CABG vs PCI: Outcomes With Multiple Arterial Bypass Grafting
CABG vs PCI: Outcomes With Multiple Arterial Bypass Grafting
A total of 8,402 multivessel CAD patients undergoing their primary revascularization were study-eligible and distributed as follows: BMS-PCI (n = 2,207; age 66.6 ± 11.9 years); DES-PCI (n = 2,381; age 65.9 ± 11.7 years); SA-CABG (n = 2,289; age 69.3 ± 9.0 years); and MA-CABG (n = 1,525; age 58.3 ± 8.7 years). Patient characteristics differed substantially for the different revascularization method cohorts (Table 1). Notably, MA-CABG patients were younger and more were male (80.3%), reflecting a practice selection; however, this has changed over the study period with both the median age (57.2 vs. 61.5 years) and proportion of women (17.7% vs. 24.7%) increasing between 1995 to 1996 and 2009 to 2011, respectively.
First coronary interventions amounted to 77% (9,242 of 11,999) of all unique PCI patients, whereas remaining patients had previous PCI (n = 1,526; 12.7%), CABG (n = 915; 7.6%), or both (n = 292; 2.4%) and thus were excluded from the analysis. A total of 4,588 (49.6%) of the primary (first-time) PCI patients met the inclusion criteria. The latter increased systematically over the study period (36% [1998] up to 60% [2008 to 2009]) (Online Figure 1 http://content.onlinejacc.org/data/Journals/JAC/934486/07060_mmc1.docx) and reflected a trend of more frequent use of PCI as a primary modality to treat multivessel CAD. BMS were used exclusively before 2003, whereas DES-PCI increased progressively after that to about 85% to 90% of all stent PCI by 2007 to 2009 (Online Figure 2 http://content.onlinejacc.org/data/Journals/JAC/934486/07060_mmc1.docx). The DES cohort in the present study included 1,833 first-generation (77%; 1:2 sirolimus to paclitaxel) and 548 second-generation (23%; 5:1 zotarolimus to everolimus) DES.
The unadjusted in-hospital mortality was comparable for BMS-PCI versus DES-PCI (12 of 2,207 [0.54%] vs. 4 of 2,381 [0.17%]; p = 0.057), but it was distinctly lower for the younger and healthier MA-CABG patients versus SA-CABG patients (4 of 1,525 [0.26%] vs. 38 of 2,289 [1.66%]; p < 0.001). Unadjusted Kaplan-Meier death-free survival differed substantially for the 4 treatment groups (p < 0.001 overall and pairwise) (Figure 1A). Here, MA-CABG (mean age: 58 years) exhibited the best 9-year survival and SA-CABG (69 years), the worst survival, whereas PCI patients showed intermediate survival with DES-PCI superior to survival with BMS-PCI.
(Enlarge Image)
Figure 1.
Survival After Percutaneous and Surgical CAD Treatment Modalities
Comparisons of unadjusted 9-year all-cause mortality (A) and unplanned reintervention-free (B) survival shown for all 4 coronary revascularization groups: 2,207 bare-metal stent (BMS) percutaneous coronary intervention (PCI) (age 66.6 ± 11.9 years); 2,381 drug-eluting stent (DES)-PCI (age 65.9 ± 11.7 years); 2,289 single-arterial (SA) coronary artery bypass graft (CABG) (age 69.3 ± 9.0 years); and 1,525 multiarterial (MA)-CABG (age 58.3 ± 8.7 years). The p values were derived by log-rank test. CAD = coronary artery disease.
Planned PCI were frequently used as part of a staged treatment approach given their multivessel disease (1,060 of 4,588; 23.1% overall), and this was more prevalent with the more recent DES-PCI (28.8% vs. 16.9%; p < 0.001). In contrast, unplanned reinterventions (PCI or CABG) were more frequent in BMS-PCI (21.5% vs. 15.8%; p < 0.001), but this may partly reflect their relatively longer follow-up. Both CABG modalities were associated with superior unadjusted, unplanned reintervention-free survival compared with rates for both BMS and DES groups, which had essentially identical 0 to 3 years unplanned reintervention outcomes (Figure 1B). Time-to-reintervention analysis showed a distinct change in the relative proportions and time course of the planned versus unplanned reintervention in BMS-PCI versus DES-PCI (Figures 2A and 2B). The relative decrease in unplanned reinterventions with DES probably reflects their superiority over BMS, whereas the increased planned PCI among DES reflect the changing practice patterns of interventional cardiologists in more recent years toward percutaneous treatment of more complex disease requiring multiple PCI.
(Enlarge Image)
Figure 2.
9-Year Mortality and Reintervention Outcomes for BMS- Versus DES-PCI
Breakdown of 9-year cumulative event rates to their all-cause mortality, planned reinterventions, and unplanned reinterventions for multivessel coronary artery disease patient cohorts treated with intracoronary stenting at their index (first) revascularization procedure: BMS-PCI cohort (A) and DES-PCI cohort (B). *Definition of planned PCI provided under Outcomes and Follow-up in the Methods section. Abbreviations as in Figure 1.
The number of matched patients, based on separate propensity score models, differed for the 4-pairwise comparisons: BMS-PCI versus SA-CABG (1,058 pairs); BMS-PCI versus MA-CABG (746 pairs); DES-PCI versus SA-CABG (667 pairs); and DES-PCI versus MA-CABG (546 pairs). Matching successfully identified comparison subcohorts with similar demographics, risk factors, and comorbidities (Online Tables 1 to 4 http://content.onlinejacc.org/data/Journals/JAC/934486/07060_mmc1.docx).
BMS-PCI was associated with worse death-free survival than SA-CABG was, especially for the first 7 years of follow-up (p = 0.015; mean age = 68 years; 73% 3-vessel disease) (Central Illustration), and to a greater extent when compared with survival rates for MA-CABG, which showed a 10% absolute BMS-PCI versus MA-CABG difference at 5 (85.2% vs. 95.0%) and 9 (76.3% vs. 86.9%) years (p < 0.001; mean age = 61 years; 82% 3-vessel disease) (Central Illustration). Alternatively, DES-PCI showed similar death-free survival as for SA-CABG, except for a modest SA-CABG advantage for the first 3 years (p = 0.615; mean age = 68 years; 78% 3-vessel disease) (Central Illustration). Lastly, DES-PCI exhibited worse mortality than MA-CABG did with death-free survival of 86.3% versus 95.6% at 5 years and 82.8% versus 89.8% at 9 years (p < 0.001; mean age = 60.4 years; 84% 3-vessel disease) (Central Illustration). Reintervention-free survival was substantially and significantly worse with PCI irrespective of stent type when compared with survival rates for either single arterial or multiarterial CABG (Figures 3A to 3D). The corresponding 9-year mortality HR estimates are summarized in Figure 4. Briefly, the surgery-to-BMS-PCI HR were in favor of CABG surgery approaching statistical significance in cases of SA-CABG (HR: 0.87; 95% CI: 0.75 to 1.02; p = 0.056) and were substantial and highly significant for MA-CABG versus BMS-PCI (HR: 0.38; 95% CI: 0.31 to 0.46; p < 0.001). Alternatively, DES-PCI and SA-CABG 9-year survival was comparable with a near-unity HR (HR: 1.06; 95% CI: 0.85 to 1.32; p = 0.615). Last, the MA-CABG versus DES-PCI survival advantage was substantial resulting in an HR of 0.45 (95% CI: 0.31 to 0.66) over the 9-year follow-up period (p < 0.001). These 9-year hazard estimates were essentially unchanged when further adjusted for the presence of left main disease and were also similar when derived by comprehensive risk-adjustment in all versus matched-only patients (Figure 4). Lastly, all 4 survival comparisons in propensity matched subcohorts (Central Illustration) exhibited significant time modification (interaction term) of the early versus late HR. Specifically, an early advantage of SA-CABG ≤3 years was lost when compared with the advantage of BMS, whereas it was completely reversed versus the advantage of DES. In case of MA-CABG, a more substantial advantage over either BMS or DES was sustained for a longer period (4.5 years) and was not reversed even if it lost significance (Table 2).
(Enlarge Image)
Figure 3.
Pairwise PCI Versus CABG Comparisons of Match-Adjusted Unplanned Reintervention
Comparison of 9-year propensity-matched reintervention-free survival data for both PCI treatment cohorts with each separately compared with SA-CABG and MA-CABG surgery: (A) BMS-PCI versus SA-CABG; (B) BMS-PCI versus MA-CABG; (C) DES-PCI versus SA-CABG; and (D) DES-PCI versus MA-CABG. The p values were derived by log-rank test. Abbreviations as in Figure 1.
(Enlarge Image)
Figure 4.
Pairwise Adjusted Hazard Ratios of CABG Versus PCI Modalities
Risk-adjusted 9-year all-cause mortality CABG-to-PCI hazard ratios derived for both the BMS-PCI and DES-PCI treatment cohorts when each is compared with the SA-CABG and MA-CABG surgical treatments. Solid squares reflect hazard ratios derived in matched patient cohorts (*additional adjustment for left main disease, which was not included in propensity models). Open squares reflect hazard ratios derived from all available patients using forced risk-adjustments (22 factors) via proportional hazard Cox regression. Pts = patients; other abbreviations as in Figure 1.
(Enlarge Image)
Central Illustration.
Optimal Revascularization of Multivessel CAD: Comparison of 9-Year Propensity Matched All-Cause Mortality Survival Data for Both PCI Treatment Cohorts
Each cohort is separately compared to single-arterial (SA) and multiarterial (MA) coronary artery bypass graft (CABG) surgery: (A) bare-metal stent (BMS) percutaneous coronary intervention (PCI) versus SA-CABG; (B) BMS-PCI versus MA-CABG; (C) drug-eluting stent (DES)-PCI versus SA-CABG; and (D) DES-PCI versus MA-CABG. The p values were derived by log-rank test. CAD = coronary artery disease.
Results
A total of 8,402 multivessel CAD patients undergoing their primary revascularization were study-eligible and distributed as follows: BMS-PCI (n = 2,207; age 66.6 ± 11.9 years); DES-PCI (n = 2,381; age 65.9 ± 11.7 years); SA-CABG (n = 2,289; age 69.3 ± 9.0 years); and MA-CABG (n = 1,525; age 58.3 ± 8.7 years). Patient characteristics differed substantially for the different revascularization method cohorts (Table 1). Notably, MA-CABG patients were younger and more were male (80.3%), reflecting a practice selection; however, this has changed over the study period with both the median age (57.2 vs. 61.5 years) and proportion of women (17.7% vs. 24.7%) increasing between 1995 to 1996 and 2009 to 2011, respectively.
PCI Trends
First coronary interventions amounted to 77% (9,242 of 11,999) of all unique PCI patients, whereas remaining patients had previous PCI (n = 1,526; 12.7%), CABG (n = 915; 7.6%), or both (n = 292; 2.4%) and thus were excluded from the analysis. A total of 4,588 (49.6%) of the primary (first-time) PCI patients met the inclusion criteria. The latter increased systematically over the study period (36% [1998] up to 60% [2008 to 2009]) (Online Figure 1 http://content.onlinejacc.org/data/Journals/JAC/934486/07060_mmc1.docx) and reflected a trend of more frequent use of PCI as a primary modality to treat multivessel CAD. BMS were used exclusively before 2003, whereas DES-PCI increased progressively after that to about 85% to 90% of all stent PCI by 2007 to 2009 (Online Figure 2 http://content.onlinejacc.org/data/Journals/JAC/934486/07060_mmc1.docx). The DES cohort in the present study included 1,833 first-generation (77%; 1:2 sirolimus to paclitaxel) and 548 second-generation (23%; 5:1 zotarolimus to everolimus) DES.
Unadjusted Outcomes
The unadjusted in-hospital mortality was comparable for BMS-PCI versus DES-PCI (12 of 2,207 [0.54%] vs. 4 of 2,381 [0.17%]; p = 0.057), but it was distinctly lower for the younger and healthier MA-CABG patients versus SA-CABG patients (4 of 1,525 [0.26%] vs. 38 of 2,289 [1.66%]; p < 0.001). Unadjusted Kaplan-Meier death-free survival differed substantially for the 4 treatment groups (p < 0.001 overall and pairwise) (Figure 1A). Here, MA-CABG (mean age: 58 years) exhibited the best 9-year survival and SA-CABG (69 years), the worst survival, whereas PCI patients showed intermediate survival with DES-PCI superior to survival with BMS-PCI.
(Enlarge Image)
Figure 1.
Survival After Percutaneous and Surgical CAD Treatment Modalities
Comparisons of unadjusted 9-year all-cause mortality (A) and unplanned reintervention-free (B) survival shown for all 4 coronary revascularization groups: 2,207 bare-metal stent (BMS) percutaneous coronary intervention (PCI) (age 66.6 ± 11.9 years); 2,381 drug-eluting stent (DES)-PCI (age 65.9 ± 11.7 years); 2,289 single-arterial (SA) coronary artery bypass graft (CABG) (age 69.3 ± 9.0 years); and 1,525 multiarterial (MA)-CABG (age 58.3 ± 8.7 years). The p values were derived by log-rank test. CAD = coronary artery disease.
Planned PCI were frequently used as part of a staged treatment approach given their multivessel disease (1,060 of 4,588; 23.1% overall), and this was more prevalent with the more recent DES-PCI (28.8% vs. 16.9%; p < 0.001). In contrast, unplanned reinterventions (PCI or CABG) were more frequent in BMS-PCI (21.5% vs. 15.8%; p < 0.001), but this may partly reflect their relatively longer follow-up. Both CABG modalities were associated with superior unadjusted, unplanned reintervention-free survival compared with rates for both BMS and DES groups, which had essentially identical 0 to 3 years unplanned reintervention outcomes (Figure 1B). Time-to-reintervention analysis showed a distinct change in the relative proportions and time course of the planned versus unplanned reintervention in BMS-PCI versus DES-PCI (Figures 2A and 2B). The relative decrease in unplanned reinterventions with DES probably reflects their superiority over BMS, whereas the increased planned PCI among DES reflect the changing practice patterns of interventional cardiologists in more recent years toward percutaneous treatment of more complex disease requiring multiple PCI.
(Enlarge Image)
Figure 2.
9-Year Mortality and Reintervention Outcomes for BMS- Versus DES-PCI
Breakdown of 9-year cumulative event rates to their all-cause mortality, planned reinterventions, and unplanned reinterventions for multivessel coronary artery disease patient cohorts treated with intracoronary stenting at their index (first) revascularization procedure: BMS-PCI cohort (A) and DES-PCI cohort (B). *Definition of planned PCI provided under Outcomes and Follow-up in the Methods section. Abbreviations as in Figure 1.
Matched-adjusted Comparisons
The number of matched patients, based on separate propensity score models, differed for the 4-pairwise comparisons: BMS-PCI versus SA-CABG (1,058 pairs); BMS-PCI versus MA-CABG (746 pairs); DES-PCI versus SA-CABG (667 pairs); and DES-PCI versus MA-CABG (546 pairs). Matching successfully identified comparison subcohorts with similar demographics, risk factors, and comorbidities (Online Tables 1 to 4 http://content.onlinejacc.org/data/Journals/JAC/934486/07060_mmc1.docx).
BMS-PCI was associated with worse death-free survival than SA-CABG was, especially for the first 7 years of follow-up (p = 0.015; mean age = 68 years; 73% 3-vessel disease) (Central Illustration), and to a greater extent when compared with survival rates for MA-CABG, which showed a 10% absolute BMS-PCI versus MA-CABG difference at 5 (85.2% vs. 95.0%) and 9 (76.3% vs. 86.9%) years (p < 0.001; mean age = 61 years; 82% 3-vessel disease) (Central Illustration). Alternatively, DES-PCI showed similar death-free survival as for SA-CABG, except for a modest SA-CABG advantage for the first 3 years (p = 0.615; mean age = 68 years; 78% 3-vessel disease) (Central Illustration). Lastly, DES-PCI exhibited worse mortality than MA-CABG did with death-free survival of 86.3% versus 95.6% at 5 years and 82.8% versus 89.8% at 9 years (p < 0.001; mean age = 60.4 years; 84% 3-vessel disease) (Central Illustration). Reintervention-free survival was substantially and significantly worse with PCI irrespective of stent type when compared with survival rates for either single arterial or multiarterial CABG (Figures 3A to 3D). The corresponding 9-year mortality HR estimates are summarized in Figure 4. Briefly, the surgery-to-BMS-PCI HR were in favor of CABG surgery approaching statistical significance in cases of SA-CABG (HR: 0.87; 95% CI: 0.75 to 1.02; p = 0.056) and were substantial and highly significant for MA-CABG versus BMS-PCI (HR: 0.38; 95% CI: 0.31 to 0.46; p < 0.001). Alternatively, DES-PCI and SA-CABG 9-year survival was comparable with a near-unity HR (HR: 1.06; 95% CI: 0.85 to 1.32; p = 0.615). Last, the MA-CABG versus DES-PCI survival advantage was substantial resulting in an HR of 0.45 (95% CI: 0.31 to 0.66) over the 9-year follow-up period (p < 0.001). These 9-year hazard estimates were essentially unchanged when further adjusted for the presence of left main disease and were also similar when derived by comprehensive risk-adjustment in all versus matched-only patients (Figure 4). Lastly, all 4 survival comparisons in propensity matched subcohorts (Central Illustration) exhibited significant time modification (interaction term) of the early versus late HR. Specifically, an early advantage of SA-CABG ≤3 years was lost when compared with the advantage of BMS, whereas it was completely reversed versus the advantage of DES. In case of MA-CABG, a more substantial advantage over either BMS or DES was sustained for a longer period (4.5 years) and was not reversed even if it lost significance (Table 2).
(Enlarge Image)
Figure 3.
Pairwise PCI Versus CABG Comparisons of Match-Adjusted Unplanned Reintervention
Comparison of 9-year propensity-matched reintervention-free survival data for both PCI treatment cohorts with each separately compared with SA-CABG and MA-CABG surgery: (A) BMS-PCI versus SA-CABG; (B) BMS-PCI versus MA-CABG; (C) DES-PCI versus SA-CABG; and (D) DES-PCI versus MA-CABG. The p values were derived by log-rank test. Abbreviations as in Figure 1.
(Enlarge Image)
Figure 4.
Pairwise Adjusted Hazard Ratios of CABG Versus PCI Modalities
Risk-adjusted 9-year all-cause mortality CABG-to-PCI hazard ratios derived for both the BMS-PCI and DES-PCI treatment cohorts when each is compared with the SA-CABG and MA-CABG surgical treatments. Solid squares reflect hazard ratios derived in matched patient cohorts (*additional adjustment for left main disease, which was not included in propensity models). Open squares reflect hazard ratios derived from all available patients using forced risk-adjustments (22 factors) via proportional hazard Cox regression. Pts = patients; other abbreviations as in Figure 1.
(Enlarge Image)
Central Illustration.
Optimal Revascularization of Multivessel CAD: Comparison of 9-Year Propensity Matched All-Cause Mortality Survival Data for Both PCI Treatment Cohorts
Each cohort is separately compared to single-arterial (SA) and multiarterial (MA) coronary artery bypass graft (CABG) surgery: (A) bare-metal stent (BMS) percutaneous coronary intervention (PCI) versus SA-CABG; (B) BMS-PCI versus MA-CABG; (C) drug-eluting stent (DES)-PCI versus SA-CABG; and (D) DES-PCI versus MA-CABG. The p values were derived by log-rank test. CAD = coronary artery disease.