There is a lack of knowledge on the interaction between age and left main coronary artery revascularization. The aim of this study was to investigate the comparative effectiveness of percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease aged <75 versus ≥75 years. Of a total of 894 patients included, 692 (77.4%) were aged <75 years and 202 (23.6%) ≥75 years. PCI was found to be significantly different from CABG with respect to the composite of major adverse cardiac events at 1-year follow-up in patients aged <75 years (15.5% vs 8.5%, p = 0.01) but not in those aged ≥75 years (16.4% vs 13.9%, p = 0.65). This finding was consistent after statistical adjustment for baseline confounders in the 2 groups (adjusted hazard ratio [AHR] 2.2, 95% confidence interval 1.2 to 4.1, p = 0.016 in younger patients; AHR 0.9, 95% confidence interval 0.3 to 3.0, p = 0.88 in older patients). In the 2 groups, PCI and CABG showed similar adjusted risks for all-cause death, cardiac death, and myocardial infarction. Target lesion revascularization occurred more frequently in patients aged <75 years treated with PCI compared to CABG (AHR 5.1, 95% confidence interval 1.9 to 13.6, p = 0.001) but not in those aged ≥75 years. A significant interaction between age and treatment with regard to major adverse cardiac events was identified (adjusted p for interaction = 0.034). In conclusion, compared to younger patients, elderly patients with left main disease are likely to derive the maximal gain from a less invasive procedure such as PCI.
Coronary artery bypass grafting (CABG) is the standard of care in patients with unprotected left main (LM) coronary artery disease. In a recent meta-analysis of randomized clinical trials, percutaneous coronary intervention (PCI) of the LM coronary artery was found to be associated with more revascularization at 1 year compared to CABG but fewer strokes and similar rates of death and myocardial infarction. Given these results, PCI might be an attractive option for elderly patients, who represent a fast growing segment of the population in Western countries. Elderly subjects, in fact, are typically affected by co-morbidities and extensive coronary artery disease, features that put them at higher risk for adverse events after surgical procedures. Aged patients, however, are generally not included or are typically underrepresented in studies comparing the effectiveness of PCI versus CABG in LM revascularization. As a consequence, there is a comparably low level of evidence to take therapeutic decisions in this high-risk segment of the population. In this analysis, we aimed to investigate the comparative effectiveness of PCI with drug-eluting stents (DES) and CABG in patients aged <75 and ≥75 years old who underwent LM revascularization.
Methods
The Appraise a Customized Strategy for Left Main Revascularization (CUSTOMIZE) registry includes data from 2 centers that performed PCI with DES or CABG in consecutive patients with unprotected LM coronary artery disease from March 2002 to March 2009. This subanalysis focused on 2 subgroups stratified by age at enrollment (<75 or ≥75 years) to address the impact of treatment by age interaction in LM disease. The local ethics committee at each center approved the use of clinical data for this analysis, and all patients provided written informed consent.
Details of procedural and postprocedural practice in patients enrolled in the CUSTOMIZE registry were previously reported. Briefly, the use of predilatation, intra-aortic balloon pump, or intravascular ultrasound and the choice of stents in patients who underwent PCI were at each operator’s discretion. Lesions located at the ostium or shaft of the LM coronary artery were usually treated with single stents. For bifurcation lesions, different stenting strategies were used, including provisional stenting or mini-crush in most patients. Antiplatelet therapy and periprocedural anticoagulation followed standard regimens. After the procedure, PCI patients were prescribed clopidogrel for ≥6 months. Lifelong aspirin was prescribed. Surgical revascularization was performed using standard bypass techniques. Mammary artery conduits were used whenever possible. For those patients receiving aspirin and clopidogrel, if possible, surgery was delayed for 5 days. CABG surgery was performed either “on pump” or “off pump”; in on-pump surgeries, the type of cardioplegia was left to surgical judgment. Postprocedural medication was chosen according to local clinical practice. All patients received aspirin indefinitely.
The primary end point was the incidence of major adverse cardiac events (MACEs) at 1-year follow-up. MACEs were defined as the composite of all-cause death, myocardial infarction, or target lesion revascularization (TLR). Secondary end points were the components of the primary end point (death, myocardial infarction, and TLR) and cardiac death. Myocardial infarction was defined as any typical increase and decrease of biochemical markers of myocardial necrosis with ≥1 of the following: cardiac symptoms, development of Q waves on electrocardiography, or electrocardiographic changes indicative of ischemia. TLR was defined as any repeat revascularization in the target segment. All outcomes of interest were confirmed by collecting source documentation at each center and were centrally adjudicated by an independent, blinded end points committee.
Clinical follow-up data on medical therapy and clinical status were prospectively collected through scheduled outpatient clinic evaluations. Additional information, if necessary, was derived from referring cardiologists, general practitioners, and patients themselves. All revascularization (surgical or percutaneous) and rehospitalization data were prospectively gathered during follow-up through the centralized system of the participating centers or direct contact with the hospitals to which patients were admitted or referred. Angiographic follow-up was recommended at 6 to 9 months from the index procedure in all patients who had undergone PCI; it was carried out earlier if clinically indicated. For CABG-treated patients, angiographic follow-up was suggested only in the occurrence of signs and symptoms of ischemia during follow-up.
Continuous variables are presented as mean ± SD or as median (interquartile range) and were compared using Student’s unpaired t tests or Mann-Whitney rank-sum tests, on the basis of appropriate testing for a normal distribution. Categorical variables are presented as counts and percentages and were compared using chi-square tests when appropriate (expected frequency >5); otherwise, the Fisher’s exact test was used. The Kaplan-Meier method was used to estimate the incidences of clinical end points in PCI and CABG patients and differences between groups were analyzed using the log-rank test. To reduce the effect of selection bias and potential confounding in this observational study, the outcome parameters were adjusted by means of a Cox multivariate proportional-hazard regression model for observed differences with respect to variables with p values <0.01 in the univariate analysis, which were previous PCI, ST-segment elevation myocardial infarction at presentation, left ventricular ejection fraction, European System for Cardiac Operative Risk Evaluation score, SYNTAX Score, distal LM coronary artery disease, LM coronary artery stenosis plus concomitant 3-vessel disease, right coronary artery disease, and complete revascularization. The assumption of the proportional hazard was verified by a visual examination of the log (minus log) curves, and the linearity assumption was assessed by plotting the Martingale residuals against continuous covariates. Results are presented as hazard ratios and 95% confidence intervals. The interaction effect of age with revascularization strategy was determined using a Cox proportional-hazard regression analysis with age, treatment, their multiplicative interaction term, and adjusting covariates entered in the model. Statistical analyses were performed using SPSS version 17.0 (SPSS, Inc., Chicago, Illinois).
Results
Of a total of 894 patients, 692 (77.4%) were aged <75 years and 202 (22.6%) ≥75 years. Their baseline characteristics are listed in Table 1 .
| Variable | <75 Years Old | ≥75 Years Old | ||||
|---|---|---|---|---|---|---|
| PCI (n = 241) | CABG (n = 451) | p Value | PCI (n = 84) | CABG (n = 118) | p Value | |
| Age (years) | 62.0 ± 8.2 | 62.5 ± 8.6 | 0.41 | 78.8 ± 2.9 | 78.1 ± 2.9 | 0.14 |
| Men | 83.0% | 82.7% | 1.00 | 67.9% | 66.9% | 1.00 |
| Systemic hypertension | 65.6% | 71.2% | 0.15 | 79.8% | 80.5% | 1.00 |
| Hypercholesterolemia ⁎ | 59.3% | 54.1% | 0.21 | 56.0% | 56.8% | 1.00 |
| Smoking | 45.2% | 52.5% | 0.08 | 34.5% | 29.7% | 0.56 |
| Diabetes mellitus | 34.4% | 41.2% | 0.10 | 29.8% | 39.0% | 0.23 |
| Creatinine >2 mg/dl | 2.1% | 0.9% | 0.34 | 8.3% | 3.4% | 0.23 |
| Previous myocardial infarction | 36.1% | 31% | 0.20 | 33.3% | 31.4% | 0.89 |
| Peripheral artery disease | 14.9% | 12.9% | 0.52 | 27.4% | 17.8% | 0.15 |
| Chronic obstructive pulmonary disease | 9.1% | 5.1% | 0.06 | 16.7% | 7.6% | 0.07 |
| Previous PCI | 31.1% | 13.5% | <0.001 | 20.2% | 6.8% | 0.008 |
| Clinical presentation | ||||||
| Unstable angina pectoris/non–ST-segment elevation myocardial infarction | 53.9% | 57.4% | 0.42 | 63.1% | 57.6% | 0.52 |
| Acute myocardial infarction | 7.9% | 0.4% | <0.001 | 6.0% | 0.8% | 0.09 |
| Left ventricular ejection fraction (%) | 50.4 ± 9.8 | 52.0 ± 8.6 | 0.032 | 45.0 ± 11.5 | 49.9 ± 9.4 | 0.001 |
| <30% | 3.7% | 2.0% | 0.26 | 15.5% | 3.4% | 0.005 |
| European System for Cardiac Operative Risk Evaluation score | 3.9 ± 2.2 | 4.0 ± 2.5 | 0.53 | 8.5 ± 2.4 | 7.3 ± 2.2 | <0.001 |
| Lesion location | ||||||
| Ostium | 31.5% | 15.8% | <0.001 | 44.0% | 14.0% | <0.001 |
| Shaft | 15.4% | 5.0% | <0.001 | 11.9% | 9.3% | 0.74 |
| Distal | 53.1% | 79.2% | <0.001 | 44.1% | 76.7% | <0.001 |
| Extent of coronary artery disease | ||||||
| Isolated LM disease | 9.8% | 5.8% | 0.08 | 7.5% | 1.7% | 0.12 |
| LM plus 1-vessel disease | 35.1% | 12.8% | <0.001 | 37.3% | 16.7% | 0.003 |
| LM plus 2-vessel disease | 33.8% | 31.2% | 0.52 | 26.9% | 31.3% | 0.64 |
| LM plus 3-vessel disease | 21.3% | 50.2% | <0.001 | 28.3% | 50.3% | 0.006 |
| Right coronary artery disease | 44.0% | 70.8% | <0.001 | 50.7% | 74.8% | 0.002 |
| SYNTAX Score | 24.9 ± 11.1 | 32.2 ± 12.6 | <0.001 | 26.3 ± 10.2 | 36.4 ± 12.3 | <0.001 |
| Complete revascularization † | 49.3% | 77.4% | <0.001 | 36.8% | 66.0% | <0.001 |
⁎ Defined as serum cholesterol >200 mg/dl.
† Defined as the successful treatment of all vessels ≥1.5 mm in diameter with stenoses ≥50%, as identified by the interventional cardiologist and cardiac surgeon after coronary angiography and estimated after the procedure by the investigators.
Among younger patients, PCI and CABG were performed in 35% and 65% of patients, respectively. Patients who underwent PCI were more likely to present with ST-segment elevation myocardial infarction and history of revascularization. Patients who underwent CABG had higher SYNTAX Scores (32 ± 13 vs 25 ± 11, p <0.001) and were more likely to present with distal LM coronary artery disease and concomitant 3-vessel involvement compared to those who underwent PCI. Not surprisingly, CABG achieved a higher rate of complete revascularization compared to PCI (77% vs 49%, p <0.001). The rate of follow-up angiography was higher in patients who underwent PCI compared to CABG (74% vs 11%, p <0.001).
In older patients, 41% of patients underwent PCI and 59% of patients underwent CABG. Patients who underwent PCI were more likely to present with worse clinical conditions than those who underwent CABG, as reflected by their higher European System for Cardiac Operative Risk Evaluation scores (9 ± 2 vs 7 ± 2, p <0.001). Once again, older patients who underwent CABG presented with higher SYNTAX Scores (36 ± 12 vs 26 ± 10, p <0.001) and were more likely to present with distal LM coronary artery disease and concomitant 3-vessel involvement compared to those who underwent PCI. The rates of complete revascularization (66% vs 37%, p <0.001) and follow-up angiography (6% vs 49%, p <0.001) with CABG and PCI were numerically lower than in the younger counterpart.
At 1 year, significantly more MACEs were seen with PCI compared to CABG in younger patients (15.5% vs 8.5%, p = 0.01; Table 2 , Figure 1 ). This difference was driven by a higher incidence of TLR in patients who underwent PCI, while no differences were noted in terms of all-cause death, cardiac death, and myocardial infarction. After adjustment for baseline confounders, PCI remained associated with a higher risk for MACEs (adjusted hazard ratio 2.2, 95% confidence interval 1.2 to 4.1, p = 0.016), mostly explained by a higher likelihood of repeat revascularization.
| PCI | CABG | Unadjusted | Adjusted | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | p Value | HR (95% CI) | p Value | |||
| Age <75 years | ||||||
| MACEs | 15.50% | 8.50% | 1.9 (1.2–3.0) | 0.01 | 2.2 (1.2–4.1) | 0.016 |
| Death | 5.40% | 5.40% | 0.1 (0.5–2.0) | 0.92 | 1.1 (0.4–2.7) | 0.87 |
| Cardiac death | 3.60% | 4.90% | 0.7 (0.3–1.6) | 0.42 | 0.9 (0.3–2.7) | 0.89 |
| MI | 1.30% | 0.80% | 1.7 (0.3–8.4) | 0.52 | 1.4 (0.2–13.6) | 0.75 |
| TLR | 9.40% | 2.40% | 4.0 (1.8–8.7) | 0.001 | 5.1 (1.9–13.6) | 0.001 |
| Age ≥75 years | ||||||
| MACEs | 16.40% | 13.90% | 1.2 (0.6–2.6) | 0.65 | 0.9 (0.3–3.0) | 0.88 |
| Death | 9.90% | 11.20% | 0.9 (0.3–2.9) | 0.77 | 0.4 (0.1–1.5) | 0.18 |
| Cardiac death | 5.50% | 8.40% | 0.6 (0.2–2.1) | 0.49 | 0.3 (0.1–1.2) | 0.08 |
| MI ⁎ | 1.40% | 2.00% | 0.7 (0.1–8.1) | 0.8 | — | — |
| TLR | 5.80% | 1.10% | 6.0 (0.7–53.6) | 0.11 | 16.9 (0.8–334.3) | 0.06 |
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