Stenting in Patients With Multivessel Disease
Since 1977, when Gruentzig introduced balloon angioplasty as a less invasive alternative to coronary artery bypass graft surgery, the results have steadily improved. The proportion of complex patients who undergo this procedure has substantially increased, fueled by an unprecedented evolutionary change that has included the discovery of stents and the introduction of potent adjuvant pharmacological agents. Approximately 60% of all patients who undergo coronary artery revascularization via coronary artery bypass graft surgery or percutaneous intervention have multivessel disease that is amenable to treatment by either one of these procedures. Still, the most appropriate type of treatment for these patients is a matter of heated debate. In skilled hands, both techniques are relatively safe and highly effective in reducing angina, and have similar mortality and myocardial infarction rates, albeit fewer additional revascularization procedures in patients who undergo bypass surgery.
In the last decade, several randomized trials have compared percutaneous balloon angioplasty to coronary artery bypass surgery; these studies have shown that bypass surgery may prolong survival in a certain subset of patients. Initial trials showed that although both procedures established equivalent safety results, patients with chronic coronary occlusion, left main coronary stenosis, severely impaired left ventricular function or the need for valve surgery had a better outcome with bypass surgery. Recently published follow-up data (up to 8 years) of patients who were enrolled in the Bypass Angioplasty Revascularization Investigation (BARI) and Emory Angioplasty vs. Surgery Trial (EAST), which compared bypass surgery with balloon angioplasty in patients with multivessel disease, have shown that survival was virtually identical for non-diabetic patients (Figure 1). A survival benefit was evident only in diabetic patients who underwent surgical revascularization with internal mammary artery graft (Figure 2). Subgroup analysis of diabetic patients treated with saphenous vein grafts, including diabetics who were not on oral hypoglycemic or insulin treatment and non-diabetic patients, showed no difference in mortality. Furthermore, there was no significant difference among other high-risk subgroups, such as patients with reduced left ventricular function, triple-vessel disease, left anterior descending coronary artery disease or the those with the presence of type C lesions. Neither stents nor newer anti-platelet agents were used in these trials. The introduction of stents, which have shown to reduce the incidence of acute events, restenosis and urgent revascularization procedures and the use of newer surgical techniques have mandated a re-evaluation of these surgical and percutaneous techniques.
(Enlarge Image)
Long-term survival in non-diabetic patients who were enrolled in the Bypass Angioplasty Revascularization Investigation (BARI)[3] and Emory Angioplasty vs. Surgery Trial (EAST).[4]
(Enlarge Image)
Long-term survival in diabetic patients who were enrolled in the Bypass Angioplasty Revascularization Investigation (BARI)[3] and Emory Angioplasty vs. Surgery Trial (EAST).[4]
Two recently published studies have compared multivessel stented angioplasty and coronary bypass surgery. The Arterial Revascularization Therapies Study (ARTS) was a randomized, multicenter trial designed to compare the clinical outcomes between 1) coronary artery bypass surgery and 2) percutaneous coronary angioplasty and stenting in 1,205 patients. The primary endpoint was freedom from major adverse cardiac and cerebrovascular events (death, stroke, transient ischemic attacks, non-fatal myocardial infarction and revascularization procedures) for 12 months after randomization. The analysis incorporated data on the efficacy of the procedure, cost and cost-effectiveness, and quality of life at 30 days and at 1, 3 and 5 years. At 1-year follow-up, there were no significant differences between the two groups, in terms of mortality rates, stroke or myocardial infarction. Among those patients who did not experience myocardial infarction or stroke, a total of 16.8% in the stenting group and 3.5% in the surgical group underwent revascularization. Multivariate analysis showed that the presence of diabetes mellitus (19% of stented patients) was a key predictor of outcome, corroborating the BARI trial results. Conversely, coronary bypass graft surgery was significantly more expensive than stenting, by approximately $3,000 per patient.
The ERACI II study was a multicenter, randomized trial that compared stent-enhanced percutaneous coronary angioplasty with coronary artery bypass graft surgery. A total of 405 patients with multivessel disease underwent randomization to either percutaneous revascularization with stents versus conventional coronary artery bypass graft surgery. The composite primary endpoint was the occurrence of a major adverse cardiac event, defined as death, Q-wave myocardial infarction or stroke at 30 days. Follow-up was obtained at 1, 3 and 5 years. At long-term follow-up (18.5 ± 6.4 months), survival was 96.9% for patients randomized to the stented arm versus 92.5% for patients randomized to the surgical arm (p < 0.017). Similar to the previous studies, revascularization rates were higher in patients randomized to percutaneous intervention.
In this issue of the Journal of Invasive Cardiology, Villegas et al. report the results of a prospective registry. A total of 115 patients with multivessel disease (>= 60% stenosis of 3 major epicardial arteries) who were considered good candidates for either coronary artery surgery or multivessel stenting, underwent coronary artery stenting as an alternative to bypass surgery. Patients with complex lesions (Type C), small vessel disease (minimal lumen diameter < 2.5 mm) or left main disease were excluded from the study. Baseline clinical characteristics showed the usual risk factors, although there was a low percentage of diabetic patients (11%). The majority of patients (78%) were treated in a single stage, and the remaining patients (22%) were treated with a 1-week interval between the two stages. Despite the fact that this study was performed between 1996 and 1999, less than 2% of all patients were treated with glycoprotein IIb/IIIa inhibitors. During hospitalization, there were two deaths, five myocardial infarctions and one patient required emergency coronary bypass surgery. At 16 ± 14 months, follow-up (range 1-36 months), event-free survival was 71.3%. Two additional patients died (cumulative death rate of 3.4%), a total of 4.3% underwent bypass surgery and 20% underwent an additional revascularization procedure. Obviously, data from this registry cannot suggest whether bypass surgery can yield better clinical results. No separate analysis for diabetic patients was provided, but the small numbers of diabetic patients in this study prevent any significant conclusions on that issue.
Given the results of the study by Villegas et al., what have we learned? First, in a large population of patients with three-vessel disease, multiple stenting as an alternative to coronary bypass surgery is technically feasible and can be performed safely, with a high rate of procedural success and with a minimal incidence of peri-procedural and long-term complications. In addition, total stent length was proportionally related to higher target vessel revascularization rates. In 43% of the patients who underwent target vessel revascularization during the long-term follow-up, the total stent length was greater than 80 mm.
One often faces the need to stage the revascularization in patients with multivessel disease undergoing percutaneous coronary interventions. A staged approach, with a 1-week interval, was safely used in 20% of patients in the current study. Nikolsky et al. have recently analyzed data from our laboratory, regarding staging in patients with multivessel disease. Single-step procedures for multivessel disease was used in 129 patients and, compared to a staged approach, was used within 4-8 weeks in 135 patients. Both groups had similar rates of major adverse cardiac events during the in-hospital stay (2.2% vs. 4.6%; p = 0.28), although there was a trend towards fewer events in the staged arm at 1-year follow-up (26.1 vs. 35.9; p = 0.08). This is comparable to the 29% long-term (16 month) event rate in the current study. Importantly, a staging strategy with a 4-8 week interval was safe; no major adverse cardiac events occurred between the sessions. Restenosis was identified in 17% of patients during the second stage and was successfully re-treated in most of them. Our results are comparable to the experience of Villegas et al. and suggest that staging within 4-8 weeks may be used safely. The issue of optimization of treatment in patients with multivessel disease and the preferable strategy of treatment will have to be defined in the future by randomized clinical studies. Cost-effectiveness issues and patterns of local practice will have a major impact on therapeutic strategies, and will have to account for the major expected changes with the clinical introduction of drug eluting, antiproliferative stents in the near future.
In conclusion, three-vessel coronary artery disease is amenable to percutaneous treatment with stents. Results are comparable with those obtained with coronary artery bypass surgery, as well as by Villegas et al. and in the ARTS and ERACI II studies. The decision to perform percutaneous intervention in patients with diabetes mellitus and multivessel disease must be taken with caution, based on the long-term results of the BARI, EAST and ARTS studies. At present, both techniques are complementary. There is little doubt today that drug-eluting stents, which are "around the corner," will have a major impact on our approach to multivessel disease. With current revascularization patterns, we can be assured by the current trial and the other trials presented above that multivessel stenting is a safe procedure, and can replace bypass surgery at the cost of increased long-term revascularization rates.
Since 1977, when Gruentzig introduced balloon angioplasty as a less invasive alternative to coronary artery bypass graft surgery, the results have steadily improved. The proportion of complex patients who undergo this procedure has substantially increased, fueled by an unprecedented evolutionary change that has included the discovery of stents and the introduction of potent adjuvant pharmacological agents. Approximately 60% of all patients who undergo coronary artery revascularization via coronary artery bypass graft surgery or percutaneous intervention have multivessel disease that is amenable to treatment by either one of these procedures. Still, the most appropriate type of treatment for these patients is a matter of heated debate. In skilled hands, both techniques are relatively safe and highly effective in reducing angina, and have similar mortality and myocardial infarction rates, albeit fewer additional revascularization procedures in patients who undergo bypass surgery.
In the last decade, several randomized trials have compared percutaneous balloon angioplasty to coronary artery bypass surgery; these studies have shown that bypass surgery may prolong survival in a certain subset of patients. Initial trials showed that although both procedures established equivalent safety results, patients with chronic coronary occlusion, left main coronary stenosis, severely impaired left ventricular function or the need for valve surgery had a better outcome with bypass surgery. Recently published follow-up data (up to 8 years) of patients who were enrolled in the Bypass Angioplasty Revascularization Investigation (BARI) and Emory Angioplasty vs. Surgery Trial (EAST), which compared bypass surgery with balloon angioplasty in patients with multivessel disease, have shown that survival was virtually identical for non-diabetic patients (Figure 1). A survival benefit was evident only in diabetic patients who underwent surgical revascularization with internal mammary artery graft (Figure 2). Subgroup analysis of diabetic patients treated with saphenous vein grafts, including diabetics who were not on oral hypoglycemic or insulin treatment and non-diabetic patients, showed no difference in mortality. Furthermore, there was no significant difference among other high-risk subgroups, such as patients with reduced left ventricular function, triple-vessel disease, left anterior descending coronary artery disease or the those with the presence of type C lesions. Neither stents nor newer anti-platelet agents were used in these trials. The introduction of stents, which have shown to reduce the incidence of acute events, restenosis and urgent revascularization procedures and the use of newer surgical techniques have mandated a re-evaluation of these surgical and percutaneous techniques.
(Enlarge Image)
Long-term survival in non-diabetic patients who were enrolled in the Bypass Angioplasty Revascularization Investigation (BARI)[3] and Emory Angioplasty vs. Surgery Trial (EAST).[4]
(Enlarge Image)
Long-term survival in diabetic patients who were enrolled in the Bypass Angioplasty Revascularization Investigation (BARI)[3] and Emory Angioplasty vs. Surgery Trial (EAST).[4]
Two recently published studies have compared multivessel stented angioplasty and coronary bypass surgery. The Arterial Revascularization Therapies Study (ARTS) was a randomized, multicenter trial designed to compare the clinical outcomes between 1) coronary artery bypass surgery and 2) percutaneous coronary angioplasty and stenting in 1,205 patients. The primary endpoint was freedom from major adverse cardiac and cerebrovascular events (death, stroke, transient ischemic attacks, non-fatal myocardial infarction and revascularization procedures) for 12 months after randomization. The analysis incorporated data on the efficacy of the procedure, cost and cost-effectiveness, and quality of life at 30 days and at 1, 3 and 5 years. At 1-year follow-up, there were no significant differences between the two groups, in terms of mortality rates, stroke or myocardial infarction. Among those patients who did not experience myocardial infarction or stroke, a total of 16.8% in the stenting group and 3.5% in the surgical group underwent revascularization. Multivariate analysis showed that the presence of diabetes mellitus (19% of stented patients) was a key predictor of outcome, corroborating the BARI trial results. Conversely, coronary bypass graft surgery was significantly more expensive than stenting, by approximately $3,000 per patient.
The ERACI II study was a multicenter, randomized trial that compared stent-enhanced percutaneous coronary angioplasty with coronary artery bypass graft surgery. A total of 405 patients with multivessel disease underwent randomization to either percutaneous revascularization with stents versus conventional coronary artery bypass graft surgery. The composite primary endpoint was the occurrence of a major adverse cardiac event, defined as death, Q-wave myocardial infarction or stroke at 30 days. Follow-up was obtained at 1, 3 and 5 years. At long-term follow-up (18.5 ± 6.4 months), survival was 96.9% for patients randomized to the stented arm versus 92.5% for patients randomized to the surgical arm (p < 0.017). Similar to the previous studies, revascularization rates were higher in patients randomized to percutaneous intervention.
In this issue of the Journal of Invasive Cardiology, Villegas et al. report the results of a prospective registry. A total of 115 patients with multivessel disease (>= 60% stenosis of 3 major epicardial arteries) who were considered good candidates for either coronary artery surgery or multivessel stenting, underwent coronary artery stenting as an alternative to bypass surgery. Patients with complex lesions (Type C), small vessel disease (minimal lumen diameter < 2.5 mm) or left main disease were excluded from the study. Baseline clinical characteristics showed the usual risk factors, although there was a low percentage of diabetic patients (11%). The majority of patients (78%) were treated in a single stage, and the remaining patients (22%) were treated with a 1-week interval between the two stages. Despite the fact that this study was performed between 1996 and 1999, less than 2% of all patients were treated with glycoprotein IIb/IIIa inhibitors. During hospitalization, there were two deaths, five myocardial infarctions and one patient required emergency coronary bypass surgery. At 16 ± 14 months, follow-up (range 1-36 months), event-free survival was 71.3%. Two additional patients died (cumulative death rate of 3.4%), a total of 4.3% underwent bypass surgery and 20% underwent an additional revascularization procedure. Obviously, data from this registry cannot suggest whether bypass surgery can yield better clinical results. No separate analysis for diabetic patients was provided, but the small numbers of diabetic patients in this study prevent any significant conclusions on that issue.
Given the results of the study by Villegas et al., what have we learned? First, in a large population of patients with three-vessel disease, multiple stenting as an alternative to coronary bypass surgery is technically feasible and can be performed safely, with a high rate of procedural success and with a minimal incidence of peri-procedural and long-term complications. In addition, total stent length was proportionally related to higher target vessel revascularization rates. In 43% of the patients who underwent target vessel revascularization during the long-term follow-up, the total stent length was greater than 80 mm.
One often faces the need to stage the revascularization in patients with multivessel disease undergoing percutaneous coronary interventions. A staged approach, with a 1-week interval, was safely used in 20% of patients in the current study. Nikolsky et al. have recently analyzed data from our laboratory, regarding staging in patients with multivessel disease. Single-step procedures for multivessel disease was used in 129 patients and, compared to a staged approach, was used within 4-8 weeks in 135 patients. Both groups had similar rates of major adverse cardiac events during the in-hospital stay (2.2% vs. 4.6%; p = 0.28), although there was a trend towards fewer events in the staged arm at 1-year follow-up (26.1 vs. 35.9; p = 0.08). This is comparable to the 29% long-term (16 month) event rate in the current study. Importantly, a staging strategy with a 4-8 week interval was safe; no major adverse cardiac events occurred between the sessions. Restenosis was identified in 17% of patients during the second stage and was successfully re-treated in most of them. Our results are comparable to the experience of Villegas et al. and suggest that staging within 4-8 weeks may be used safely. The issue of optimization of treatment in patients with multivessel disease and the preferable strategy of treatment will have to be defined in the future by randomized clinical studies. Cost-effectiveness issues and patterns of local practice will have a major impact on therapeutic strategies, and will have to account for the major expected changes with the clinical introduction of drug eluting, antiproliferative stents in the near future.
In conclusion, three-vessel coronary artery disease is amenable to percutaneous treatment with stents. Results are comparable with those obtained with coronary artery bypass surgery, as well as by Villegas et al. and in the ARTS and ERACI II studies. The decision to perform percutaneous intervention in patients with diabetes mellitus and multivessel disease must be taken with caution, based on the long-term results of the BARI, EAST and ARTS studies. At present, both techniques are complementary. There is little doubt today that drug-eluting stents, which are "around the corner," will have a major impact on our approach to multivessel disease. With current revascularization patterns, we can be assured by the current trial and the other trials presented above that multivessel stenting is a safe procedure, and can replace bypass surgery at the cost of increased long-term revascularization rates.