The aim of the study was to assess the impact of multivessel coronary artery disease (MVD) and noninfarct-related artery (non-IRA) revascularization during index percutaneous coronary intervention (PCI) on outcomes of patients with ST-segment elevation myocardial infarction (STEMI). Data on 1,598 of 1,650 patients with complete angiographic data, with ≥1 significantly stenosed epicardial coronary artery, and without previous coronary artery bypass grafting were retrieved from the EUROTRANSFER Registry database. Patients with 1-, 2-, and 3-vessel disease made up 48.5%, 32.0%, and 19.5% of the registry population, respectively. Patients with MVD were less likely to achieve final Thrombolysis In Myocardial Infarction grade 3 flow (1- vs 2- vs 3-vessel disease, 93.6% vs 89.3% vs 87.9%, respectively, p = 0.003) and ST-segment resolution >50% within 60 minutes after PCI (1- vs 2- vs 3-vessel disease, 80.9% vs 77.5% vs 69.3%, respectively, p <0.001). They were also at higher risk of death during 1-year follow-up (1- vs 2- vs 3-vessel disease, 4.9% vs 7.4% vs 13.5%, respectively, p <0.001), and MVD was identified as an independent predictor of 1-year death. In 70 patients (9%) non-IRA PCI was performed during index PCI. These patients were at higher risk of 30-day and 1-year death compared to patients without non-IRA PCI, but this difference in mortality was no longer significant after adjustment for covariates. In conclusion, patients with MVD have decreased epicardial and myocardial reperfusion success and had worse prognosis after primary PCI for STEMI compared to patients with 1-vessel disease. In this large multicenter registry, non-IRA PCI during the index procedure was performed in 9% of patients with MVD and it was associated with increased 1-year mortality.
Concomitant significant stenosis in coronary arteries other than the infarct-related artery (IRA) is observed in 40% to 60% of patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Importantly, the presence of multivessel coronary artery disease (MVD) in a STEMI setting is associated with an adverse prognosis. In addition, optimal treatment of such patients is not definitely established. According to current recommendations non-IRA revascularization during primary PCI is discouraged, especially in hemodynamically stable patients. In contrast, data supporting these recommendations are still rather limited. The present study assessed the impact of MVD and non-IRA revascularization during index PCI on outcomes in an unselected cohort of patients with STEMI based on data from the European Registry on Patients with ST-Elevation MI Transferred for Mechanical Reperfusion with a Special Focus on Upstream Use of Abciximab (EUROTRANSFER) Registry.
Methods
A detailed description of the EUROTRANSFER Registry ( http://ClinicalTrials.gov , number NCT00378391 ) protocol and main results have been previously published. In this registry data concerning 1,650 consecutive, transferred patients with STEMI in 15 STEMI hospital networks from 7 European countries from November 2005 to January 2007 were collected. For the present analysis data of 1,598 patients with complete angiographic data, with ≥1 significantly stenosed epicardial coronary artery, and without previous coronary artery bypass grafting were assessed. Patients were classified at the investigators’ discretion as having 1-, 2-, or 3-vessel disease. Patients with isolated significant left main coronary artery stenosis were classified as having 2-vessel disease. The study protocol and execution complied with the Declaration of Helsinki and was approved by the Jagiellonian University bioethics committee in Krakow, Poland.
The primary end point of the present analysis was 1-year all-cause mortality. In addition, rates of all-cause death, nonfatal reinfarction, urgent revascularization (PCI or coronary artery bypass grafting), puncture site hematoma, intracranial hemorrhage, and major bleeding requiring transfusion at 30 days after PCI were assessed. Events were reported in hierarchical order. Thrombolysis In Myocardial Infarction (TIMI) flow in the IRA before and after PCI, ST-segment resolution after PCI, and rate of angiographic PCI complications (i.e., no-reflow, distal embolization, side branch occlusion, artery perforation) were also assessed at the investigators’ discretion.
Data were analyzed according to established standards of descriptive statistics. Results were presented as numbers of patients (percentages) or medians (interquartile ranges) where applicable. Difference between groups stratified by number of diseased vessels was assessed using chi-square test and Fisher’s exact test for dichotomous variables and Kruskal-Wallis test for continuous variables. Difference in death rates between groups during follow-up was assessed by the Kaplan-Meier method using log-rank test. In addition, multivariate Cox regression analysis was performed to find significant predictors of 1-year death. Forward selection in Cox regression with a probability value for covariates to enter the model was set at the 0.05 level. The following covariates were tested: age, gender, presence of diabetes mellitus, previous MI, previous heart failure symptoms, previous PCI, previous stroke, history of smoking, peripheral arterial disease, chronic renal insufficiency, Killip class IV on admission, MVD (2- or 3-vessel disease), left anterior descending coronary artery as the IRA, patent IRA on baseline angiogram (TIMI grade 2 and 3 flows), and time from symptom onset to diagnosis. Results were presented as hazard ratio and 95% confidence interval. Then differences in clinical outcome between patients with and without non-IRA PCI during index procedure were assessed. Results were adjusted for variables that might influence the non-IRA PCI strategy application by logistic regression analysis. These variables included covariates tested in Cox regression analysis, except MVD presence, and stent implantation and final TIMI grade 3 flow within the IRA. Results were presented as odds ratio with 95% confidence interval. All tests were 2-tailed, and a p value <0.05 was considered statistically significant. All statistical analysis was performed using SPSS 15.0 (SPSS, Inc., Chicago, Illinois).
Results
Data on 1,598 patients were retrieved from the EUROTRANSFER Registry database. Patients with 1-, 2-, and 3-vessel disease made up 48.5%, 32.0%, and 19.5% of the registry population, respectively. As presented in Table 1 , patients with MVD were older, with a higher prevalence of diabetes mellitus, previous MI, previous heart failure symptoms, previous PCI, and presenting in a higher Killip class on admission than were patients with 1-vessel disease. There was no difference in initial pharmacologic treatment before hospital admission for PCI between groups ( Table 1 ).
| Variable | Number of Coronary Arteries With Significant Narrowing | p Value | ||
|---|---|---|---|---|
| 1 (n = 776) | 2 (n = 511) | 3 (n = 311) | ||
| Age (years) | 61 (52–71) | 66 (57–76) | 70 (60–77) | <0.001 |
| Age ≥65 years | 323 (41.6%) | 282 (55.2%) | 200 (64.3%) | <0.001 |
| Men | 560 (72.2%) | 369 (72.2%) | 224 (72.0%) | 0.99 |
| Body mass index (kg/m 2 ) | 26.6 (24.1–29.4) | 26.7 (24.2–29.3) | 26.6 (24.1–29.7) | 0.96 |
| Diabetes mellitus | 87 (11.2%) | 88 (17.2%) | 80 (25.7%) | <0.001 |
| Insulin | 31 (4.0%) | 28 (5.5%) | 24 (7.7%) | 0.042 |
| Previous myocardial infarction | 60 (7.7%) | 70 (13.7%) | 60 (19.3%) | <0.001 |
| Previous heart failure symptoms | 4 (0.5%) | 9 (1.8%) | 6 (1.9%) | 0.036 |
| Previous percutaneous coronary intervention | 49 (6.3%) | 34 (6.7%) | 33 (10.6%) | 0.039 |
| Previous stroke | 23 (3.0%) | 17 (3.3%) | 16 (5.1%) | 0.20 |
| Current smoker | 319 (41.1%) | 183 (35.8%) | 83 (26.7%) | <0.001 |
| Peripheral arterial disease | 19 (2.4%) | 16 (3.1%) | 15 (4.8%) | 0.12 |
| Chronic renal failure | 12 (1.5%) | 12 (2.3%) | 12 (3.9%) | 0.065 |
| Time from symptom onset to diagnosis (minutes) | 95 (55–202) | 110 (60–207) | 130 (60–240) | 0.065 |
| Aspirin before catheter laboratory | 734 (94.6%) | 478 (93.5%) | 295 (94.9%) | 0.65 |
| Clopidogrel before catheter laboratory | 257 (33.1%) | 172 (33.7%) | 89 (28.6%) | 0.27 |
| Unfractionated heparin before catheter laboratory | 515 (66.4%) | 353 (69.1%) | 222 (71.4%) | 0.24 |
| Abciximab before catheter laboratory | 361 (46.5%) | 217 (42.5%) | 135 (43.4%) | 0.32 |
| Thrombolysis before catheter laboratory | 39 (5.0%) | 31 (6.1%) | 11 (3.5%) | 0.28 |
| Heart rate on admission (beat/min) | 77 (66–88) | 79 (69–90) | 77 (66–90) | 0.37 |
| Systolic blood pressure on admission (mm Hg) | 130 (120–150) | 136 (120–155) | 132 (112–150) | 0.067 |
| Diastolic blood pressure on admission (mm Hg) | 80 (70–90) | 80 (70–90) | 80 (67–88) | 0.003 |
| Killip class on admission | ||||
| I | 666 (85.8%) | 411 (80.5%) | 239 (76.8%) | <0.001 |
| II | 86 (11.1%) | 68 (13.3%) | 41 (13.2%) | |
| III | 10 (1.3%) | 19 (3.7%) | 8 (2.6%) | |
| IV | 14 (1.8%) | 13 (2.5%) | 23 (7.4%) | |
Data concerning interventional treatment are presented in Table 2 . The left anterior descending artery was identified as the IRA less frequently in patients with MVD. Presence of 3-vessel disease was associated with greater usage of intra-aortic balloon pumping. A total of 1,515 patients (94.8% of study population) underwent immediate PCI. Patients with MVD were less likely to receive stents and to achieve TIMI grade 3 flow after PCI ( Table 2 ). Similarly, ST-segment resolution >50% after PCI was less frequently observed in patients with MVD than in patients with 1-vessel disease (1- vs 2- vs 3-vessel disease, 80.9% vs 77.5% vs 69.3%, respectively, p <0.001).
| Variable | Number of Coronary Arteries With Significant Narrowing | p Value | ||
|---|---|---|---|---|
| 1 (n = 776) | 2 (n = 511) | 3 (n = 311) | ||
| Femoral access | 657 (84.7%) | 441 (86.3%) | 279 (89.7%) | 0.095 |
| Left anterior descending coronary artery as infarct-related artery | 383 (49.4%) | 228 (44.6%) | 113 (36.3%) | <0.001 |
| Intra-aortic balloon pumping | 19 (2.4%) | 14 (2.7%) | 26 (8.4%) | <0.001 |
| Immediate percutaneous coronary intervention | 738 (95.1%) | 497 (97.3%) | 280 (90.0%) | <0.001 |
| Number of patients undergoing immediate percutaneous coronary intervention | 738 | 497 | 280 | |
| Time from symptoms onset to PCI (minutes) | 218 (156–345) | 232 (165–355) | 245 (158–389) | 0.056 |
| Thrombolysis In Myocardial Infarction grade 2–3 flow before percutaneous coronary intervention | 206 (27.9%) | 159 (32.0%) | 74 (26.4%) | 0.18 |
| Stent implantation | 702 (95.1%) | 469 (94.4%) | 236 (84.3%) | <0.001 |
| Drug-eluting stent | 186 (25.2%) | 125 (25.2%) | 65 (23.2%) | 0.80 |
| Thrombectomy | 98 (13.3%) | 43 (8.7%) | 32 (11.4%) | 0.044 |
| Noninfarct-related artery percutaneous coronary intervention | 0 (0.0%) | 48 (9.7%) | 22 (7.9%) | <0.001 |
| No reflow | 22 (3.0%) | 20 (4.0%) | 6 (2.1%) | 0.33 |
| Distal embolization | 19 (2.6%) | 6 (1.2%) | 6 (2.1%) | 0.25 |
| Thrombolysis In Myocardial Infarction grade 3 flow after percutaneous coronary intervention | 691 (93.6%) | 444 (89.3%) | 246 (87.9%) | 0.003 |
As presented in Table 3 , patients with MVD were at higher risk of ischemic and bleeding events during 30-day follow-up. In addition, 1-year mortality was higher in patients with MVD than in patients with 1-vessel disease. These differences in mortality were also observed in patients without shock on admission (1- vs 2- vs 3-vessel disease, 30-day mortality 2.2% vs 5.2% vs 9.0%, respectively; 1-year mortality 3.9% vs 7.2% vs 11.5%, respectively, p <0.001 for the 2 comparisons). Kaplan-Meier curves for survival according to number of diseased vessels for the entire population are shown in Figure 1 . In multivariate Cox regression analysis independent predictors of 1-year death were Killip class IV on admission, the left anterior descending coronary artery as the IRA, and MVD ( Table 4 ).
| Variable | Number of Coronary Arteries With Significant Narrowing | p Value | ||
|---|---|---|---|---|
| 1 (n = 776) | 2 (n = 511) | 3 (n = 311) | ||
| 30 days | ||||
| Death | 25 (3.2%) | 28 (5.5%) | 34 (10.9%) | <0.001 |
| Death + nonfatal reinfarction | 37 (4.8%) | 33 (6.5%) | 42 (13.5%) | <0.001 |
| Death + nonfatal reinfarction + urgent revascularization | 37 (4.8%) | 41 (8.0%) | 47 (15.1%) | <0.001 |
| Major bleeding requiring transfusion | 9 (1.2%) | 9 (1.8%) | 7 (2.3%) | 0.34 |
| Intracranial hemorrhage | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | — |
| Puncture site hematoma | 35 (4.5%) | 34 (6.7%) | 27 (8.7%) | 0.025 |
| All bleeding | 41 (5.3%) | 41 (8.0%) | 33 (10.6%) | 0.006 |
| Death + nonfatal reinfarction + major bleeding requiring transfusion | 45 (5.8%) | 38 (7.4%) | 48 (15.4%) | <0.001 |
| 1 year | ||||
| Death | 38 (4.9%) | 38 (7.4%) | 42 (13.5%) | <0.001 |
| Variable | HR | 95% CI | p Value |
|---|---|---|---|
| Killip class IV on admission | 1.95 | 1.18–3.24 | 0.010 |
| Left anterior descending coronary artery as infarct-related artery | 1.92 | 1.30–2.84 | 0.001 |
| 2- or 3- vessel disease (vs 1-vessel disease) | 1.58 | 1.05–2.37 | 0.028 |
In 70 patients (9%) non-IRA PCI was performed during the index procedure. These patients were at higher risk of 30-day and 1-year death compared to patients without non-IRA PCI, but this difference in mortality was no longer significant after adjustment for covariates ( Table 5 ).
| Non-IRA PCI (all patients with multivessel disease) | Non-IRA PCI (patients with 2-vessel disease) | Non-IRA PCI (patients with 3-vessel disease) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No | Yes | p Value | Adjusted OR (95% CI) | Adjusted p Value | No | Yes | p Value | Adjusted OR (95% CI) | Adjusted p Value | No | Yes | p Value | Adjusted OR (95% CI) | Adjusted p Value | |
| (n = 707) | (n = 70) | (n = 449) | (n = 48) | (n = 258) | (n = 22) | ||||||||||
| 30 days | |||||||||||||||
| Death | 42 (5.9%) | 9 (12.9%) | 0.039 | 2.42 (0.96–6.06) | 0.06 | 22 (4.9%) | 3 (6.2%) | 0.72 | 1.18 (0.25–5.46) | 0.84 | 20 (7.8%) | 6 (27.3%) | 0.010 | 4.14 (0.97–17.68) | 0.06 |
| Death + nonfatal reinfarction | 55 (7.8%) | 9 (12.9%) | 0.17 | 1.71 (0.72–4.05) | 0.22 | 27 (6.0%) | 3 (6.2%) | 0.99 | 0.89 (0.21–3.74) | 0.88 | 28 (10.9%) | 6 (27.3%) | 0.036 | 2.65 (0.73–9.71) | 0.14 |
| Death + nonfatal reinfarction + urgent revascularization | 65 (9.2%) | 9 (12.9%) | 0.29 | 1.33 (0.57–3.10) | 0.51 | 33 (7.3%) | 3 (6.2%) | 0.99 | 0.71 (0.17–2.96) | 0.64 | 32 (12.4%) | 6 (27.3%) | 0.10 | 2.12 (0.61–7.35) | 0.24 |
| Major bleeding requiring transfusion | 12 (1.7%) | 2 (2.9%) | 0.36 | 1.81 (0.35–9.27) | 0.48 | 8 (1.8%) | 1 (2.1%) | 0.60 | 1.54 (0.15–16.26) | 0.72 | 4 (1.6%) | 1 (4.5%) | 0.34 | 3.89 (0.23–67.05) | 0.35 |
| Puncture site hematoma | 53 (7.5%) | 4 (5.7%) | 0.65 | 0.58 (0.19–1.75) | 0.33 | 31 (6.9%) | 2 (4.2%) | 0.76 | 0.44 (0.09–2.12) | 0.31 | 22 (8.5%) | 2 (9.1%) | 0.99 | 0.54 (0.08–3.65) | 0.53 |
| All bleeding | 62 (8.8%) | 6 (8.6%) | 0.99 | 0.80 (0.32–2.02) | 0.64 | 37 (8.2%) | 3 (6.2%) | 0.79 | 0.58 (0.16–2.11) | 0.41 | 25 (9.7%) | 3 (13.6%) | 0.47 | 0.89 (0.18–4.29) | 0.88 |
| Death + nonfatal reinfarction + major bleeding requiring transfusion | 62 (8.8%) | 11 (15.7%) | 0.08 | 1.97 (0.90–4.29) | 0.09 | 31 (6.9%) | 4 (8.3%) | 0.76 | 1.02 (0.29–3.63) | 0.97 | 31 (12.0%) | 7 (31.8%) | 0.018 | 2.88 (0.87–9.48) | 0.08 |
| 1 year | |||||||||||||||
| Death | 57 (8.1%) | 11 (15.7%) | 0.043 | 2.04 (0.89–4.66) | 0.09 | 30 (6.7%) | 4 (8.3%) | 0.56 | 1.18 (0.34–4.10) | 0.80 | 27 (10.5%) | 7 (31.8%) | 0.009 | 3.62 (0.90–14.56) | 0.07 |
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