Noboru Nishiwaki

Comparison of Long-Term Outcome After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Unprotected Left Main Coronary Artery Disease (from the CREDO-Kyoto PCI/CABG Registry Cohort-2)

The long-term outcome of percutaneous coronary intervention (PCI) compared to coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease (ULMCAD) remains to be investigated. We identified 1,005 patients with ULMCAD of 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Cumulative 3-year incidence of a composite of death/myocardial infarction (MI)/stroke was significantly higher in the PCI group than in the CABG group (22.7% vs 14.8%, p = 0.0006, log-rank test). However, the adjusted outcome was not different between the PCI and CABG groups (hazard ratio [HR] 1.30, 95% confidence interval [CI] 0.79 to 2.15, p = 0.30). Stratified analysis using the SYNTAX score demonstrated that risk for a composite of death/MI/stroke was not different between the 2 treatment groups in patients with low (<23) and intermediate (23 to 33) SYNTAX scores (adjusted HR 1.70, 95% CI 0.77 to 3.76, p = 0.19; adjusted HR 0.86, 95% CI 0.37 to 1.99, p = 0.72, respectively), whereas in patients with a high SYNTAX score (≥33), it was significantly higher after PCI than after CABG (adjusted HR 2.61, 95% CI 1.32 to 5.16, p = 0.006). In conclusion, risk of PCI for serious adverse events seemed to be comparable to that after CABG in patients with ULMCAD with a low or intermediate SYNTAX score, whereas PCI compared with CABG was associated with a higher risk for serious adverse events in patients with a high SYNTAX score.

Comparison of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Unprotected Left Main Coronary Artery Disease – 5-Year Outcome From CREDO-Kyoto PCI/CABG Registry Cohort-2 –

BACKGROUND Studies evaluating long-term (≥5 years) outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease (ULMCAD) are still limited, despite concerns for late adverse events after drug-eluting stents implantation. METHODS AND RESULTS We identified 1,004 patients with ULMCAD (PCI: n=364, CABG: n=640) among 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2. The primary outcome measure in the current analysis was a composite of death, myocardial infarction, and stroke (death/MI/stroke). The cumulative 5-year incidence of and the adjusted risk for death/MI/stroke were significantly higher in the PCI group than in the CABG group (34.5% vs. 24.1%, log-rank P<0.001, adjusted hazard ratio (HR): 1.48 [95% confidence interval (CI): 1.07-2.05, P=0.02]). The adjusted risks for all-cause death was not significantly different between the 2 groups. Regarding the stratified analysis by the SYNTAX score, the adjusted risk for death/MI/stroke was not significantly different between the 2 groups in patients with low (<23) or intermediate (23-33) SYNTAX score, whereas it was significantly higher in the PCI group than in the CABG group in patients with high (≤33) SYNTAX score. CONCLUSIONS CABG as compared with PCI was associated with better long-term outcome in patients with ULMCAD, especially those with high anatomical complexity.

Three-year outcome after percutaneous coronary intervention and coronary artery bypass grafting in patients with triple-vessel coronary artery disease: observations from the CREDO-Kyoto PCI/CABG registry cohort-2.

AIMS We sought to investigate medium-term outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with triple-vessel coronary artery disease (TVD). METHODS AND RESULTS We identified 2,981 patients with TVD (PCI: N=1,825, CABG: N=1,156) among 15,939 patients with first coronary revascularisation enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2. Excess adjusted three-year risk of the PCI group relative to the CABG group for death/myocardial infarction (MI)/stroke was significant (HR 1.47 [95% CI: 1.13-1.92, p=0.004]). Adjusted risk for all-cause death was also significantly higher with PCI as compared with CABG (HR 1.62 [95% CI: 1.16-2.27, p=0.005]), while risk for cardiac death was neutral between the two groups (HR 1.3 [95% CI: 0.81-2.07, p=0.28]). PCI was also associated with a markedly higher risk for any coronary revascularisation. Regarding the analysis stratified by the SYNTAX score, the adjusted HR of PCI relative to CABG for death/MI/stroke was 1.66 (95% CI: 1.04-2.65, p=0.03) in the low-score (<23: N=874, and N=257), 1.24 (95% CI: 0.83-1.85, p=0.29) in the intermediate-score (23-32: N=638, and N=388), and 1.59 (95% CI: 0.998-2.54, p=0.051) in the high-score (≥ 33: N=280, and N=375) tertiles, respectively. CONCLUSIONS PCI as compared with CABG was associated with significantly higher risk for serious adverse events in TVD patients.

Comparison of five-year outcomes of coronary artery bypass grafting versus percutaneous coronary intervention in patients with left ventricular ejection fractions≤50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).

Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF≤50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all-cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%<LVEF≤50%) and severe (LVEF≤35%) LV systolic dysfunction, the risk of cardiac death after PCI was significantly greater than that after CABG (hazard ratio 2.25, 95% confidence interval 1.15 to 4.40, p=0.02 and hazard ratio 4.42, 95% confidence interval 1.48 to 13.24, p=0.01). Similarly, the risk of all-cause death tended to be greater after PCI than after CABG in both patients with moderate and severe LV systolic dysfunction without significant interaction (hazard ratio 1.57, 95% confidence interval 0.96 to 2.56, p=0.07 and hazard ratio 1.42, 95% confidence interval 0.71 to 2.82, p=0.32; interaction p=0.91). CABG was associated with better 5-year survival outcomes than PCI in patients with impaired LV systolic function (LVEF≤50%) with complex coronary disease in the era of drug-eluting stents. In both patients with moderate (35%<LVEF≤50%) and severe (LVEF≤35%) LV systolic dysfunction, CABG tended to have better survival outcomes than PCI.

Five-Year Outcomes of Percutaneous Versus Surgical Coronary Revascularization in Patients With Diabetes Mellitus (from the CREDO-Kyoto PCI/CABG Registry Cohort-2)

We investigated the impact of diabetes mellitus on long-term outcomes of percutaneous coronary intervention (PCI) in the drug-eluting stent era versus coronary artery bypass grafting (CABG) in a real-world population with advanced coronary disease. We identified 3,982 patients with 3-vessel and/or left main disease of 15,939 patients with first coronary revascularization enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2 (patients without diabetes: n = 1,984 [PCI: n = 1,123 and CABG: n = 861], and patients with diabetes: n = 1,998 [PCI: n = 1,065 and CABG: n = 933]). Cumulative 5-year incidence of all-cause death after PCI was significantly higher than after CABG both in patients without and with diabetes (19.8% vs 16.2%, p = 0.01, and 22.9% vs 19.0%, p = 0.046, respectively). After adjusting confounders, the excess mortality risk of PCI relative to CABG was no longer significant (hazard ratio [HR] 1.16; 95% confidence interval [CI] 0.88 to 1.54; p = 0.29) in patients without diabetes, whereas it remained significant (HR 1.31; 95% CI 1.01 to 1.70; p = 0.04) in patients with diabetes. The excess adjusted risks of PCI relative to CABG for cardiac death, myocardial infarction (MI), and any coronary revascularization were significant in both patients without (HR 1.59, 95% CI 1.01 to 2.51, p = 0.047; HR 2.16, 95% CI 1.20 to 3.87, p = 0.01; and HR 3.30, 95% CI 2.55 to 4.25, p <0.001, respectively) and with diabetes (HR 1.45, 95% CI 1.00 to 2.51, p = 0.047; HR 2.31, 95% CI 1.31 to 4.08, p = 0.004; and HR 3.70, 95% CI 2.91 to 4.69, p <0.001, respectively). There was no interaction between diabetic status and the effect of PCI relative to CABG for all-cause death, cardiac death, MI, and any revascularization. In conclusion, in both patients without and with diabetes with 3-vessel and/or left main disease, CABG compared with PCI was associated with better 5-year outcomes in terms of cardiac death, MI, and any coronary revascularization. There was no difference in the direction and magnitude of treatment effect of CABG relative to PCI regardless of diabetic status.

Increased isoprostane content in coronary plaques obtained from vulnerable patients.

8-Iso-prostaglandin F(2)(alpha) (8-iso-PGF(2)(alpha)), a representative isoprostane, is a reliable biomarker for enhanced oxidant stress in vivo. Its urinary excretion has been proposed as a risk marker in patients with coronary heart disease. Isoprostane content has not yet been well elucidated so far in human coronary plaques. The aim of this study was to evaluate content of immunoreactive 8-iso-PGF(2)(alpha) in directional coronary atherectomy (DCA) specimens from patients with coronary heart diseases. Twenty-seven patients with stable angina pectoris (SAP) and 8 vulnerable patients (5 patients with unstable angina pectoris and 3 with recent myocardial infarction) were subjected to DCA. The specimens from SAP consisted of 14 de novo and 13 restenotic lesions, whereas those from the vulnerable patients were all de novo lesions. Total 8-iso-PGF(2)(alpha) content in the DCA specimens from the vulnerable patients was significantly greater than that from patients with SAP (5.48 (2.70-10.43) versus 2.38 (1.19-4.32)ng/g tissue, median (interquartile range), P<0.05). There was no significant difference in total 8-iso-PGF(2)(alpha) content between de novo and restenotic lesions from patients with SAP (3.25 (1.48-5.05) versus 1.57 (0.62-2.47)ng/g tissue, respectively, P=0.895). Total 8-iso-PGF(2)(alpha) content in apparently normal peripheral artery specimens was only 0.34 (0.26-0.46)ng/g tissue. In conclusion, 8-iso-PGF(2)(alpha) was enriched in the DCA specimens from vulnerable patients, suggesting a crucial role of free radicals in formation of vulnerable plaques and a putative benefit of anti-oxidant therapy on these patients.

Clinical Efficacy of Thrombus Aspiration on 5‐Year Clinical Outcomes in Patients With ST‐Segment Elevation Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Background Adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long-term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Methods and Results The CREDO-Kyoto AMI Registry is a large-scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005–2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5-year incidence of all-cause death was significantly lower in the TA group than in the non-TA group (18.5% versus 23.9%, log-rank P<0.001). After adjusting for confounders, however, the risk for all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target-lesion revascularization were also not significantly different between the 2 groups. Conclusions Adjunctive TA during primary PCI was not associated with better 5-year mortality in STEMI patients.

Impact of statin therapy on patients with coronary heart disease and aortic aneurysm or dissection

OBJECTIVE The impact of statin therapy on cardiovascular outcome in coronary artery disease (CAD) patients with aortic aneurysm or dissection (AD) is still unclear. The aim of this study was to elucidate the effect of statins at discharge to improve outcomes in CAD patients with AD. METHODS Among 14,834 consecutive patients who underwent first coronary revascularization in the CREDO-Kyoto PCI/CABG registry, we identified 699 patients (4.7%) with AD. The primary outcome measure was defined as a composite of all-cause death, myocardial infarction, and stroke. The effect of statin therapy was assessed by a Cox proportional hazards model incorporating clinically relevant factors. RESULTS The risk for the primary outcome measure was significantly higher in patients with AD (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.23-1.66; P < .0001). In patients with AD, 215 patients (31%) had already undergone aneurysm repair, and only 274 patients (39%) were treated with statins at discharge. Patients treated with statins were younger, had higher body mass index, and were more often treated with percutaneous coronary intervention. Heart failure, anemia, and hemodialysis were more prevalent in patients treated without statins. In patients without AD, 7014 patients (50%) were treated with statins. Patients treated with statins were younger and had higher body mass index, and more patients were treated for CAD due to myocardial infarction. Heart failure, prior stroke, hemodialysis, anemia, and malignant disease were more prevalent in patients treated without statins. The use of statins was associated with lower risk for the primary outcome measure in patients with AD (adjusted HR, 0.71; 95% CI, 0.51-0.99; P = .045) as well as in patients without AD (adjusted HR, 0.79; 95% CI, 0.73-0.85; P < .0001). The effect size of statin use was similar between the patients with AD and those without AD (P interaction = .69). CONCLUSIONS CAD patients with AD had significantly higher long-term risk for cardiovascular events. Statin therapy was associated with lower risk for cardiovascular events in patients with CAD with AD as well as in patients without AD.

Effects of Age and Sex on Clinical Outcomes after Percutaneous Coronary Intervention Relative to Coronary Artery Bypass Grafting in Patients with Triple Vessel Coronary Artery Disease

Background— Age and sex are important considerations in the choice between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in daily clinical practice. Methods and Results— Of 25 816 patients enrolled in the multicenter Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto; Cohort-1, n=9877; Cohort-2, n=15 939), the present study population consisted of 5651 patients (men, n=3998; women, n=1653) with triple-vessel coronary artery disease who were considered to be pertinent in comparisons of PCI with CABG (PCI, n=3165; CABG, n=2486). Patients were divided into 3 groups according to the tertiles of age: ⩽65 years (n=1972), 66 to 73 years (n=1820), and ≥74 years (n=1859). The excess adjusted mortality risk of PCI relative to CABG was significant in patients ≥74 years of age (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.10–1.79; P=0.006), whereas the risks were neutral in patients ⩽65 years of age (HR, 1.05; 95% CI, 0.73–1.53; P=0.78) and in patients 66 to 73 years of age (HR, 1.03; 95% CI, 0.78–1.36; P=0.85; interaction P=0.003). The excess mortality risk of PCI relative to CABG was significant in men (HR, 1.24; 95% CI, 1.03–1.50; P=0.02) and trended to be significant in women (HR, 1.34; 95% CI, 0.98–1.84; P=0.07) without significant interaction between sex and the mortality risk of PCI relative to CABG (interaction P=0.40). Conclusions— There was a significant association between age and the mortality risk of PCI relative to CABG with excess risk in patients ≥74 years of age and neutral risk in younger patients. There was no significant sex-related difference in the mortality risk of PCI relative to CABG.

Comparison of Five-Year Outcome of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Triple-Vessel Coronary Artery Disease (from the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2)

Studies evaluating long-term (≥5 years) outcomes of percutaneous coronary intervention (PCI) using drug-eluting stents compared with coronary artery bypass grafting (CABG) in patients with triple-vessel coronary artery disease (TVD) are still limited. We identified 2,978 patients with TVD (PCI: n = 1,824, CABG: n = 1,154) of 15,939 patients with first coronary revascularization enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2. The primary outcome measure in the present analysis was a composite of death, myocardial infarction (MI), and stroke. Median follow-up duration for the surviving patients was 1,973 days (interquartile range 1,700 to 2,244). The cumulative 5-year incidence of death/MI/stroke was significantly higher in the PCI group than in the CABG group (28.2% vs 24.0%, log-rank p = 0.006). After adjusting for confounders, the excess risk of PCI relative to CABG for death/MI/stroke remained significant (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.13 to 1.68, p = 0.002). The excess risks of PCI relative to CABG for all-cause death, MI, and any coronary revascularization were also significant (HR 1.38, 95% CI 1.10 to 1.74, p = 0.006; HR 2.81, 95% CI 1.69 to 4.66, p <0.001; and HR 4.10, 95% CI 3.32 to 5.06, p <0.001, respectively). The risk for stroke was not significantly different between the PCI and CABG groups (HR 0.88, 95% CI 0.61 to 1.26, p = 0.48). There were no interactions for the primary outcome measure between the mode of revascularization (PCI or CABG) and the subgroup factors such as age, diabetes, and Synergy Between PCI With Taxus and Cardiac Surgery score. In conclusion, CABG compared with PCI was associated with better long-term outcome in patients with TVD.