CABG vs PCI in Patients With 3-Vessel Disease
Of the 1800 patients randomized in the SYNTAX trial, 1095 patients had 3VD. Of these, 549 were randomly assigned to CABG and 546 to PCI. There were no differences between treatment groups in terms of age, gender, presence of cardiac risk factors and associated comorbidities, or expected surgical mortality as assessed by the logistic EuroSCORE (Table 1). The extent and complexity of CAD were also evenly distributed between the two groups. The majority of patients underwent elective revascularization with no differences between groups.
Patients randomized to CABG had significantly longer waiting times for the procedure as opposed to PCI (Table 2). Procedure times and post-procedural hospital stay for patients who underwent CABG were significantly longer than those who underwent PCI.
Amongst patients randomized to CABG, off-pump surgery was performed in only 13.9% of patients. Bilateral internal mammary arteries were used in 30.6% of patients, with total arterial revascularization being performed in 17.0% of patients. The mean number of grafts and distal anastomoses per patient were 2.9 ± 0.7 and 3.4 ± 0.8, respectively. Patients undergoing PCI received a mean of 5.3 ± 2.1 stents with a mean stent length of 99.4 ± 45.5 mm per patient. A total stent length of >100 mm was implanted in >40% of patients. Patients who underwent CABG less commonly had IR; however, it did not reach statistical significance.
Patients who underwent PCI generally received more secondary preventive medication during follow-up than those who underwent CABG. Antiplatelet therapy was given more frequently in the PCI group at all time points, and at 5 years was still significantly higher following PCI than CABG for administration of a thienopyridine (36.7 vs. 11.0%, respectively; P < 0.001) and dual antiplatelet therapy (20.8 vs. 6.4%, respectively; P < 0.001). The use of other medications was exclusively higher after PCI during the first year of follow-up, but at 5 years rates were comparable between PCI and CABG: beta-blockers (75.7 vs. 76.1%, respectively; P = 0.90), ACE-inhibitors (55.2 vs. 52.9%, respectively; P = 0.49), calcium-channel blockers (25.4 vs. 22.3%, respectively; P = 0.28), angiotensin II-receptor antagonists (20.3 vs. 20.9%, respectively; P = 0.82), and statins (83.2 vs. 85.3%, respectively; P = 0.40) (Supplementary material online, Table S1).
Pre-procedural MACCE was 0.7% (n = 4) in the CABG group and 0.2% (n = 1) in the PCI group (P = 0.38). A total of 19 patients died within 30 days after revascularization: 12 after PCI and 7 after CABG (P = 0.28) (Table 2). Although the stroke rate was non-significantly higher after CABG (P = 0.10), MI and repeat revascularization occurred significantly more frequently after PCI. The rate of MACCE at 30 days was comparable between PCI and CABG (7.0 vs. 4.8%, respectively; P = 0.064).
At 5 years follow-up, 88% of CABG-randomized and 96% of PCI-randomized 3VD patients were available for analysis (see Supplementary material online, Figure S1). Overall, the occurrence of MACCE at 5 years was significantly higher in patients who underwent PCI when compared with those who underwent CABG [37.5 (n = 123) vs. 24.2% (n = 201), respectively; P < 0.001] (Figure 1A). Similarly, the composite safety endpoint of death/stroke/MI was more commonly observed after PCI than after CABG [22.0 (n = 118) vs. 14.0% (n = 71), respectively; P < 0.001] (Figure 1B), with the difference driven by significantly higher rates of all-cause death [14.6 (n = 78) vs. 9.2% (n = 46), respectively; P = 0.006] and MI [10.6 (n = 55) vs. 3.3% (n = 17), respectively; P < 0.001] (Figures 1C and E). Furthermore, patients had significantly higher rates of cardiac death after PCI vs. CABG [9.2 (n = 48) vs. 4.0% (n = 20), respectively; hazard ratio (HR) 2.34, 95% CI 1.39–3.95; P < 0.001]. Patients required repeat revascularization more frequently after PCI than after CABG [25.4 (n = 130) vs. 12.6% (n = 61), respectively; P < 0.001] (Figure 1F), driven by significant differences in both repeat PCI [21.5 (n = 110) vs. 12.3% (n = 59), respectively; HR 1.96, 95% CI 1.41–2.65; P < 0.001] and repeat CABG [5.6 (n = 28) vs. 1.0% (n = 5), respectively; HR 5.56, 95% CI 2.15–14.41; P < 0.001]. Graft occlusion after surgery occurred in 18 patients (3.7%), resulting in an MI in 3 patients, repeat revascularization in 12 patients, and 3 patients required no treatment; there were no deaths. Thirty PCI patients (5.8%) experienced ST; of these, 9 patients died, 11 experienced an MI, and 10 underwent repeat revascularization. Occurrence of angina was also significantly higher at all time points after PCI than after CABG (Figure 2).
(Enlarge Image)
Figure 1.
Five-year estimates of adverse events. Kaplan–Meier curves for (A) MACCE, (B) all-cause death/stroke/MI, (C) all-cause death, (D) stroke, (E) MI, and (F) repeat revascularization. Bars represent ±1.5 standard error. P-values from log-rank test. CABG, coronary artery bypass grafting; CI, confidence interval; HR, hazard ratio; PCI, percutaneous coronary intervention; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction.
(Enlarge Image)
Figure 2.
Presence of angina during follow-up. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention.
In the sensitivity analysis, assuming all patients who were lost to follow-up or withdrew consent had an event, MACCE remained significantly higher after PCI than after CABG (40.7 vs. 34.6%, respectively; HR 1.23, 95% CI 1.01–1.49; P = 0.040), although there was no longer a difference in the composite of all-cause death/stroke/MI (26.0 vs. 26.6%, respectively; HR 0.96, 95% CI 0.76–1.21; P = 0.72).
The multivariable proportional hazard model revealed treatment with PCI to be an independent predictor of MACCE over 5-year follow-up (HR 1.66, 95% CI 1.32–2.09; P < 0.001), in addition to several pre-operative patient characteristics and IR (Table 3). Furthermore, treatment with PCI not only remained a significant independent predictor of the composite safety endpoint (HR 1.81, 95% CI 1.33–2.46; P < 0.001) but also of all-cause death (HR 1.81, 95% CI 1.24–2.67; P = 0.002).
Medically Treated Diabetes. Overall, 296 patients (CABG, n = 143 and PCI, n = 153) with 3VD had medically treated diabetes (Figure 3A). The MACCE rates in diabetic patients with 3VD were significantly higher in the PCI group than the CABG group (HR 2.30, 95% CI 1.50–3.55; P < 0.001). Significantly higher event rates were also seen after PCI vs. CABG in the composite safety endpoint of death/stroke/MI, all-cause death, MI, and repeat revascularization. Stroke rates were comparable. Although the differences in event rates among non-diabetic patients (CABG, n = 406 and PCI, n = 393) were smaller between groups, PCI in comparison with CABG still had significantly higher rates of MACCE (HR 1.51, 95% CI 1.15–1.96; P = 0.002), the composite safety endpoint, MI, and repeat revascularization, but with similar rates of all-cause death and stroke (Figure 3B). There were no significant treatment-by-diabetes interactions.
(Enlarge Image)
Figure 3.
Five-year estimates of adverse events in patients with diabetes (A) and without diabetes (B). Treatment-by-diabetes interactions failed to reach statistical significance for MACCE (P=0.095), the composite safety endpoint (P=0.44), all-cause death (P = 0.37), stroke (P = 0.63), MI (P = 0.88), and repeat revascularization (P = 0.15). Values are Kaplan–Meier event rates with P-values from log-rank test. CABG, coronary artery bypass grafting; composite, composite safety endpoint of all-cause death/stroke/MI; PCI, percutaneous coronary intervention; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction.
SYNTAX Terciles. Differences in event rates between PCI and CABG showed a step-wise increase with increasing SYNTAX scores for all events, except stroke, for which no differences were observed through all SYNTAX score terciles (Figure 4). For patients with a low SYNTAX score (0–22), no significant differences were noted between PCI and CABG treatment groups in rates of MACCE, the composite safety endpoint of death/stroke/MI, all-cause death, and MI. Patients who underwent PCI did have a significantly higher rate of repeat revascularization than those who underwent CABG. Patients with intermediate (23–33) or high SYNTAX scores (≥33), patients who underwent CABG had significantly lower rates of MACCE, the composite safety endpoint of death/stroke/MI, as well as individual components all-cause death, MI and repeat revascularization (Figure 4). There was no evidence of significant treatment-by-SYNTAX score tercile interaction.
(Enlarge Image)
Figure 4.
Five-year estimates of adverse events according to the SYNTAX score. (A) MACCE, (B) the composite safety endpoint of all-cause death/stroke/MI, (C) all-cause death, (D) stroke, (E) MI, and (F) repeat revascularization. Treatment-by-SYNTAX score tercile interactions failed to reach statistical significance for MACCE (P = 0.12), the composite safety endpoint (P = 0.085), all-cause death (P = 0.15), stroke (P = 0.12), MI (P = 0.16), and repeat revascularization (P = 0.32). Values are Kaplan–Meier event rates with P-values from log-rank test. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction.
Incomplete Revascularization. In the CABG cohort, outcomes were similar in patients with complete and IR (Table 4). Conversely, in the PCI cohort, patients who underwent incomplete as opposed to complete revascularization had significantly higher rates of MACCE (42.6 vs. 32.7%, respectively; P = 0.010) and repeat revascularization (30.6 vs. 20.4%, respectively; P = 0.003). However, occurrence of the composite of death/stroke/MI and its individual endpoints were similar (Table 4). There were no significant interactions between completeness of revascularization and treatment.
Results
Baseline Characteristics
Of the 1800 patients randomized in the SYNTAX trial, 1095 patients had 3VD. Of these, 549 were randomly assigned to CABG and 546 to PCI. There were no differences between treatment groups in terms of age, gender, presence of cardiac risk factors and associated comorbidities, or expected surgical mortality as assessed by the logistic EuroSCORE (Table 1). The extent and complexity of CAD were also evenly distributed between the two groups. The majority of patients underwent elective revascularization with no differences between groups.
Procedural Characteristics
Patients randomized to CABG had significantly longer waiting times for the procedure as opposed to PCI (Table 2). Procedure times and post-procedural hospital stay for patients who underwent CABG were significantly longer than those who underwent PCI.
Amongst patients randomized to CABG, off-pump surgery was performed in only 13.9% of patients. Bilateral internal mammary arteries were used in 30.6% of patients, with total arterial revascularization being performed in 17.0% of patients. The mean number of grafts and distal anastomoses per patient were 2.9 ± 0.7 and 3.4 ± 0.8, respectively. Patients undergoing PCI received a mean of 5.3 ± 2.1 stents with a mean stent length of 99.4 ± 45.5 mm per patient. A total stent length of >100 mm was implanted in >40% of patients. Patients who underwent CABG less commonly had IR; however, it did not reach statistical significance.
Patients who underwent PCI generally received more secondary preventive medication during follow-up than those who underwent CABG. Antiplatelet therapy was given more frequently in the PCI group at all time points, and at 5 years was still significantly higher following PCI than CABG for administration of a thienopyridine (36.7 vs. 11.0%, respectively; P < 0.001) and dual antiplatelet therapy (20.8 vs. 6.4%, respectively; P < 0.001). The use of other medications was exclusively higher after PCI during the first year of follow-up, but at 5 years rates were comparable between PCI and CABG: beta-blockers (75.7 vs. 76.1%, respectively; P = 0.90), ACE-inhibitors (55.2 vs. 52.9%, respectively; P = 0.49), calcium-channel blockers (25.4 vs. 22.3%, respectively; P = 0.28), angiotensin II-receptor antagonists (20.3 vs. 20.9%, respectively; P = 0.82), and statins (83.2 vs. 85.3%, respectively; P = 0.40) (Supplementary material online, Table S1).
Pre-procedural MACCE was 0.7% (n = 4) in the CABG group and 0.2% (n = 1) in the PCI group (P = 0.38). A total of 19 patients died within 30 days after revascularization: 12 after PCI and 7 after CABG (P = 0.28) (Table 2). Although the stroke rate was non-significantly higher after CABG (P = 0.10), MI and repeat revascularization occurred significantly more frequently after PCI. The rate of MACCE at 30 days was comparable between PCI and CABG (7.0 vs. 4.8%, respectively; P = 0.064).
Five-year Outcomes
At 5 years follow-up, 88% of CABG-randomized and 96% of PCI-randomized 3VD patients were available for analysis (see Supplementary material online, Figure S1). Overall, the occurrence of MACCE at 5 years was significantly higher in patients who underwent PCI when compared with those who underwent CABG [37.5 (n = 123) vs. 24.2% (n = 201), respectively; P < 0.001] (Figure 1A). Similarly, the composite safety endpoint of death/stroke/MI was more commonly observed after PCI than after CABG [22.0 (n = 118) vs. 14.0% (n = 71), respectively; P < 0.001] (Figure 1B), with the difference driven by significantly higher rates of all-cause death [14.6 (n = 78) vs. 9.2% (n = 46), respectively; P = 0.006] and MI [10.6 (n = 55) vs. 3.3% (n = 17), respectively; P < 0.001] (Figures 1C and E). Furthermore, patients had significantly higher rates of cardiac death after PCI vs. CABG [9.2 (n = 48) vs. 4.0% (n = 20), respectively; hazard ratio (HR) 2.34, 95% CI 1.39–3.95; P < 0.001]. Patients required repeat revascularization more frequently after PCI than after CABG [25.4 (n = 130) vs. 12.6% (n = 61), respectively; P < 0.001] (Figure 1F), driven by significant differences in both repeat PCI [21.5 (n = 110) vs. 12.3% (n = 59), respectively; HR 1.96, 95% CI 1.41–2.65; P < 0.001] and repeat CABG [5.6 (n = 28) vs. 1.0% (n = 5), respectively; HR 5.56, 95% CI 2.15–14.41; P < 0.001]. Graft occlusion after surgery occurred in 18 patients (3.7%), resulting in an MI in 3 patients, repeat revascularization in 12 patients, and 3 patients required no treatment; there were no deaths. Thirty PCI patients (5.8%) experienced ST; of these, 9 patients died, 11 experienced an MI, and 10 underwent repeat revascularization. Occurrence of angina was also significantly higher at all time points after PCI than after CABG (Figure 2).
(Enlarge Image)
Figure 1.
Five-year estimates of adverse events. Kaplan–Meier curves for (A) MACCE, (B) all-cause death/stroke/MI, (C) all-cause death, (D) stroke, (E) MI, and (F) repeat revascularization. Bars represent ±1.5 standard error. P-values from log-rank test. CABG, coronary artery bypass grafting; CI, confidence interval; HR, hazard ratio; PCI, percutaneous coronary intervention; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction.
(Enlarge Image)
Figure 2.
Presence of angina during follow-up. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention.
In the sensitivity analysis, assuming all patients who were lost to follow-up or withdrew consent had an event, MACCE remained significantly higher after PCI than after CABG (40.7 vs. 34.6%, respectively; HR 1.23, 95% CI 1.01–1.49; P = 0.040), although there was no longer a difference in the composite of all-cause death/stroke/MI (26.0 vs. 26.6%, respectively; HR 0.96, 95% CI 0.76–1.21; P = 0.72).
Predictors of 5-year Outcomes
The multivariable proportional hazard model revealed treatment with PCI to be an independent predictor of MACCE over 5-year follow-up (HR 1.66, 95% CI 1.32–2.09; P < 0.001), in addition to several pre-operative patient characteristics and IR (Table 3). Furthermore, treatment with PCI not only remained a significant independent predictor of the composite safety endpoint (HR 1.81, 95% CI 1.33–2.46; P < 0.001) but also of all-cause death (HR 1.81, 95% CI 1.24–2.67; P = 0.002).
Subgroup Analyses of 5-year Outcomes
Medically Treated Diabetes. Overall, 296 patients (CABG, n = 143 and PCI, n = 153) with 3VD had medically treated diabetes (Figure 3A). The MACCE rates in diabetic patients with 3VD were significantly higher in the PCI group than the CABG group (HR 2.30, 95% CI 1.50–3.55; P < 0.001). Significantly higher event rates were also seen after PCI vs. CABG in the composite safety endpoint of death/stroke/MI, all-cause death, MI, and repeat revascularization. Stroke rates were comparable. Although the differences in event rates among non-diabetic patients (CABG, n = 406 and PCI, n = 393) were smaller between groups, PCI in comparison with CABG still had significantly higher rates of MACCE (HR 1.51, 95% CI 1.15–1.96; P = 0.002), the composite safety endpoint, MI, and repeat revascularization, but with similar rates of all-cause death and stroke (Figure 3B). There were no significant treatment-by-diabetes interactions.
(Enlarge Image)
Figure 3.
Five-year estimates of adverse events in patients with diabetes (A) and without diabetes (B). Treatment-by-diabetes interactions failed to reach statistical significance for MACCE (P=0.095), the composite safety endpoint (P=0.44), all-cause death (P = 0.37), stroke (P = 0.63), MI (P = 0.88), and repeat revascularization (P = 0.15). Values are Kaplan–Meier event rates with P-values from log-rank test. CABG, coronary artery bypass grafting; composite, composite safety endpoint of all-cause death/stroke/MI; PCI, percutaneous coronary intervention; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction.
SYNTAX Terciles. Differences in event rates between PCI and CABG showed a step-wise increase with increasing SYNTAX scores for all events, except stroke, for which no differences were observed through all SYNTAX score terciles (Figure 4). For patients with a low SYNTAX score (0–22), no significant differences were noted between PCI and CABG treatment groups in rates of MACCE, the composite safety endpoint of death/stroke/MI, all-cause death, and MI. Patients who underwent PCI did have a significantly higher rate of repeat revascularization than those who underwent CABG. Patients with intermediate (23–33) or high SYNTAX scores (≥33), patients who underwent CABG had significantly lower rates of MACCE, the composite safety endpoint of death/stroke/MI, as well as individual components all-cause death, MI and repeat revascularization (Figure 4). There was no evidence of significant treatment-by-SYNTAX score tercile interaction.
(Enlarge Image)
Figure 4.
Five-year estimates of adverse events according to the SYNTAX score. (A) MACCE, (B) the composite safety endpoint of all-cause death/stroke/MI, (C) all-cause death, (D) stroke, (E) MI, and (F) repeat revascularization. Treatment-by-SYNTAX score tercile interactions failed to reach statistical significance for MACCE (P = 0.12), the composite safety endpoint (P = 0.085), all-cause death (P = 0.15), stroke (P = 0.12), MI (P = 0.16), and repeat revascularization (P = 0.32). Values are Kaplan–Meier event rates with P-values from log-rank test. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction.
Incomplete Revascularization. In the CABG cohort, outcomes were similar in patients with complete and IR (Table 4). Conversely, in the PCI cohort, patients who underwent incomplete as opposed to complete revascularization had significantly higher rates of MACCE (42.6 vs. 32.7%, respectively; P = 0.010) and repeat revascularization (30.6 vs. 20.4%, respectively; P = 0.003). However, occurrence of the composite of death/stroke/MI and its individual endpoints were similar (Table 4). There were no significant interactions between completeness of revascularization and treatment.
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