ABSTRACT: Surgical myocardial revascularization (CABG) in patients with unprotected left main coronary artery disease (ULMCA) is a Class I recommendation in the AHA/ACC guidelines, however it is associated with increased perioperative risk in non-ST elevation acute coronary syndromes (NSTE-ACS). The aim of this study was to compare early and late results after percutaneous coronary intervention (PCI) and CABG in this cohort of patients.
Methods. A multicenter prospective registry included 138 patients with patent but severely narrowed (> 50%) ULMCA disease and NSTE-ACS diagnosed between January 2005 and April 2007. After emergent coronary angiography, 63 patients underwent PCI, whiles 75 were assigned for CABG.
Results. Groups were comparable with regard to sex, age and prevalence of diabetes mellitus (DM). They had similar left ventricular ejection fraction, SYNTAX Score and incidence of distal LM stenosis. However, PCI patients were at higher surgical risk (Euroscore 8.7 ± 3.7 vs. 7.4 ± 3.0; p = 0.02) and myocardial infarction incidence (28% vs. 14%; p = 0.07). The 30-day mortality was 1.5% after PCI vs. 12% after CABG (p = 0.043) and major adverse cardiovascular and cerebrovascular events (MACCE) were 3.2% vs. 14.7%, respectively (p = 0.04). After 12 months, there were 4 deaths in the PCI group and 12 deaths in the CABG group (6.3% vs. 16%; p = 0.14). There was no difference in MACCE (9.5% vs. 9.3%; p = ns). Kaplan-Meier analysis revealed a trend toward better survival after PCI (p = 0.07). Revascularization with CABG and a Euroscore > 5 were the independent risk factors influencing early survival, while a Euroscore > 6 was the independent predictor of late mortality.
Conclusions. PCI is a reasonable alternative to CABG in patients with NSTE-ACS and ULMCA stenosis.
J INVASIVE CARDIOL 2009;21:564–569
Key words: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), unprotected left main coronary artery disease, non-ST elevated acute coronary syndrome
The AHA/ACC guidelines state that surgical myocardial revascularization (CABG) is the standard therapy for patients with unprotected left main coronary artery disease (ULMCA). Meanwhile, the use of bare-metal stents (BMS) in comparison to balloon angioplasty has lowered the incidence of abrupt vessel closure, while drug-eluting stents (DES) have significantly lowered the risk of restenosis.1–3 As a result, after years of procedural improvements, left main stenting has been proven to be safe and to offer good late outcomes.
In comparison with surgical myocardial revascularization (CABG), recent studies have shown that PCI is associated with a lower rate of periprocedural adverse events and similar long-term event-free survival in patients with left main disease.4,5 Our latest nonrandomized registry and randomized study comparing LMCA stenting with CABG confirmed these findings and demonstrated that ejection fraction significantly improved after 1-year follow up only in the PCI group.6,7
An additional risk factor for ULMCA patients can be related to coexisting non-ST-elevation acute coronary syndromes (NSTE-ACS). For these patients, an invasive strategy is the treatment of choice.8–10 It should be stressed, however, that unstable angina and non-ST-elevation myocardial infarction (NSTEMI) substantially increase the risk of CABG. In fact, there are limited data on the outcome of ULMCA stenting or CABG in NSTE-ACS patients. Thus, the purpose of this study is to present and compare early and late outcomes after percutaneous and surgical revascularization in patients with ULMCA disease and NSTE-ACS.
Methods
This is a prospective, multicenter registry comparing acute and 1-year outcomes after PCI and CABG in patients with ULMCA disease and NSTE-ACS. Between January 2005 and April 2007, we screened 156 consecutive patients with acute coronary syndrome (ACS) and LMCA disease who were diagnosed and treated at three centers. From this group, 138 patients with NSTE-ACS and severely narrowed, but patent, LMCAs (> 50% and Percutaneous revascularization. In the majority of cases, direct stenting was the preferred technique (n = 43), except in cases of critical and calcified narrowings, which were predilated with a small balloon (2.0–2.5 mm). For distal left main stenosis, stenting across the bifurcation toward the LAD was performed first, followed by provisional stenting of the Cx artery with T-stenting or the “culotte” technique, according to the by the operator’s discretion. Postdilatation with “kissing-balloon” angioplasty was always used to complete the distal left main stenting procedure. DES were used for the LMCA with a reference diameter 50% of viable myocardium coexisting with significantly depressed left ventricular function (LVEF Surgical revascularization. Operations were performed using standard anesthetic techniques. All operations were performed via a median sternotomy, with standard cardiopulmonary bypass and moderate systemic hypothermia. None of the patients underwent off-pump surgery. A left internal mammary artery graft was used in 93% of CABG patients, and radial artery grafting was performed in 1 patient.
Antiplatelet regimen. Acetylsalicylic acid (ASA) (300 mg initial dose followed by 150 mg daily), together with clopidogrel (300–600 mg initial dose and 75 mg daily after completion of the procedure), were started immediately before PCI. Patients undergoing surgical revascularization were pretreated with ASA. Dual-antiplatelet therapy was advised for a 1-year period after both procedures.
Follow up. The 12-month follow-up data were collected by telephone through conversations with the patients or their relatives. Information on any adverse event (including cardiac and non-cardiac death, MI, stroke or repeat revascularization) were recorded and analyzed by the clinical events committee. Follow-up records were confirmed with the National Health System Registry and the Central Registry of Citizens. None of our patients were lost to follow up.
Study endpoint. The primary endpoint was the 30-day incidence of major adverse cardiovascular and cerebrovascular events (MACCE), which included death, MI, stroke, in-stent thrombosis and repeat revascularization.
The secondary endpoints were the incidence of MACCE during the first year after the index procedure, long-term survival, MACCE-free long-term survival and analysis of independent risk factors influencing survival.
Statistical analysis. Parametric data were expressed as the mean and standard error, whereas nonparametric data were expressed as an absolute number and percentage. The parametric variables between groups were compared using unpaired Student’s t-tests. Nonparametric variables were compared using the chi-square and/or Fisher’s exact tests. Survival curves were drawn using Kaplan-Meier analysis. A Gehan-Wilcoxon test was used for comparison of the survival curves between the treatment arms. The risk factors influencing early- and long-term survival were indicated by univariate analysis of risk factors with odds-ratio stratification. The Cox proportional hazards model was used for multivariate logistic analysis of independent risk factors.
Safety issues. PCI procedures were carried out by experienced interventional cardiology teams in high-volume centers (> 1,000 PCIs per year at 1 center, with 300 interventions per operator) with cardiac surgery backup on site or within 60 minutes of emergency transportation. All interventionists underwent special training in LMCA stenting based on the LE MANS protocol. Surgery was performed by experienced cardiac surgery teams (performing 2,000–3,000 CABGs per year, with a mortality rate of 2–3%).
Results
Early outcomes. The two treatment groups were comparable with regard to basic characteristics (Table 1). However, patients undergoing PCI had a higher surgical risk according to their Euroscore (8.7 ± 3.7 vs. 7.4 ± 2.98;
p = 0.023), a trend toward higher rates of MI (28% vs. 14%;
p = 0.072) and prior MI (46% vs. 32%;
p = 0.06). Angiographic data did not reveal any differences between the two groups concerning the extent of coronary artery disease according to the SYNTAX Score (31.7 ± 12.8 vs. 32.5 ± 12.5;
p = 0.7). There was a trend toward a higher percent diameter stenosis (%DS) in the PCI group (80.3 % ± 16.8 vs. 75.6% ± 14.9;
p = 0.086) and a trend toward a higher number of diseased vessels in the CABG group (2.1 ± 0.9 vs. 2.39 ± 0.9;
p = 0.062).
Angiographic success was achieved in 95% of the cases following PCI. Clinical success was recorded in 93% of patients after PCI and in 86% after CABG (
p = ns). Within 30 days from the index procedure, there was 1 death (1.5%) in the PCI group and 9 deaths (12%) in the CABG group (
p = 0.043) (Figure 2). PCI was associated with a lower risk of MACCE (3.2% vs. 14.7%; p = 0.04) (Figure 3) and shorter hospitalization (6 ± 5 vs. 18 ± 11 days;
p = 0.00001). Total revascularization was achieved in 57% of the cases in the angioplasty group and in 97% of the cases in the surgical group (
p = 0.0001). Additionally, 10% of the patients who underwent angioplasty achieved complete revascularization after the second or third procedure performed within 3 months of the first procedure.
Univariate analysis with odds ratio (OR) stratification (Figure 7A) revealed that CABG (OR = 8.1; 95%, confidence interval [CI] = 1.01–66.5), diabetes mellitus (OR = 3.98; 95% CI = 1.1–14.9), age > 65 years (OR = 10.2; 95% CI = 1.3–82.9), Euroscore > 5 (OR = 19.5 1.1–338) and Killip 4 Class (OR = 31; 95% CI 2.6–388) were the risk factors that increased 30-day mortality, while PCI was the single factor that decreased the mortality rate (OR 0.12; CI 0.1–0.9).
Multivariate analysis showed that a Euroscore > 5 and CABG were the independent risk factors that increased 30-day mortality.
Mid-term and late outcomes. A control coronary angiogram after 6–12 months was performed in 35 (55.5%) of patients in the PCI group. Within this cohort, restenosis in the LMCA occurred in 4 cases (11.4%).
During the first year, in total there were 4 deaths (6.3%) in the PCI group and 12 (16%) in the CABG group (
p = 0.173), including 3 deaths in both groups between 1 month up to 12 months (Figure 2).
There were no significant differences between the PCI and CABG groups in the rate of MACCE (9.5% vs. 9.3%;
p = ns), MI (9.5% vs. 5.3%;
p = ns), stroke (0% vs. 4%;
p = ns) or repeat revascularization (7.9% vs. 4.0%;
p = ns) (Figure 3).
Long-term survival (mean follow up 23.7 months) was 86.5% after PCI and 83% after CABG (
p = 0.07), as seen on the Kaplan-Meier curve in Figure 4. A trend toward better survival after PCI was primarily due to the early (30-day) high mortality rate in the CABG group. Furthermore, there were no significant differences in long-term MACCE-free survival between those groups (Figure 5).
In the subgroup of patients who presented with a SYNTAX score p = 0.006), age > 65 years (OR: 3.4; 95% CI: 1.04–11.2;
p = 0.027) and Euroscore > 6 (OR: 5.5; 95% CI: 1.2–25.1;
pM = 0.05) on admission had an impact on survival in these patients. According to multivariate analysis, a Euroscore > 6 on admission was the independent risk factor determining survival over the entire observation period.
Discussion
This is the first study presenting early and long-term results in patients after LMCA stenting in patients with unprotected LMCA disease and non-ST-ACS. Here we show very promising results after LMCA stenting in this high-risk population.
PCI vs. CABG in stable/unstable angina. Multiple studies have shown that the risk of CABG in patients with ACS and multivessel coronary artery disease is higher than in stable angina patients.
11 The ERACI study proved that PCI with stent implantation in a population consisting mainly of ACS patients (90%) is associated with better survival and freedom from MI than after conventional surgery.
12,13 In contrast, no significant differences in early or late mortality rates were observed in studies where the majority of enrolled patients had stable angina (ARTS – > 70%).
11,14 In the SOS trial (80% of patients with stable angina), 1-year mortality was higher after PCI,
11 while 6-year follow up revealed better survival after CABG only in stable angina patients.
15 In both of these studies, the high incidence of target vessel revascularization (TVR) remained a major limitation of PCI. It was improved by application of DES stents in the ARTS II trial, with no difference in survival and MACE-free survival between patients with stable and unstable angina after PCI.
16PCI vs. CABG for ULMCA. Previous registries reported a high incidence of perioperative injury and MI in patients with LMCA disease undergoing CABG,
17 whereas left main stenting has been associated with a low risk of in-hospital death and MI.
1–3
Recently published registries and nonrandomized studies suggest that treatment of ULMCA disease with DES is feasible, resulting in a high procedural success rate and a significant reduction in MACE and restenosis
1–3 Chieffo et al reported a significantly lower risk of 6-month MACE if DES were used for ULMCA stenting (20% vs. 35.9% for DES and BMS, respectively).
2 These findings are consistent with the RESEARCH and T-SEARCH registries, which showed lower mid-term MACE (24% vs. 45%;
p = 0.01) and TVR (6% vs. 23%;
p = 0.004) after DES implantation. Our study presents similar results regarding TVR (4.8% in PCI group). Recently, Colombo’s group reported a single-center retrospective study comparing PCI with DES vs. CABG for ULMCA that showed no difference in the degree of protection against death, stroke, MI and revascularization between the two treatment groups.
4
Our LE MANS randomized study, published recently, showed a significantly lower risk of 30-day serious adverse events and a trend toward better survival after PCI. Moreover, only in the PCI group did LVEF improve significantly after 12 months.
7
In the currently presented new cohort of ACS patients, long-term outcomes were comparable in both groups with respect to the overall MACCE rate, however, there was a trend toward better survival after PCI. This finding corresponds well with the results of Seung et al in their latest MAIN-COMPARE study.
5 Similarly, the SYNTAX trial showed comparable 1-year MACCE risk between PCI and CABG in the LMCA subset,
18 and in the subgroup of SYNTAX scores between 27–32. Our study consisted mainly of such patients (average SYNTAX Score of 31.2).
PCI vs. CABG in high-risk patients. The AWESOME study showed that PCI is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.
19 With the onset of new techniques and possibilities, our registry presents more favorable results after PCI in NSTE-ACS patients with unprotected left main disease (1.6% vs. 12% of early MACCE;
p = 0.04).
There are no published reports on early mortality after CABG in patients with ULMCA and NSTE-ACS. The only available data showed an 8–33% early mortality rate after CABG in patients with ACS but without severe stenosis of the LMCA.
20,21 The early surgical morality rate (12%) observed in our study was consistent with the predicted preoperative risk calculated from the additive and logistic Euroscores,
22 which in the CABG group were 7.4 and 11.72%, respectively.
Our study is the first to include patients with the combined high-risk features of NSTE-ACS and ULMCA disease. The results are consistent with prior reports in the literature regarding CABG and PCI for ULMCA disease and reports of these revascularization techniques in NSTE-ACS.
Study limitations. The primary limitations of our study are the relatively small number of enrolled patients and the non-randomized nature of the comparison. This is related to the fact that surgical revascularization is presently considered the treatment of choice for patients with severe narrowing of the ULMCA.
23
On the other hand, PCI patients, despite higher Euroscores and similar SYNTAX scores, had lower mortality and total MACE rates. This observation highlights the usefulness of PCI in this high-risk population. Based on our findings, we recommend that a large randomized study with similar inclusion criteria be conducted.
Conclusions
This study demonstrated that left main stenting offered significantly better acute results in NSTE-ACS patients compared to CABG, despite the high-risk profile in the PCI group. After 1 year, the difference in mortality was maintained.
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