of 13 104 patients from the nationwide, multicenter, prospective KAMIR‐NIH (Korea Acute Myocardial Infarction Registry––National Institutes of Health) registry, we selected 659 patients with ST‐segment‐elevation myocardial infarction who had concomitant non‐IRA stenosis and presented with cardiogenic shock. The primary outcome was all‐cause death. Multivessel PCI was performed in 260 patients and IRA‐only PCI in 399 patients. At 3 years, patients in the multivessel PCI group had a lower risk of all‐cause death (adjusted hazard ratio, 0.65; 95% CI, 0.45–0.94 [P=0.024]), all‐cause death or MI (adjusted hazard ratio, 0.59; 95% CI, 0.41–0.84 [P=0.004]), and non‐IRA repeat revascularization (adjusted hazard ratio, 0.23; 95% CI, 0.10–0.50 [P<0.001]) than those in the IRA‐only PCI group. The results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. Landmark analysis at 1 year demonstrated that the multivessel PCI group had a lower risk of recurrent MI and non‐IRA repeat revascularization beyond 1 year (log‐rank P=0.030 and P=0.017, respectively) than the IRA‐only PCI group.

Conclusions

In patients with ST‐segment‐elevation myocardial infarction and cardiogenic shock, multivessel PCI was associated with a lower risk of all‐cause death than IRA‐only PCI at 3 years, suggesting potential benefit of non‐IRA revascularization during the index hospitalization to improve long‐term clinical outcomes.

Clinical Perspective

What Is New?

  • In patients with ST‐segment–elevation myocardial infarction multivessel disease complicated with cardiogenic shock, multivessel percutaneous coronary intervention (PCI) was associated with a lower risk of all‐cause death, myocardial infarction, and non–infarct‐related artery repeat revascularization at 3 years than infarct‐related artery–only PCI.

  • The 1‐year landmark analysis showed that there was significantly lower risk of delayed adverse events in patients with multivessel PCI than in an infarct‐related artery–only group for recurrent myocardial infarction and non–infarct‐related artery repeat revascularization.

  • In the multivessel PCI group, patients who underwent complete revascularization presented the most favorable prognosis at 3 years; however, patients who ended with incomplete revascularization showed similar risk of 3‐year all‐cause death and patient‐oriented composite outcome with the infarct‐related artery–only PCI group.

What Are the Clinical Implications?

  • The results of this study support the long‐term benefit of multivessel PCI in patients with ST‐segment–elevation myocardial infarction with multivessel coronary artery disease who progressed to cardiogenic shock.

  • In patients with ST‐segment–elevation myocardial infarction with cardiogenic shock, achieving complete revascularization may be more important than the issue of timing of non–infarct‐related artery PCI in terms of long‐term outcomes.

About 5% to 10% of patients with ST‐segment–elevation myocardial infarction (STEMI) present with cardiogenic shock and the mortality rate of this population is high.1 Considering that up to 80% of patients with cardiogenic shock are known to have multivessel disease,2 it is important to determine an appropriate revascularization strategy for concomitant non–infarct‐related artery (IRA) lesions. European Society of Cardiology guidelines for STEMI have recommended consideration of non‐IRA percutaneous coronary intervention (PCI) during the index procedure in patients with cardiogenic shock as a class IIa recommendation based on expert opinion.3 However, the recent CULPRIT‐SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, the only relevant randomized study on this issue, reported that immediate multivessel PCI increased the risk of 30‐day all‐cause death and new renal replacement therapy compared with IRA‐only PCI.4 This result contributed to the downgrade of routine revascularization of non‐IRA lesions during primary PCI in patients with myocardial infarction (MI) and cardiogenic shock to class III in the most recent European guideline.5

However, our group previously reported that the risk of all‐cause death at 1 year was significantly lower after multivessel PCI than IRA‐only PCI using data from the KAMIR‐NIH (Korea Acute Myocardial Infarction Registry––National Institutes of Health) registry.6 Moreover, difference in mortality according to revascularization strategy disappeared and the risk of rehospitalization for heart failure and repeat revascularization was significantly lower with multivessel PCI than with culprit lesion–only PCI at 1‐year follow‐up of the CULPRIT‐SHOCK trial.7 These results emphasize the need for data on long‐term clinical outcomes beyond 1 year to clarify appropriate revascularization strategy for non‐IRA lesions in patients with STEMI complicated with cardiogenic shock. Therefore, we sought to compare clinical outcomes at 3 years after multivessel PCI versus IRA‐only PCI in patients with STEMI who have cardiogenic shock and multivessel disease.

Methods

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Study Population

We used data from the multicenter, prospective KAMIR‐NIH registry, which is a dedicated registry that enrolled consecutive patients with acute MI from 20 nationwide tertiary centers eligible for primary PCI from November 2011 to December 2015, without applying any criteria for exclusion. Detailed study protocols have been published elsewhere.6, 8 The process of patient selection and the definition of STEMI, multivessel disease, and cardiogenic shock were presented in our previously published article6 as well as in Data S1. In brief, we selected patients with STEMI who had multivessel disease who also presented with cardiogenic shock and underwent primary PCI. Presence of multivessel disease was defined as having additional ≥50% diameter stenosis in at least 1 major non‐IRA or in the left main coronary artery. Cardiogenic shock was defined as systolic blood pressure <90 mm Hg for >30 minutes or the need for supportive management to maintain systolic blood pressure >90 mm Hg, clinical signs of pulmonary congestion, and evidence of impaired end‐organ perfusion with at least 1 of the following: cool extremities, decreased urine output, increased lactic acid level, or altered mental status.9 Complete revascularization was defined as revascularization for any lesion with a diameter stenosis ≥50% in any epicardial coronary artery with a reference vessel diameter ≥2.0 mm by visual estimation.

We excluded patients with a diagnosis of non‐ST‐segment‐elevation myocardial infarction (NSTEMI) and those who arrived after >12 hours from onset of symptom, did not present with cardiogenic shock, underwent thrombolysis before PCI, had single‐vessel disease, underwent suboptimal or failed PCI for IRA, or were lost to follow‐up before 1 year. A total of 659 patients were selected and classified into the multivessel PCI or IRA‐only PCI group (Figure 1). We defined the multivessel PCI group as patients who underwent immediate non‐IRA PCI during the primary PCI or staged non‐IRA PCI within the index hospitalization.

Figure 1.

Figure 1. Study Flow. Study flow of patient selection and follow‐up are presented. IRA indicates infarct‐related artery; KAMIR‐NIH, Korea Acute Myocardial Infarction Registry––National Institutes of Health; NSTEMI, non–ST‐segment–elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST‐segment–elevation myocardial infarction.

The individual ethics committee at each participating center approved the protocol of the KAMIR‐NIH registry. The present study was conducted according to the principles of the Declaration of Helsinki. All enrolled patients provided written informed consent. In cases of patients being unable to consent because of clinical status, a relative was informed and could provide consent on behalf of that patient.

Patient Treatment and Data Management

Patient treatment was performed according to current standard practice. The choice of treatment strategy; type, diameter, and length of stents; and use of medications, intravascular imaging devices, thrombus aspiration, or hemodynamic support devices were left to operator discretion. After PCI, all patients were recommended to take aspirin indefinitely plus clopidogrel or a potent P2Y12 inhibitor, such as prasugrel or ticagrelor, for at least 1 year.

Demographic features and cardiovascular risk factors were collected by patient interviews or review of medical records. During hospitalization, findings of coronary angiography and detailed procedural characteristics of PCI as well as information on discharge medications were collected. Attending physicians followed patients at 6, 12, 24, and 36 months after discharge. The data were completed by telephone interview if patients did not visit on their scheduled day of follow‐up. Using a web‐based case report form in the internet‐based Clinical Research and Trial management system (iCReaT), independent clinical research coordinators collected all baseline data and clinical events up to 3 years of follow‐up.

Study End Points

The primary outcome was all‐cause death, and the secondary end point was all‐cause death or recurrent MI at 3 years. Secondary end points also included cardiac death, non‐IRA repeat revascularization, any repeat revascularization, definite or probable stent thrombosis, and patient‐oriented composite outcome (a composite of all‐cause death, any MI, or any repeat revascularization) at 3 years. All deaths were considered cardiac unless an undisputed noncardiac cause was present. Recurrent MI was defined as the recurrence of symptoms or the presence of ECG changes in association with a rise in cardiac biomarker levels above the upper limit of normal, and periprocedural MI was not included as a clinical outcome. Clinically driven revascularization that occurred after discharge from the index hospitalization was coded as a repeat revascularization event, and any planned revascularization was not considered as a clinical event. All end points were defined according to the definitions of the Academic Research Consortium.10, 11 All clinical events were evaluated by an independent event adjudicating committee. The definition of study end points and the process of event adjudication are described in the previous publication of KAMIR‐NIH investigators.8

Statistical Analysis

Details of the statistical analysis are presented in Data S1. Categorical variables were presented as numbers and relative frequencies (percentages) and were compared using chi‐square test. Continuous variables were expressed as mean±SD or median (quartile 1–quartile 3), according to whether they were normally distributed, and were compared using the independent sample t test or Mann–Whitney test, as appropriate. Cumulative incidence of events at 3 years was calculated based on Kaplan‐Meier censoring estimates, and comparison of clinical outcomes between the multivessel PCI and IRA‐only PCI groups was performed with the log‐rank test. For the landmark analysis, patients at risk were reset to those who were free from events at the beginning of the landmark time point, which was 1 year after the index procedure in this analysis.

Sensitivity analyses were performed to adjust for confounding factors. First, a multivariable Cox regression model was used. Covariates included in the multivariable model were selected if they were significantly different between the 2 groups or had predictive values, which are listed in Data S1. The assumption of proportionality was assessed graphically by the log‐minus‐log plot, and Cox proportional hazard models for all clinical outcomes satisfied the proportional hazards assumption. For the landmark analysis, a Cox proportional hazard model with the assumption of piecewise proportionality according to the landmark time point was used.

Second, the propensity score–matched and inverse probability–weighted (IPW) Cox proportional hazard regression were performed. All available covariates were included in the logistic regression model to generate propensity scores, precisely following the recommendations of analysis using propensity score.12 For the propensity score matching, a 1:1 matching process without replacements was performed by a greedy algorithm with a caliper width of 0.4 SDs, yielding 233 patients in the multivessel PCI group matched with 233 controls in the IRA‐only PCI group. For the IPW adjustment, inverse of propensity score was adjusted in Cox proportional hazard regression model. Balance between the 2 groups after propensity score matching or IPW adjustment was assessed by percent standardized mean differences of all covariates. Percent standardized mean differences after propensity score matching or IPW adjustment were within ±10% across all matched covariates, demonstrating successful balance achievement between comparative groups (Table S1).

We established a multivariable Cox proportional hazard model to identify independent predictors of 3‐year all‐cause death and all‐cause death or MI. C‐statistics with 95% CIs were calculated to validate the discriminant function of the model. Comparison of the primary outcome according to the various exploratory subgroups was followed. In all analysis, the participating centers were included as random effects. All probability values were 2‐sided and P values <0.05 were considered statistically significant.

Results

Baseline Characteristics

We analyzed the 3‐year clinical outcomes of 659 patients with STEMI who had cardiogenic shock and concomitant non‐IRA stenosis according to the PCI strategy (260 received multivessel PCI and 399 IRA‐only PCI). Follow‐up to 3 years was completed in 98.9% of the total patients with a median follow‐up duration of 1066 days. Baseline clinical, lesion, and procedural profiles are described in Tables 1 and 2. One third of the patients with STEMI who had multivessel disease with cardiogenic shock experienced cardiac arrest at the visit, and the proportion of the left main artery as a culprit vessel was about 10%. Second‐generation drug‐eluting stents were implanted in 87.9% of patients, and 26.7% received at least 1 type of hemodynamic support including intra‐aortic balloon pump or percutaneous cardiopulmonary support. Of patients in the multivessel PCI group, 157 patients (60.4%) underwent non‐IRA PCI immediately after primary PCI during the index procedure, and 103 (39.6%) did staged non‐IRA PCI during the index hospitalization. Complete revascularization was achieved in 171 patients (65.8%).

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Table 1. Baseline Clinical Characteristics

Total Population (N=659)Multivessel PCI (n=260)IRA‐Only PCI (n=399)P Value
Demographics
Age, y66.9±12.466.2±11.967.3±12.80.266
Age >65 y384 (58.3)150 (57.7)234 (58.6)0.808
Men490 (74.4)191 (73.5)299 (74.9)0.672
BMI, kg/m223.5±3.223.6±3.123.4±3.20.396
Initial presentation
Killip class 4300 (45.6)110 (42.5)190 (47.6)0.195
Cardiac arrest236 (35.8)85 (32.7)151 (37.8)0.178
Process of care index
Symptom onset‐to‐balloon time, h3.4 (2.1–7.2)3.4 (2.1–8.5)3.5 (2.0–6.8)0.119
Door‐to‐balloon time, min62.0 (48.0–82.0)62.5 (47.0–84.0)62.0 (49.0–81.0)0.817
Cardiovascular risk factors
Hypertension354 (53.7)136 (52.3)218 (54.6)0.558
DM270 (41.0)107 (41.2)163 (40.9)0.939
DM on insulin20 (3.0)5 (1.9)15 (3.8)0.179
Dyslipidemia308 (46.7)122 (46.9)186 (46.6)0.939
Chronic kidney disease244 (37.0)87 (33.5)157 (39.3)0.126
History of MI53 (8.0)17 (6.5)36 (9.0)0.252
Previous CHF admission15 (2.3)2 (0.8)13 (3.3)0.036
Previous history of CVA57 (8.6)20 (7.7)37 (9.3)0.480
Current smoking250 (37.9)105 (40.4)145 (36.3)0.296
LVEF, %45.9±13.044.3±13.247.0±12.70.013
Peak cardiac enzyme levels
CK‐MB, ng/mL202.4±247.5216.3±319.1193.4±186.60.295
Troponin I, ng/mL85.9±133.195.4±158.679.2±111.80.189
Medications at discharge
Aspirin653 (99.1)257 (98.8)396 (99.2)0.595
Clopidogrel470 (71.3)176 (67.7)294 (73.7)0.096
Prasugrel60 (9.1)32 (12.3)28 (7.0)0.021
Ticagrelor119 (18.1)48 (18.5)71 (17.8)0.828
ACEI or ARB402 (61.0)163 (62.7)239 (59.9)0.473
β‐Blocker430 (65.3)182 (70.0)248 (62.2)0.039
Statin498 (75.6)204 (78.5)294 (73.7)0.163
Oral anticoagulant19 (2.9)11 (4.2)8 (2.0)0.095

Values are described as numbers (percentage), mean±SD, or median (quartile 1–quartile 3). Categorical variables were compared using chi‐square test. Continuous variables were compared using independent sample t test or Mann–Whitney test, as appropriate. ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CHF, congestive heart failure; CK‐MB, creatine kinase‐MB; CVA, cerebrovascular accident; DM, diabetes mellitus; IRA, infarct‐related artery; LVEF, left ventricular ejection fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention.

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Table 2. Baseline Lesion‐ and Procedure‐Related Profiles

Total Population (N=659)Multivessel PCI (n=260)IRA‐Only PCI (n=399)P Value
Culprit lesion profiles
Location
Left main artery62 (9.4)39 (15.0)23 (5.8)0.001
LAD238 (36.1)91 (35.0)147 (36.8)
LCX74 (11.2)29 (11.2)45 (11.3)
RCA285 (43.2)101 (38.8)184 (46.1)
Type B2/C lesiona595 (90.3)233 (89.6)362 (90.7)0.638
Small vesselb158 (25.5)64 (25.5)94 (25.5)0.995
Long lesionc267 (43.1)102 (40.6)165 (44.7)0.314
Overall lesion profiles
Left main artery disease87 (13.2)47 (18.1)40 (10.0)0.003
3‐Vessel disease221 (33.5)88 (33.8)133 (33.3)0.892
Procedural characteristics
Transradial approach96 (14.6)28 (10.8)68 (17.0)0.055
Glycoprotein IIb/IIIa inhibitor use154 (23.4)64 (24.6)90 (22.6)0.542
Thrombus aspiration206 (31.5)73 (28.4)133 (33.4)0.177
IRA treatment
Bare metal stent38 (5.8)13 (5.0)25 (6.3)0.190
First‐generation DES4 (0.6)1 (0.4)3 (0.8)
Second‐generation DES579 (87.9)237 (91.2)342 (85.7)
Plain balloon angioplasty38 (5.8)9 (3.5)29 (7.3)
Non‐IRA treatment
Bare metal stent7 (2.7)
First‐generation DES0 (0.0)
Second‐generation DES219 (84.2)
Plain balloon angioplasty34 (13.1)
Total number of implanted stents1.55±0.872.24±0.831.10±0.54<0.001
Pre‐PCI TIMI flow in culprit lesion
0423 (64.2)157 (60.4)266 (66.7)0.203
166 (10.0)26 (10.0)40 (10.0)
2 or 3170 (25.8)77 (29.6)93 (23.3)
IVUS during PCI120 (18.2)52 (20.0)68 (17.0)0.336
OCT during PCI12 (1.8)2 (0.8)10 (2.5)0.103
Hemodynamic support device176 (26.7)72 (27.7)104 (26.1)0.644
IABP155 (23.5)65 (25.0)90 (22.6)0.470
PCPS/ECMO52 (7.9)22 (8.5)30 (7.5)0.661
Completeness of multivessel PCI
Complete revascularization171 (65.8)
Incomplete revascularization89 (34.2)
Timing of non‐IRA PCI
Immediate PCI during index procedure157 (60.4)
Staged PCI before discharge103 (39.6)
Periprocedural safety
New renal replacement therapy during index hospitalization22 (3.3)9 (3.5)13 (3.3)0.887
New renal replacement therapy at 1 y45 (6.8)17 (6.5)28 (7.0)0.812

Values are described as numbers (percentages) or mean±SD. Categorical variables were compared using chi‐square test. Continuous variables were compared using independent sample t test or Mann–Whitney test, as appropriate. DES indicates drug‐eluting stent; ECMO, extracorporeal membrane oxygenation; IABP, intra‐aortic balloon pump; IVUS, intravascular ultrasound; IRA, infarct‐related artery; LAD, left anterior descending artery; LCX, left circumflex artery; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; PCPS, percutaneous cardiopulmonary support; RCA, right coronary artery; TIMI, Thrombolysis in Myocardial Infarction.

aType B2 or C lesions according to American College of Cardiology/American Heart Association classification.

bSmall vessel denotes lesion with reference diameter ≤2.75 mm.

cLong lesion denotes lesion with length ≥28 mm.

Comparison of 3‐Year Outcomes According to Treatment Strategy

At 3 years, the risk of all‐cause death was significantly lower in the multivessel PCI group than in the IRA‐only PCI group (24.3% versus 37.7%) (adjusted hazard ratio, 0.65; 95% CI, 0.45–0.94 [P=0.024]). All‐cause death or MI and patient‐oriented composite outcome also occurred less frequently with multivessel PCI than with IRA‐only PCI (24.4% versus 40.3%) (adjusted hazard ratio, 0.59; 95% CI, 0.41–0.84 [P=0.004]) and 31.8% versus 50.8% (adjusted hazard ratio, 0.57; 95% CI, 0.44–0.73 [P<0.004]), respectively (Figure 2).

Figure 2.

Figure 2. Cumulative incidence of clinical outcomes at 3 years. Kaplan‐Meier curves with cumulative hazards of (A) all‐cause death, (B) all‐cause death or recurrent myocardial infarction (MI), (C) recurrent MI, (D) non–infarct‐related artery (IRA) repeat revascularization, (E) any repeat revascularization, and (F) patient‐oriented composite outcome (POCO), compared according to the percutaneous coronary intervention (PCI) strategy.

In addition to the composite end point, multivessel PCI was favored in most of the secondary end points such as cardiac death, recurrent MI, or any or non‐IRA repeat revascularization; however, the risk of definite or probable stent thrombosis was not different between the 2 groups (Table 3). Consistent results were found in sensitivity analyses including multivariable Cox regression, propensity score matching, and IPW analysis. In the landmark analysis at 1 year, the risk of all‐cause death tended to be lower with multivessel PCI than IRA‐only PCI, yet statistical significance was not achieved. The risk of all‐cause death or MI, recurrent MI, and non‐IRA repeat revascularization beyond 1 year were significantly lower in the multivessel PCI group than in the IRA‐only PCI group (Figure 3).

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Table 3. Comparison of 3‐Year Clinical Outcomes According to Treatment Strategy

Multivessel PCI (n=260)IRA‐Only PCI (n=399)UnadjustedMultivariable‐AdjustedPropensity Score–MatchedIPW‐Adjusted
HR (95% CI)P ValueHR (95% CI)P ValueHR (95% CI)P ValueHR (95% CI)P Value
All‐cause death24.3% (67)37.7% (155)0.60 (0.45–0.80)<0.0010.65 (0.45–0.94)0.0240.66 (0.47–0.91)0.0110.63 (0.48–0.84)0.002
Cardiac death17.5% (50)29.2% (126)0.56 (0.40–0.77)<0.0010.65 (0.41–1.03)0.0690.61 (0.42–0.89)0.0100.55 (0.40–0.77)0.001
Recurrent MI2.9% (7)7.3% (19)0.47 (0.20–1.12)0.0900.50 (0.20–1.26)0.1420.46 (0.18–1.15)0.0950.42 (0.18–0.97)0.042
Any repeat revascularization11.9% (24)20.2% (53)0.57 (0.35–0.92)0.0200.52 (0.31–0.87)0.0130.44 (0.25–0.75)0.0030.53 (0.33–0.85)0.008
Non‐IRA repeat revascularization3.9% (8)14.4% (37)0.27 (0.13–0.58)0.0010.23 (0.10–0.50)<0.0010.18 (0.07–0.43)<0.0010.24 (0.12–0.49)<0.001
Definite or probable stent thrombosis0.5% (1)1.5% (4)0.32 (0.04–2.88)0.3100.46 (0.03–6.78)0.5720.21 (0.02–1.89)0.1640.28 (0.03–2.36)0.243
Readmission as a result of heart failure4.8% (10)7.1% (18)0.72 (0.33–1.55)0.3960.79 (0.31–2.03)0.6192.73 (1.09–6.84)0.0321.09 (0.45–2.61)0.852
All‐cause death or MI24.4% (68)40.3% (165)0.57 (0.43–0.75)<0.0010.59 (0.41–0.84)0.0040.60 (0.44–0.83)0.0020.59 (0.44–0.78)<0.001
Patient‐oriented composite outcomea31.8% (86)50.8% (203)0.57 (0.44–0.73)<0.0010.55 (0.40–0.75)<0.0010.54 (0.40–0.71)<0.0010.56 (0.44–0.72)<0.001

The cumulative incidence of clinical outcomes is presented as Kaplan‐Meier estimates during a median follow‐up of 1066.0 days. The numbers in parentheses in the columns of 2 groups indicate the number of patients with specific events. Multivariable Cox proportional hazard regression model, propensity score–matched cohort, and inverse probability of treatment weighting method were used to adjust for baseline differences between comparative groups. Covariates included in the multivariable model are type of treatment strategy, participating center, age older than 65 years, sex, Killip class at initial presentation, symptom onset‐to‐balloon time, door‐to‐balloon time, diabetes mellitus, dyslipidemia, chronic kidney disease, history of myocardial infarction (MI), history of cerebrovascular accident, current smoking, left ventricular dysfunction with ejection fraction <50%, left main artery or left anterior descending artery as a culprit vessel, left main artery disease, 3‐vessel disease, small vessel ≤2.75 mm, long lesion ≥28 mm, and type B2 or C lesion according to the American College of Cardiology/American Heart Association classification. HR indicates hazard ratio; IPW, inverse probability weighting; IRA, infarct‐related artery; PCI, percutaneous coronary intervention.

aPatient‐oriented composite outcome was defined as a composite of all‐cause death, recurrent MI, or any repeat revascularization.

Figure 3.

Figure 3. Landmark analysis of clinical outcomes from 1 year. Landmark analysis from 1 year of composite end points and individual outcomes, (A) all‐cause death, (B) all‐cause death or recurrent myocardial infarction (MI), (C) recurrent MI, (D) non–infarct‐related artery (IRA) repeat revascularization, (E) any repeat revascularization, and (F) patient‐oriented composite outcome (POCO). PCI indicates percutaneous coronary intervention.

In analysis according to the completeness of revascularization after multivessel PCI, the incomplete multivessel PCI group showed a “catch‐up” phenomenon in both all‐cause death and all‐cause death or MI, while those achieving complete revascularization had sustained benefit in all‐cause death and all‐cause death or MI without any catch‐up phenomenon until 3 years (Figure S1). In an exploratory subgroup analysis, there was no significant interaction across various subgroups, and consistent trends favoring multivessel PCI in terms of all‐cause death than IRA‐only PCI were observed in all subgroups (Figure S2).

Independent Predictors of All‐Cause Death and All‐Cause Death or MI

A multivariable Cox proportional hazards model showed that multivessel PCI was a significant and negative independent predictor of all‐cause death (hazard ratio, 0.555; 95% CI, 0.415–0.741 [P<0.001]) and all‐cause death or MI (hazard ratio, 0.522; 95% CI, 0.392–0.694 [P<0.001]) at 3 years. Age, chronic kidney disease, diabetes mellitus, left main or left anterior descending artery as a culprit vessel, presence of left main disease, and 3‐vessel disease were identified as independent predictors of all‐cause death and all‐cause death or MI (Table 4).

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Table 4. Independent Predictors for Clinical Outcomes at 3 Years

HR95% CIP value
All‐cause death
Multivessel PCI (IRA‐only PCI group as a reference)0.560.42 to 0.74<0.001
Age >65 y3.022.17 to 4.21<0.001
Left main or LAD as a culprit vessel2.201.65 to 2.94<0.001
Chronic kidney disease1.851.41 to 2.43<0.001
Presence of left main disease1.691.16 to 2.450.006
3‐Vessel disease1.441.07 to 1.930.016
All‐cause death or MI
Multivessel PCI (IRA‐only PCI group as a reference)0.520.39 to 0.69<0.001
Age >65 y2.521.85 to 3.43<0.001
Left main or LAD as a culprit vessel2.191.65 to 2.90<0.001
Chronic kidney disease1.841.41 to 2.40<0.001
Presence of left main disease1.681.17 to 2.420.005
3‐Vessel disease1.411.06 to 1.880.019

Hazard ratios (HRs) and their 95% CIs were calculated by multivariable Cox regression analysis. The Harrell's C‐index of the multivariable Cox proportional hazards model was 0.746 (95% CI, 0.713–0.780) for all‐cause death and 0.728 (95% CI, 0.696–0.760) for all‐cause death or myocardial infarction (MI). IRA indicates infarct‐related artery; LAD, left anterior descending artery; PCI, percutaneous coronary intervention.

Discussion

The current study compared 3‐year clinical outcomes after multivessel PCI versus IRA‐only PCI among patients with STEMI multivessel disease complicated with cardiogenic shock. The main findings are as follows. First, the risk of all‐cause death was significantly lower in the multivessel PCI group than in the IRA‐only PCI group at 3 years, which was consistent in various sensitivity analyses with confounder adjustment. In addition, the risk of recurrent MI and non‐IRA repeat revascularization was also significantly lower with multivessel PCI than with IRA‐only PCI. Second, landmark analysis at 1 year showed that there was significantly lower risk of delayed adverse events in the multivessel PCI group than in the IRA‐only PCI group in terms of recurrent MI and non‐IRA repeat revascularization. Third, among patients in the multivessel PCI group, those undergoing complete revascularization had the most favorable prognosis at 3 years; however, those with incomplete revascularization showed late catch‐up phenomenon and similar risk of all‐cause death compared with the IRA‐only PCI group. Fourth, an exploratory subgroup analysis showed consistent trends favoring multivessel PCI regarding all‐cause death compared with IRA‐only PCI.

Current Evidence and Need for Long‐Term Data

In patients with STEMI who have cardiogenic shock, multivessel disease is common and is well known to have a detrimental impact on short‐ and long‐term prognosis.2 Results of the recently reported PRAMI (Preventive Angioplasty in Acute Myocardial Infarction), CvLPRIT (Complete Versus Lesion‐Only Primary PCI Trial), DANAMI‐3‐PRIMULTI (Primary PCI in Patients With ST‐elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), and Compare‐Acute (Fractional Flow Reserve Guided Primary Multivessel Percutaneous Coronary Intervention to Improve Guideline Indexed Actual Standard of Care for Treatment of ST‐elevation Myocardial Infarction in Patients With Multivessel Coronary Disease) trials demonstrated a significant benefit of multivessel PCI in hemodynamically stable patients with STEMI and multivessel disease.13, 14, 15, 16 However, these trials excluded patients with cardiogenic shock, and evidence from observational studies was also scarce. In the case of cardiogenic shock, controversy exists regarding the risks/benefits of multivessel PCI, such as concerns about possible procedure‐related complications or contrast‐induced nephropathy versus expectations for physiologic benefit through myocardial perfusion and recovery.17, 18

In this context, the randomized CULPRIT‐SHOCK trial was conducted, which reported that the risk of 30‐day all‐cause death or new renal replacement therapy was higher in the immediate multivessel PCI group than in the IRA‐only PCI group.4 Similarly, the BCCR (British Columbia Cardiac Registry) investigators recently reported that IRA‐only PCI was associated with lower mortality in patients with acute MI who had cardiogenic shock, particularly in the STEMI subgroup.19 Based primarily on the 30‐day results from the CULPRIT‐SHOCK trial, the latest update of the European guideline downgraded the immediate multivessel PCI for patients with acute MI multivessel disease with cardiogenic shock to a class III recommendation.5 However, a subsequent 1‐year report of the CULPRIT‐SHOCK trial showed slightly different results from the 30‐day results, and encouraged us to reconsider the possibility of long‐term benefit of multivessel PCI in these patients. At 1‐year follow‐up, the difference in the primary end point (all‐cause death and new renal replacement therapy) between the 2 groups lost its statistical significance, while the rate of rehospitalization for heart failure and repeat revascularization was significantly lower in the multivessel PCI group.7 Moreover, previous 1‐year results from the KAMIR‐NIH registry presented a significantly lower risk of all‐cause death and patient‐oriented composite outcome in the multivessel PCI group compared with the IRA‐only PCI group.6 This result indirectly supports the possibility of long‐term benefits of multivessel PCI to maximize left ventricular function recovery and to minimize the risk of future repeat revascularization. However, to date, there has been no evidence presenting long‐term outcomes of patients with STEMI multivessel disease complicated with cardiogenic shock, according to treatment strategy. In this regard, we sought to analyze 3‐year clinical outcomes of the KAMIR‐NIH registry, a largescale data set that exclusively analyzed patients with STEMI who had cardiogenic shock and concurrent multivessel disease.

Long‐Term Prognosis of Multivessel PCI in Patients With Multivessel Disease and Cardiogenic Shock

In the present study, the risk of all‐cause death at 3 years after the index hospitalization was significantly lower in the multivessel PCI group than the IRA‐only PCI group. Although it is difficult to explain the exact mechanism, revascularization for non‐IRA might prevent recurrent MI and, in turn, reduce mortality. Landmark analysis at 1 year showed that the risk of recurrent MI was significantly lower in the multivessel PCI group than the IRA‐only PCI group. In addition, when comparing 3‐year clinical outcomes among IRA‐only PCI, multivessel PCI with incomplete revascularization, and multivessel PCI with complete revascularization, patients achieving complete revascularization showed the most favorable prognosis, while those with incomplete revascularization had risk of all‐cause death and all‐cause death or MI similar to the IRA‐only PCI group. These results are in line with the previous PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) trial, which showed more than half of clinical events in patients with acute coronary syndrome were related with non‐IRA stenosis.20 The above results imply that multivessel PCI might be associated with lower risk of future adverse events than IRA‐only PCI. Furthermore, the above results might be intuitive, considering the results from previous trials that demonstrated consistent benefit of multivessel PCI compared with IRA‐only PCI in hemodynamically stable patients with STEMI.13, 14, 15, 16

It should be noted that there are some differences in study protocols and the definition of comparative groups, which may explain the discrepancies between the current results and those from the CULPRIT‐SHOCK trial or the BCCR.4, 7, 19 First, the CULPRIT‐SHOCK trial and the BCCR registry analyzed both patients with STEMI and NSTEMI, not exclusively patients with STEMI. Second, in the CULPRT‐SHOCK trial, the immediate multivessel PCI was mandated even for the chronic total occlusion in non‐IRA, which accounted for 25% of the study population. Third, in the CULPRIT‐SHOCK trial, staged non‐IRA PCI was strongly recommended in the IRA‐only PCI group, and ≈30% of the IRA‐only PCI group was treated with the multivessel PCI strategy. Conversely, the multivessel PCI group used in the present study included both immediate or staged non‐IRA PCI within the same admission period. All previous trials, except the CULPRIT‐SHOCK trial, classified staged non‐IRA PCI as multivessel PCI or complete revascularization.13, 14, 15, 16

Study Limitations

There are some limitations to be discussed. First, we could not prove causality because of the observational nature of the registry data. Second, although confounding factors were thoroughly adjusted by various statistical methods, it was impossible to exclude the effects of unmeasured confounders, such as experience in patient management or procedure volume of participating centers. Third, the KAMIR‐NIH registry was a clinical database that was not supplemented or linked by administrative data. Fourth, in consideration of possible uncontrolled bias in the decision of staged non‐IRA revascularization, the prognosis of multivessel PCI by the timing of PCI could not be analyzed. However, it should be noted that timing of non‐IRA PCI might be a clinical decision according to patient status, and therefore one uniform recommendation cannot be made considering diverse clinical situations. Fifth, outcomes such as recovery of left ventricular function, procedural complications, and long‐term change of renal function were not included in the follow‐up protocol. Finally, there was a lack of information regarding the type or dose of contrast agents and the procedure times.

Conclusions

In patients with STEMI multivessel disease complicated with cardiogenic shock, multivessel PCI was associated with a lower risk of all‐cause death, recurrent MI, and non‐IRA repeat revascularization at 3 years than IRA‐only PCI. The multivessel PCI group showed a lower risk of recurrent MI and non‐IRA repeat revascularization beyond 1 year compared with the IRA‐only PCI group. The current results support that multivessel PCI in patients with STEMI who have multivessel disease and complicated with cardiogenic shock might be associated with lower risk of future adverse events than IRA‐only PCI.

Sources of Funding

This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention (2016‐ER6304‐01).

Disclosures

None.

Footnotes

*Correspondence to: Myung Ho Jeong, MD, PhD, Department of Cardiology, Chonnam National University Hospital, 42 Jebong‐ro, Dong‐gu, Gwangju 61469, Republic of Korea. Email: and Joo‐Yong Hahn, MD, PhD, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon‐ro, Gangnam‐gu, Seoul, 06351, Republic of Korea. Email:

Dr Joo Myung Lee and Dr Rhee contributed equally to this work.

A complete list of the KAMIR Investigators can be found in the Appendix.

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