In this study we investigated the impact of acute coronary syndromes (ACSs) on clinical outcomes in patients with unprotected left main coronary artery (ULMCA) stenosis treated with drug-eluting stents (DESs). In this multicenter, retrospective, observational study we enrolled 1,101 patients with ULMCA stenosis treated with DESs. Six hundred eleven patients presented with ACS and 490 had stable coronary artery disease. ACS was defined as the presence of unstable angina or non–ST-segment elevation myocardial infarction (MI). During 2-year follow-up, the adjusted hazard ratio of cardiac mortality and MI of patients with ACS versus stable patients was 2.42 (95% confidence interval 1.37 to 4.28, p = 0.002). We observed a stepwise risk increase, namely patients with stable coronary disease had the lowest risk, patients with unstable angina an intermediate risk, and patients with non–ST-segment elevation MI the highest risk. The increased risk of cardiac mortality and MI of patients with ACS was concentrated in the first year after DES implantation. In conclusion, patients with ULMCA stenosis and ACS treated with DESs have an increased risk of cardiac mortality and MI during the first year after the intervention compared to stable patients.
No previous study has addressed the impact of clinical presentations on 2-year clinical outcomes in patients with unprotected left main coronary artery (ULMCA) stenosis treated with drug-eluting stents (DESs). Therefore, we investigated the independent prognostic value of acute coronary syndromes (ACSs) in a large cohort of patients with ULMCA stenosis treated with DESs enrolled in the survey promoted by the Gruppo Italiano Studi Emodinamici (GISE-SICI). Furthermore, we stratified patients with ACS as those with unstable angina and those with non–ST-segment elevation myocardial infarction (NSTEMI) and compared 2-year clinical outcomes.
Methods
Characteristics of the GISE-SICI Survey on ULMCA Stenosis have been already reported in detail. Briefly, it was a multicenter, retrospective, observational study performed in patients with ULMCA stenosis treated with percutaneous coronary intervention (PCI). All interventional high-volume centers performing >800 PCI per year in Italy and affiliated with GISE-SICI were asked to participate in the survey by providing demographic, clinical, procedural, and follow-up data on consecutive patients with ULMCA stenosis treated with PCI from January 2002 to December 2006. We excluded patients with ST-segment elevation acute myocardial infarction (MI) necessitating primary PCI and those in cardiogenic shock. ACS was defined as unstable angina or non–ST-segment elevation MI (NSTEMI). For this analysis we included only patients treated with DESs. Other definitions of the study have been already published in detail. The decision to perform PCI instead of coronary artery bypass grafting reflected the current practice and strategy of each center according to its indications and protocols to treat ULMCA stenosis. Use of the various devices and administration of therapies during the procedure were left to the operator’s discretion. The study was approved by local ethic committees.
The primary objective of the study was to compare the 2-year cumulative risk of cardiac mortality and MI in patients with ACS to those with stable coronary artery disease. Data are presented as mean ± SD or median and range, as appropriate. Continuous data between groups were compared using unpaired Student’s t test or Mann-Whitney rank-sum test, as appropriate. Categorical variables were compared by chi-square statistics or Fisher’s exact test, as appropriate. Survival, survival free from cardiac death, MI-free survival, and target lesion revascularization–free survival were analyzed by the Kaplan-Meier method and differences between groups were analyzed with log-rank test. Independent predictors of 2-year cardiac mortality and MI were analyzed using Cox proportional hazards regression model. Two criteria were considered necessary for a variable to be entered in the model: a plausible association with the risk of cardiac mortality or MI and availability in the database ≥85%. Therefore, the following variables were included in the model: clinical presentation (ACS vs stable patients), age, gender, diabetes, renal dysfunction, multivessel disease and left ventricular ejection fraction.
Given the nonrandomized nature of the study, to minimize any selection bias, a second multivariable analysis was performed using propensity score as a covariate. Propensity score was determined by use of a logistic regression model from which the probability of having an ACS rather than a stable coronary artery disease was calculated for each patient. The following variables were included in the model: age, gender, hypertension, diabetes mellitus, hypercholesterolemia, smoking, renal dysfunction, European System for Cardiac Operative Risk Evaluation, left ventricular ejection fraction, lesion location, multivessel disease, and use of glycoprotein IIb/IIIa inhibitors. Model discrimination was assessed with the c-statistic and model calibration with the Hosmer-Lemeshow statistic. We performed landmark analyses of the composite of cardiac mortality and MI considering 3 periods of interest: from PCI to 30 days, from 31 days to 1 year, and from 1 year to 2 years. We performed Kaplan-Meier analyses and Cox regression analyses adjusted for propensity score. Statistical analyses were performed using SPSS 12.0 for Windows (SPSS, Inc., Chicago, Illinois) and STATA/SE 9.2 for Windows (STATA Corp, LP, College Station, Texas). A p value <0.05 was considered statistically significant.
Results
From January 2002 to December 2006, 1,111 patients with ULMCA stenosis were treated with DESs at 19 high-volume interventional Italian centers associated with the GISE-SICI. Ten patients were excluded because data on clinical presentation were not available, and, therefore, the final study cohort consisted of 1,101 patients. Six hundred eleven patients presented with ACS and 490 had stable coronary artery disease. Clinical characteristics of the 2 groups of patients are listed in Table 1 . Patients with ACS presented a higher clinical risk profile because they were older, had a lower left ventricular ejection fraction, and presented more frequently with co-morbidities. Of patients with ACS, 358 had unstable angina and 178 had NSTEMI (for 75 patients with ACS this information was not available). Clinical characteristics of these 2 groups of patients are presented in Table 2 .
| Variable | ACS | Stable | p Value |
|---|---|---|---|
| (n = 611) | (n = 490) | ||
| Age (years), median (range) | 73 (29–97) | 68 (36–91) | <0.001 |
| Men | 425 (70%) | 392 (80%) | <0.001 |
| Systemic hypertension | 436 (75%) | 294 (61%) | <0.001 |
| Diabetes mellitus | 214 (36%) | 105 (22%) | <0.001 |
| Hypercholesterolemia ⁎ | 361 (62%) | 304 (64%) | 0.67 |
| Smoker | 219 (38%) | 163 (34%) | 0.26 |
| Chronic pulmonary disease | 58 (14%) | 22 (6%) | <0.001 |
| Renal dysfunction | 76 (13%) | 42 (9%) | 0.03 |
| Peripheral vascular disease | 112 (28%) | 61 (16%) | <0.001 |
| EuroSCORE, median (range) | 6 (0–18) | 3 | <0.001 |
| Left ventricular ejection fraction (%), median (range) | 52 (20–80) | 55 (20–80) | <0.001 |
| Lesion location | 0.18 | ||
| Ostium | 134 (22%) | 87 (18%) | |
| Shaft | 63 (10%) | 47 (10%) | |
| Bifurcation | 414 (68%) | 165 (46%) | |
| Bifurcation technique | 0.005 | ||
| 1 stent | 262 (64%) | 190 (54%) | |
| 2 stents | 149 (36%) | 165 (46%) | |
| Multivessel coronary disease | 370 (65%) | 223 (48%) | <0.001 |
| Multivessel treatment | 148 (32%) | 131 (32%) | 0.97 |
| Glycoprotein IIb/IIIa inhibitors | 194 (32%) | 129 (26%) | 0.06 |
| ≥6-month dual antiplatelet therapy | 285 (77%) | 226 (83%) | 0.08 |
| Variable | UAP | NSTEMI | p Value |
|---|---|---|---|
| (n = 358) | (n = 178) | ||
| Age, median (range) | 71 (29–95) | 75 (35–97) | 0.001 |
| Men | 257 (72%) | 117 (66%) | 0.18 |
| Systemic hypertension | 269 (76%) | 131 (74%) | 0.66 |
| Diabetes mellitus | 138 (39%) | 59 (33%) | 0.26 |
| Hypercholesterolemia | 234 (66%) | 111 (66%) | 0.45 |
| Smoke | 138 (39%) | 75 (43%) | 0.48 |
| Chronic pulmonary disease | 34 (12%) | 24 (18%) | 0.14 |
| Renal dysfunction | 37 (11%) | 33 (19%) | 0.02 |
| Peripheral vascular disease | 66 (24%) | 46 (35%) | 0.03 |
| EuroSCORE, median (range) | 6 (1–15) | 7 (0–18) | <0.001 |
| Left ventricular ejection fraction (%), median (range) | 54 (20–80) | 50 (20–75) | 0.06 |
| Lesion location | 0.001 | ||
| Ostium | 84 (23%) | 23 (13%) | |
| Shaft | 44 (12%) | 13 (7%) | |
| Bifurcation | 230 (65%) | 142 (80%) | |
| Bifurcation techniques | 0.09 | ||
| 1 stent | 137 (60%) | 98 (69%) | |
| 2 stents | 91 (40%) | 43 (31%) | |
| Multivessel disease | 229 (65%) | 105 (59%) | 0.25 |
| Multivessel treatment | 61 (29%) | 51 (29%) | 0.98 |
| Glycoprotein IIb/IIIa inhibitors | 101 (28%) | 69 (39%) | 0.02 |
| ≥6-month dual antiplatelet therapy | 149 (78%) | 135 (86%) | 0.06 |
Two-year survivals free from cardiac mortality and MI were 86% in patients with ACS and 96% in stable patients (p <0.00001). In particular, survival, survival free from cardiac mortality, and MI-free survival were 86%, 91%, and 94% in patients with ACS, respectively, and 95%, 97%, and 97% in patients with stable coronary artery disease (for survival, p = 0.00001; for survival free from cardiac mortality, p = 0.00001; for survival free from MI, p = 0.05). In contrast, target lesion revascularization–free survival was similar between the 2 groups (p = 0.35). We then stratified patients with ACS as those with unstable angina and those with NSTEMI and analyzed 2-year clinical outcomes. We observed a stepwise risk increase, with patients with stable coronary artery disease having the lowest risk, patients with unstable angina an intermediate risk, and patients with NSTEMI the highest risk. In particular, cumulative risks of 2-year cardiac mortality and MI were 12% in unstable patients and 19% in patients with NSTEMI (for unstable vs stable patients, p = 0.004; for unstable patients vs those with NSTEMI, p = 0.03; for stable patients vs those with NSTEMI, p = 0.00001). Moreover, survival, survival free from cardiac mortality, and MI-free survival were 88%, 93%, and 94% in patients with unstable angina, respectively, and 82%, 88%, and 93% in patients with NSTEMI ( Figure 1 ). In contrast, target lesion revascularization–free survival was similar among the 3 groups ( Figure 1 ). By Kaplan-Meier landmark analyses, patients with ACS presented an increased risk of cardiac mortality and MI in the first month after DES implantation and in the period from 1 month to 1 year, but not from 1 year to 2 years ( Figure 2 ).
