Is coronary multivessel disease in acute myocardial infarction patients still associated with worse clinical outcomes at 1‐year?

Abstract Background ST‐elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) are associated with a worse prognosis. However, few comparisons are available according to coronary status in the era of modern reperfusion and optimized secondary prevention. Hypothesis We hypothesized that the difference in prognosis according to number of vessel disease in STEMI patients has reduced. Methods All consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) within 24 h of symptoms onset between January 1, 2014 and June 30, 2016 enrolled in the CRAC (Club Régional des Angioplasticiens de la région Centre) France PCI registry were analyzed. Baseline characteristics, management, and outcomes at 1‐year were analyzed according to coronary status (one‐, two‐, and three‐VD). Results A total of 1886 patients (mean age 62.2 ± 14.0 year; 74% of male) were included. Patients with MVD (two or three‐VD) represented 53.7%. They were older with higher cardiovascular risk factor profile. At 1 year, the rate of major adverse cardiovascular events (MACE, defined as all‐cause death, stroke or re‐MI) was 10%, 12%, and 12% in one‐, two, and three‐VD respectively (p = .28). In multivariable adjusted Cox proportional hazard regression model, two‐ and three‐VD were not associated with higher rate of MACE compared to patients with single VD (HR, 1.09; 95%CI 0.76–1.56 for two‐VD; HR, 0.74; 95%CI 0.48–1.14 for three‐VD). Conclusions MVD still represents an important proportion of STEMI patients but their prognoses were not associated with worse clinical outcomes at 1‐year compared with one‐VD patients in a modern reperfusion area and secondary medication prevention.

outcomes at 1-year were analyzed according to coronary status (one-, two-, and three-VD).
Results: A total of 1886 patients (mean age 62.2 ± 14.0 year; 74% of male) were included. Patients with MVD (two or three-VD) represented 53.7%. They were older with higher cardiovascular risk factor profile. At 1 year, the rate of major adverse cardiovascular events (MACE, defined as all-cause death, stroke or re-MI) was 10%, 12%, and 12% in one-, two, and three-VD respectively (p = .28). In multivariable adjusted Cox proportional hazard regression model, two-and three-VD were not associated with higher rate of MACE compared to patients with single VD (HR, 1.09; 95%CI 0.76-1.56 for two-VD; HR, 0.74; 95%CI 0.48-1.14 for three-VD).
Conclusions: MVD still represents an important proportion of STEMI patients but their prognoses were not associated with worse clinical outcomes at 1-year compared with one-VD patients in a modern reperfusion area and secondary medication prevention. (MVD) represents between 40% and 65% of cases. [1][2][3][4] The primary objective of percutaneous coronary intervention (PCI) in these patients is to restore epicardial flow in the culprit vessel and normalize myocardial perfusion. 1 Revascularization of non-culprit lesion is still debated. However, the pathophysiological process of coronary artery disease (CAD) in myocardial infarction (MI) is not limited to the culprit vessel and MVD in STEMI patients is usually associated with worse clinical outcome including higher mortality compared with patients with single-VD. [1][2][3][4] Several sources, including registries specific to acute myocardial infarction (AMI) and large administrative or billing databases, have shown a decrease in mortality in patients with STEMI over the past 30 years. [5][6][7][8][9][10][11][12][13][14] This decline is attributed to several factors (i.e., increased use and improved delivery of reperfusion therapy, in particular primary PCI, temporal changes in patient population characteristics over the period, increased use and improved delivery of recommended secondary prevention …). [5][6][7][8][9][10][11][12][13][14] To our knowledge, the impact of MVD on clinical outcomes in STEMI patients has not been assessed specifically after these changes.
The aim of our study is to assess the impact of MVD on major adverse cardiovascular events (MACE) at 1-year in a modern reperfusion area and secondary medication prevention using the CRAC (Club Régional des Angioplasticiens de la région Centre) France PCI registry.

| Study population
The CRAC registry, created in 2014, brings together the six interventional cardiology centers of the Centre Val de Loire region and integrated the Clermont Ferrand University Hospital since 2016 to become the CRAC-France PCI registry. It is an observational prospective multicenter registry, which includes all patients undergoing coronary angiography or coronary angioplasty in each participant center. The methods used for this registry have been detailed previously. 15,16 For the present analysis, we enrolled all consecutive STEMI patients undergoing PCI within 24 h of symptoms onset between January 1, 2014 and June 30, 2016 in the six ICCs which had been part of the CRAC registry (n = 1886). One ICC was excluded because of incomplete data. Non-culprit lesion was defined as ≥50% diameter stenosis by visual estimate in at least one non-infarct related vessel.
Patient characteristics, management, and outcomes were analyzed according to coronary status (i.e. one-, two-, vs. three-VD). To define CAD extent, all three coronary arteries were assigned one point each and two points for left main coronary artery (LMCA) whatever the status of left anterior descending and left circumflex, resulting in a maximum score of 3 (i.e., 3-VD) in patients without a history of coronary artery bypass grafting (CABG). Patients with previous CABG were considered as three-VD (n = 25). Multivessel CAD was defined as 2-or 3-VD. Complete myocardial revascularization was considered in our analyses if the additional procedure was performed before discharge or during the first 3 months after index event. Complete myocardial revascularization was defined by successful PCI of all nonculprit lesion(s) (i.e., restoration of blood supply to the myocardium).
The primary endpoint of the study was a composite of MACE at 1-year defined as all-cause death, re-MI, or stroke.

| Data collection
The anonymous database includes up to 150 variables per procedure with hospital follow-up data and at 1 year for any coronary angioplasty and pre-hospital data for STEMI <24 h. 15

| Ethical consideration
The study was conducted according to contemporary clinical prac-

| Statistical analysis
Continuous variables are reported as means (SDs) or medians and interquartile ranges (IQR), when appropriate. Discrete variables are described as counts and percentages. Groups were compared by analysis of variance for continuous variables and χ 2 (or Fisher exact tests) for discrete variables. Hazard ratios (HR) are presented with their 95% confidence intervals (CI). Survival curves were estimated using the Kaplan Meier estimators and compared using log rank tests. The rates of MACE at 1-year were analyzed according to number of VD, and the impact of MVD (i.e., two-or three-VD) was compared using a multivariate backward stepwise Cox analysis with a threshold of 0.10 for variable elimination, among the different risk groups. Variables included in the final models were selected ad hoc, based on their physiological relevance and potential to be associated with outcomes;  Figure S1 shows a flow chart for patient recruitment. Briefly, out of 11 883 patients undergoing PCI included in the CRAC-France PCI registry over the period, 1886 STEMI ≤24 h patients treated by PCI with available medical information were selected for the present analysis.

| Patient characteristics
The mean age of the population was 62.6 ± 14.0 years (74% of male).
MVD represents 53.7% of patients. Patient characteristics are presented in Table 1 according to coronary status (i.e. one-, two-, or three-VD). Overall, cardiovascular risk-profile progressively increased from patients with one-VD to three-VD. Patients with MVD were older with more risk-factors (except for smoking status) and co-morbidities. They had more previous MI and myocardial revascularization.

| In-hospital management and duration of dual antiplatelet therapy
All patients had an invasive strategy and were referred to a cardiac catheterization laboratory. Coronary angiogram showed that the site of the culprit lesion differed according to coronary status (mainly in the left anterior descending artery for patients with one-VD; and, mainly in the right coronary artery for patients with MVD) ( Table 2).
Patients with MVD had more diffuse CAD including longer lesions with smaller diameters. The Syntax score gradually increased between patients with one-VD to three-VD (one-VD: 8.9 ± 5.9; two-VD: 13.0 ± 7.9; three-VD: 19.0 ± 10.7, p < .001). The rates of TIMI score 0/1 of the culprit lesion before primary PCI was similar in all groups.
Procedural characteristics are detailed in Table 2. No difference was observed related to vascular approach and the size of the sheath according to all groups. Primary PCI was performed in 98% of the population. Thrombus aspiration was mainly used in patient with one-VD. Drug-eluting stents were used similarly in all groups, but the number of stents implanted was higher in patients with MVD. Proportion of PCI success was similar in all groups (93% in overall population) as was the rate of TIMI score 2/3 post-PCI (95% in overall population).
Complete myocardial revascularization was performed preferentially before discharge in 26% and 30% of patients with two-and three-VD respectively. Finally, the quantity of contrast and radiation exposure was higher in MVD patients.
Antithrombotic treatment used before admission and medications prescription at discharge are given in Table S1. The choice of antithrombotic treatment (i.e., antiplatelet and anticoagulant) did not dif- Finally, duration of dual antiplatelet therapy after AMI was mainly ≥12 months whatever the coronary status ( Figure S2).

| DISCUSSION
The main findings of this study are that STEMI with MVD currently represents approximately 50% of patients admitted to a cardiac cathe-  3.1% in complete revascularization strategy to 6.2% in culprit-lesiononly PCI. 21 These data suggest that the prognosis of MVD in STEMI patients has changed over the period and, now it is probably close to that of patients with single-VD. In our main analysis, the rate of MACE at 1-year did not differ according to coronary status after adjustment.

| Management of STEMI with MVD
Primary PCI is the preferred reperfusion strategy in patients with STEMI within 12 h of symptom onset. 22 MVD is commonly reported (in approximately 50%) in this population as observed in our study (53.7%). A series of successful clinical trials have proven the improved survival and lower morbidity with complete myocardial revascularization compared to culprit-lesion-only PCI in STEMI patients with MVD. [17][18][19][20][21] This has led to very consistent global treatment recommendations.
Therefore policies of complete myocardial revascularization have increased over the last 10 years even the timing is conflicting. 14,22 In addition, our data show that patients with MVD received more aggressive secondary medication prevention at discharge and the proportion of DAPT at 1 year was numerically higher in this population. 1,22 This represents certainly an important point to explain our results. Finally, the use of new generation drug-eluting stents associated with new P2Y12 inhibitors can reduce complications of PCI and improve the prognosis of these patients. 22

| Limitations
As in any observational study, there are limitations to our analysis. Only STEMI ≤24H patients admitted to a cardiac catheterization laboratory were included, which represents a selection bias. Several data are missing in the database to better define the study groups such as atrial fibrillation (AF). Recent data have shown that patients with AF have generally less severe CAD compared to non-AF ones. 23 In addition, the use of secondary medication prevention are only available during the first 24 h. Finally, the clinical follow-up duration is limited, and we cannot exclude that the prognosis will be similar in all groups after 1 year.

| CONCLUSIONS
MVD in STEMI patients still represents half of the patients despite a substantial change in the patient risk profile. However, the prognosis of patients with two or three VD is not associated with higher rate of MACE (or cardiac clinical outcomes) at 1-year compared to patients with single-VD.