One-year clinical outcomes of protected and unprotected left main coronary artery stenting
Michael P. Kelleya,
Bruce D. Klugherza,
Seyed M. Hashemia,
Nicolas F. Meneveaub,
Janet M. Johnstonc,
William H. Matthai, Jra,
Vidya S. Bankaa,
Howard C. Herrmanna,
John W. Hirshfeld, Jra,
Stephen E. Kimmela,
Daniel M. Kolanskya,
Phillip A. Horwitza,
Francois Schieleb,
Jean-Pierre L. Bassandb and
Robert L. Wilenskya,*
a University of Pennsylvania Health System, Philadelphia, PA, USA
b Hôpital Jean Minjoz,Besancon, France
c University of Pittsburgh, Pittsburgh, PA, USA
* Corresponding author: Robert L. Wilensky, MD, Associate Professor of Medicine, Hospital of the University of Pennsylvania, 9 Gates, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel.: +1-215-615-3060; fax: +1-215-615-3073
E-mail address: robert.wilensky{at}uphs.upenn.edu
Received 26 November 2002;
revised 5 May 2003;
accepted 28 May 2003
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Abstract
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Aims To evaluate outcomes for left main coronary artery (LMCA) stenting and compare results between protected (left coronary grafted) and unprotected LMCA stenting in the current bare-metal stent era.
Methods We reviewed outcomes among 142 consecutive patients who underwent protected or unprotected LMCA stenting since 1997. All-cause mortality, myocardial infarction (MI), target-lesion revascularization (TLR), and the combined majoradverse clinical event (MACE) rates at one year were computed.
Results Ninety-nine patients (70%) underwent protected and 43 patients (30%) underwent unprotected LMCA stenting. In the unprotected group, 86% were considered poor surgical candidates. Survival at one year was 88% for all patients, TLR 20%, and MACE 32%. At one year, survival was reduced in the unprotected group (72% vs. 95%, P<0.001) and MACE was increased in the unprotected patients (49% vs. 25%, P=0.005).
Conclusions In the current era, stenting for both protected and unprotected LMCA disease is still associated with high long-term mortality and MACE rates. Stenting for unprotected LMCA disease in a high-risk population should only be considered in the absence of other revascularization options. Further studies are needed to evaluate the role of stenting for unprotected LMCA disease.
Key Words: Cardiogenic shock Coronary artery bypasssurgery Coronary artery disease Left main disease Percutaneous coronaryintervention
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1. Introduction
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The presence of a left main coronary artery (LMCA) stenosis identifies an anatomic subset still requiring bypass surgery for revascularization rather than percutaneous coronary intervention (PCI). Since early studies of balloon angioplasty for LMCA disease demonstrated poor acute and long-term survival rates,1,2angioplasty alone has been contraindicated for treatment of left main disease. Recent studies have demonstrated the feasibility of stenting for LMCA disease,35although data remain limited. Accordingly, we studied the one-year clinical follow-up of a recent cohort of consecutive patients receiving a stent for either protected (left coronary grafted) or unprotected left main disease.
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2. Methods
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2.1. Study population
The databases of the University of Pennsylvania Health System (Philadelphia, PA), Hôpital Jean Minjoz (Besancon, France), and Waves 1 and 2 of the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry6were reviewed for patients who underwent successful LMCA stent implantation for a symptomatic stenosis greater than 50% in diameter. Only patients undergoing stent implantation after January 1997 during the time period of routine stenting were included. Left main distal coronary lesions involving the left anterior descending (LAD) or circumflex ostia were routinely treated with additional ostial stenting. Clinical follow-up at one year was obtained via direct patient contact or telephone contact. When necessary, this information was supplemented by the medical or cardiac catheterization records.
2.2. Definitions
Death included both cardiac and non-cardiac causes. Myocardial infarction was defined as prolonged chest pain or shortness of breath accompanied by either characteristic electrocardiographic changes or enzyme elevations requiring hospital admission. Target-lesion revascularization was defined as any repeat PCI or coronary artery bypass grafting (CABG) for a restenotic left main lesion >50% in severity. The major adverse cardiac event (MACE) rate included death, non-fatal myocardial infarction, or target-lesion revascularization during follow-up. As defined in previous studies, patients were considered poor surgical candidates for CABG if they had one or more of the following comorbidities: age >75 years, ejection fraction <35%, cardiogenic shock, unsuitable distal targets for bypass, or other medical comorbidities, such as advanced pulmonary disease, renal failure or malignancy.3,4All patients who underwent unprotected LMCA stenting were evaluated jointly by both cardiologists and cardiac surgeons to assess candidacy for either coronary bypass or percutaneous intervention.
2.3. Quantitative coronary angiographic (QCA) analysis
All angiograms were analyzed using an automated edge detection algorithm (MEDIS, Leiden, the Netherlands). The minimal luminal diameter (MLD), average proximal and distal reference diameters, percent stenosis and lesion length were determined for each pair of orthogonal views and then averaged. Lesions were considered significant if the stenosis was greater than 50% in severity.
2.4. Statistical analysis
Continuous data are presented as mean±SD and were compared using the Student t test. Categorical variables were compared using either Chi-square or Fisher exact tests. A KaplanMeier analysis of survival among the protected and unprotected groups was obtained using the log-rank test. A multivariate analysis of mortality was performed utilizing a propensity model.7All baseline clinical and procedural characteristics found in Tables 1 and 2were included in a univariate analysis of mortality. In addition, the use of aspirin, statins, beta blockers, ACE inhibitors, nitrates, and calcium blockers were determined not to be confounders of mortality by univariable analysis. Only those variables that affected the odds ratio of mortality with a P value <0.10 were included in the initial propensity model with unprotected LMCA stenting as the dependent variable. These included age >65 years, hyperlipidemia, glycoprotein IIb/IIIa inhibitor usage, and concomitant PCI of either an ostial left anterior descending or circumflex lesion. Because there were no patients in the protected LMCA group who presented with cardiogenic shock, we could not adjust for shock in the final propensity analysis. However, we adjusted for cardiogenic shock in a separate analysis by excluding these patients. The Hosmer-Lemeshow test was non-significant (P>0.2), demonstrating goodness-of-fit.8Patients were grouped into tertiles by likelihood of undergoing an unprotected LMCA stent based on the initial model. These tertiles were then included in a stratified analysis of the effect of unprotected LMCA stenting on one-year mortality. Adjusted odds ratios (OR) were determined using the Mantel-Haenszel method, which has been shown to be robust with sparse data.7A P value <0.05 was considered statistically significant and confidence intervals are 95%. All statistical analyses were performed using SPSS, version 10.0 (SPSS Inc., Chicago, IL).
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3. Results
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3.1. Patient Characteristics
In total, 142 total patients underwent stent implantation for LMCA disease, of which 99 patients had protected (70%) and 43 had unprotected (30%) left main stenoses. Left main stenting accounted for 0.86% of coronary interventions at all participating institutions (protected 0.54%, unprotected 0.32%). Baseline clinical characteristics are presented in Table 1. The mean age was 68 years (range 4591), and the majority of patients were male. Patients in the unprotected group were older, more likely to present with an acute myocardial infarction or cardiogenic shock (19% vs. 0%, P<0.0001), and 86% were poor candidates for CABG. The reasons patients were deemed poor surgical candidates include advanced age (19%), poor left ventricular function (13%), unsuitable distal targets for bypass (8%), cardiogenic shock (22%), and other medical comorbidities, such as renal insufficiency, severe pulmonary disease or malignancy (38%). There were six patients in the unprotected group who were otherwise good surgical candidates, five of these patients refused surgery and one patient underwent an emergent intervention in the setting of an acute myocardial infarction not associated with cardiogenic shock.
The baseline angiographic characteristics are shown in Table 2. The majority of lesions were distal in location. Left main location did not influence outcomes. By QCA analysis, the mean reference vessel diameter for the entire group was 3.63±0.72mm prior to the procedure, and the MLD was 1.38±0.64mm representing a mean diameter stenosis of 63%. After intervention, the MLD was increased to 3.15±0.69mm (14% residual stenosis). A decrease in the periprocedure reference diameter may have reflected vascular tone since no increased vascular injury was noted immediately following the procedure. There were no significant differences between the protected and unprotected groups by QCA analysis. Adjunctive rotational atherectomy was performed in 53 patients (37%) and glycoprotein IIb/IIIa inhibitors were used in 62 patients (44%); these therapies were utilized less often in the unprotected LMCA group. In the unprotected group, 37% underwent bifurcation stenting of either an ostial LAD or circumflex lesion. Bifurcation stenting did not affect outcomes.
3.2. Follow-up
Clinical follow-up at one year was available for 96% of patients (Table 3). The in-hospital mortality rate was significantly higher for patients undergoing unprotected LMCA stenting compared to protected (9.3% vs 2.1%, P<0.001). At one year, the survival was significantly reduced in the unprotected group (72% vs 95%, P<0.001, Fig. 1). The high peri-procedural mortality in the unprotected LMCA group was likely due to the prevalence of severe left ventricular dysfunction and cardiogenic shock that was associated with three of the four peri-procedural deaths in the unprotected group. For the eight patients presenting with cardiogenic shock, all in the unprotected group, survival was 50% at one year. After excluding these patients, the one-year survival for the unprotected LMCA patients was still significantly worse than the protected group (77% vs 95%, P=0.007). In the unprotected group, the 1-year death rates according to the primary reason for non-surgical revascularization include 0% for age >75, 40% for ejection fraction <35%, 25% for poor distal targets, 50% for cardiogenic shock, and 36% for a severe medical comorbidity (P=ns). There were two patients which underwent unprotected LMCA stenting rather than CABG because of malignancy and both of these patients were alive at one year. The univariate predictors of mortality at one year are presented in Table 4. In multivariable analysis, the presence of an unprotected LMCA remained a significant predictor of mortality (OR 4.9, 1.515.5, P=0.008). When excluding patients with cardiogenic shock, unprotected left main stenting was still a multivariate predictor of mortality (OR 4.1,1.214.2, P=0.03).
Target-lesion revascularization at one year was 20% for all patients, and there were no differences among the protected and unprotected groups (18% vs 23%, P=ns, Table 3). At one year, MACE rates were almost twice as high in the unprotected compared to protected group (49% vs 25%, P=0.005). Fifteen percent of patients in both the protected and unprotected groups underwent PCI of a non-left main stenosis by one year of follow-up. PCI of a non-left main lesion was not predictive of either mortality or MACE.
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4. Discussion
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Despite use of new treatments for percutaneous intervention, including stent implantation, adjunctive atheroablative techniques and glycoprotein IIb/IIIa inhibitors, the one-year survival rate for stenting of left main disease was only 88% in this study. Patients who underwent unprotected LMCA stenting represented a high-risk subgroup, with the majority of the patients in the group classified as poor surgical candidates based on advanced age or other comorbidities. Inclusion of these higher risk patients for unprotected LMCA stenting introducesselection bias, which may help to explain the high one-year mortality of 28% found in the unprotected group when compared to the 5% rate in the protected group. However, the one-year mortality for the protected patients in the current study, although similar to previous studies,9is still higher than reported rates for non-LMCA procedures,6,10which may reflect an increased mortality in patients with well-established coronary artery disease who have previously undergone CABG. Similarly, the one-year MACE rate of 25% for stenting of protected LMCA disease found in the present study, comparable to a previous report by Lopez et al.,9is higher than the one-year event rates of PCI for other coronary lesions.10The majority of the patients in this study had a significant stenosis in at least one non-left main vessel, suggesting a heavy atherosclerotic burden which may, in part, explain the poor mortality and MACE rates in addition to the presence of other significant comorbidities.
The Coronary Artery Surgery Study (CASS) demonstrated 1-year and 5-year survival rates of 90% and 85% respectively for surgical revascularization of a left main stenosis, excluding patients having a previous CABG.11Recent studies of outcomes for repeat CABG, encompassing both protected left main disease and other coronary lesions, include a peri-operative mortality of 710%, and 1 and 5-year survival rates of 8689% and 7679% respectively.12,13Repeat bypass surgery is also associated with an 8% risk of stroke, wound complications, or reoperation for bleeding.12Hence, the 2% peri-procedural mortality and 95% one-year survival for protected left main stenting in our study appear comparable to outcomes for a repeat coronary bypass surgery while avoiding potential morbidity associated with a repeat operation.
Recent studies of routine stenting for patients with unprotected LMCA disease have demonstrated differences in procedural results between patients defined as good or poor surgical candidates. The one-year survival for unprotected LMCA stenting involving good surgical candidates is approximately 9598%.35,14For poor surgical candidates, survival at one year has ranged from 7989%, similar to our data.35,14In the ULTIMA registry, which included stented (69%) and non-stented patients, 68% of the 279 total patients were considered poor surgical candidates.15,16The one-year survival in this high-risk subgroup was 66%, similar to our data. As such, the indication for stent implantation of unprotected LMCA disease likely reflects more emergent indications for immediate revascularization, such as acute myocardial infarction, cardiogenic shock or the presence of other serious comorbidities that preclude a more invasive operation. Long-term survival, in turn, is predominantly dictated by these same adverse clinical variables rather than the procedure itself. Hence, current and previous data should be viewed in that context. However, silent restenosis, manifesting itself as death, rather than recurrence of progressive ischemic symptoms, may be responsible, in part, for the increased mortality noted beyond the initial hospitalization (Fig. 1). Evidence of this has been shown in a study by Takagi et al., which demonstrated a 9% mortality rate postulated to be secondary to restenosis in 67 patients undergoing PCI of an unprotected left main lesion.14Tan et al. showed a mortality rate of 2% per month over the initial 6 months after PCI of an unprotected LMCA stenosis.16Given the relatively high death rate during follow-up, current clinical practice is routine angiography 36 months after stent implantation of an unprotected left main stenosis. A drug-eluting stent could potentially improve some of the late mortality associated with restenosis, but should not affect the high mortality associated with the substantial comorbidity of these patients going into the procedure.
This retrospective study has several limitations. Follow-up angiography was clinically driven and performed in only 55% of patients; thus, the actual angiographic restenosis rate could not be determined. Since the majority of the unprotected left main patients were poor surgical candidates, the role of stenting for LMCA disease was not evaluated adequately in a low-risk population.
In the current era, stenting for protected LMCA disease is still associated with increased mortality and MACE rates compared to PCI of other coronary lesions, but offers a possible alternative to a repeat bypass surgery. Prospective studies of these two treatment strategies seem warranted. Stenting for unprotected LMCA disease in a high-risk population is associated with a poor one-year survival and should only be considered in the absence of other revascularization options. Further studies are needed to definitively define the role of stenting for unprotected LMCAdisease.
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