Kazuya Kawai

Comparison of Everolimus-Eluting and Sirolimus-Eluting Coronary Stents 1-Year Outcomes from the Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial (RESET)

Background— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES ( P noninferiority<0.0001, and P superiority=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P =0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P noninferiority<0.0001, and P superiority=0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: . Unique identifier: [NCT01035450][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01035450&atom=%2Fcirculationaha%2F126%2F10%2F1225.atomBackground— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (Pnoninferiority<0.0001, and Psuperiority=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, Pnoninferiority<0.0001, and Psuperiority=0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Three-Year Outcomes After Sirolimus-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Disease Insights From the j-Cypher Registry

Background— Long-term outcomes after stenting of an unprotected left main coronary artery (ULMCA) with drug-eluting stents have not been addressed adequately despite the growing popularity of this procedure. Methods and Results— j-Cypher is a multicenter prospective registry of consecutive patients undergoing sirolimus-eluting stent implantation in Japan. Among 12 824 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 3 years was significantly higher in patients with ULMCA stenting (n=582) than in patients without ULMCA stenting (n=12 242; 14.6% versus 9.2%, respectively; P<0.0001); however, there was no significant difference between the 2 groups in the adjusted risk of death (hazard ratio 1.23, 95% confidence interval 0.95 to 1.60, P=0.12). Among 476 patients whose ULMCA lesions were treated exclusively with a sirolimus-eluting stent, patients with ostial/shaft lesions (n=96) compared with those with bifurcation lesions (n=380) had a significantly lower rate of target-lesion revascularization for the ULMCA lesions (3.6% versus 17.1%, P=0.005), with similar cardiac death rates at 3 years (9.8% versus 7.6%, P=0.41). Among patients with bifurcation lesions, patients with stenting of both the main and side branches (n=119) had significantly higher rates of cardiac death (12.2% versus 5.5%; P=0.02) and target-lesion revascularization (30.9% versus 11.1%; P<0.0001) than those with main-branch stenting alone (n=261). Conclusions— The higher unadjusted mortality rate of patients undergoing ULMCA stenting with a sirolimus-eluting stent did not appear to be related to ULMCA treatment itself but rather to the patients’ high-risk profile. Although long-term outcomes in patients with ostial/shaft ULMCA lesions were favorable, outcomes in patients with bifurcation lesions treated with stenting of both the main and side branches appeared unacceptable.

Safety and Efficacy of Sirolimus-Eluting Stent Implantation in Patients With Acute Coronary Syndrome in the Real World

The use of drug-eluting stents in patients with acute coronary syndrome (ACS), particularly those with acute myocardial infarction (AMI), is controversial owing to concerns about late adverse events. We evaluated the long-term safety of sirolimus-eluting stent implantation in patients with ACS. Of 10,778 patients treated exclusively with a sirolimus-eluting stent in the j-Cypher registry, the 3-year outcomes of 2,308 patients with ACS (953 patients with AMI) were compared to those of 8,470 patients without ACS. Compared to patients without ACS, the patients with ACS had a significantly greater adjusted risk of death or myocardial infarction (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.12 to 1.37, p <0.0001) and definite or probable stent thrombosis (HR 1.43, 95% CI 1.11 to 1.82, p = 0.006) within the first year after sirolimus-eluting stent implantation. However, after 1 year, patients with ACS no longer had a greater risk of death or myocardial infarction (HR 1.01, 95% CI 0.90 to 1.13, p = 0.87) and stent thrombosis (HR 1.32, 95% CI 0.92 to 1.86, p = 0.13). Of the patients with ACS, those with AMI had a greater risk of death or myocardial infarction (HR 1.33, 95% CI 1.12 to 1.6, p = 0.001) and stent thrombosis (HR 1.57, 95% CI 1.05 to 2.39, p = 0.03) than those with unstable angina pectoris within the first year. However, they had a similar risk of death or myocardial infarction (HR 1.00, 95% CI 0.78 to 1.22, p = 0.83) and stent thrombosis (HR 0.83, 95% CI 0.38 to 1.6, p = 0.59) after 1 year. The risk of late adverse events >1 year after sirolimus-eluting stent implantation was similar between those with and without ACS and between those with AMI and those with unstable angina pectoris.

Three-year outcome of sirolimus-eluting stent implantation in coronary bifurcation lesions: the provisional side branch stenting approach versus the elective two-stent approach.

AIMS To explore optimal management strategies for bifurcation lesions with sirolimus-eluting stents (SES). METHODS AND RESULTS Among 12,824 patients enrolled in the j-Cypher Registry, we identified 2,122 patients with 2,250 non-left main bifurcation lesions (average age: 69 years; diabetes: 39%; acute coronary syndrome: 24%; lesion length ≥30 mm: 17%; true bifurcation: 53%) treated exclusively with SES. The majority of lesions (1,978 lesions, 88%) were treated by provisional side branch stenting approach with a 4.5% crossover rate, while the elective two-stent approach (stenting both main and side branches) was adopted in 272 lesions. The 3-year incidence of target-lesion revascularisation (TLR) was significantly higher in the elective two-stent group than in the provisional group (18.5% vs. 9.8%, p<0.0001). The incidence of definite stent thrombosis was not different between the two groups (1.3% vs. 0.61%, p=0.21). Among 1,871 lesions with main branch stenting alone, final kissing balloon dilatation (FKB) was performed in 938 lesions (50%). The incidence of TLR was not different between the two groups with or without FKB (9.9% vs. 9.2%, p=0.98). CONCLUSIONS The provisional approach provided a good long-term outcome in the majority of lesions with low crossover rate to the two-stent approach. Lesions treated with FKB had similar TLR outcome to those without FKB after main branch stenting alone.

Comparison of 5-year outcomes in patients with and without unprotected left main coronary artery disease after treatment with sirolimus-eluting stents: insights from the j-Cypher registry.

OBJECTIVES This study assessed 5-year outcomes after implantation of sirolimus-eluting stents (SES) for unprotected left main coronary artery (ULMCA) disease in comparison with that for non-left main disease. BACKGROUND More information on long-term outcomes after ULMCA stenting is needed. METHODS The j-Cypher is a multicenter prospective registry of consecutive patients undergoing SES implantation in Japan. RESULTS Among 12,812 patients enrolled in the j-Cypher registry, the unadjusted mortality rate at 5 years was significantly higher in patients with ULMCA stenting than in patients without ULMCA stenting (22.8% vs. 14.1%; p < 0.0001); however, the risk for death with ULMCA stenting was no longer significant after adjusting for confounders (hazard ratio: 1.18, 95% confidence interval: 0.95 to 1.46; p = 0.14). In the lesion-level comparison, the nonbifurcation ULMCA lesions treated exclusively with SES had a significantly lower rate of target lesion revascularization (TLR) than those in non-ULMCA nonbifurcation lesions (2.4% vs. 12.7%; p = 0.04). Among bifurcation lesions, those treated with a provisional 2-stent approach had similar rates of TLR (12.1% vs. 11.4%; p = 0.79) between the ULMCA and non-ULMCA groups. Lesions treated with an elective 2-stent approach had higher TLR rates in the ULMCA group as compared with the non-ULMCA group (33.5% vs. 19.7%; p = 0.002). CONCLUSIONS The safety of ULMCA stenting relative to non-LMCA stenting was maintained through 5 years follow-up. In terms of efficacy, SES implantation in nonbifurcation ULMCA lesions was associated with an extremely low cumulative incidence of TLR, whereas the elective 2-stent approach for ULMCA bifurcation lesions was associated with a markedly higher cumulative incidence of TLR as compared with that for non-ULMCA bifurcation lesions.

Antiplatelet therapy discontinuation and stent thrombosis after sirolimus-eluting stent implantation: Five-year outcome of the j-Cypher Registry

BACKGROUND The influence of antiplatelet therapy discontinuation on the incidence of stent thrombosis, especially very late stent thrombosis, after drug-eluting stent implantation has not been yet fully addressed. METHODS Relationship between antiplatelet therapy discontinuation and stent thrombosis up to 5years was evaluated in 12,812 consecutive patients undergoing sirolimus-eluting stents (SES) implantation in the j-Cypher registry. Data on status of antiplatelet therapy during follow-up were collected prospectively. RESULTS Median follow-up interval was 1699days (interquartile range, 1184-1928days). Incidences of definite stent thrombosis were 0.34% at 30days, 0.55% at 1year, and 1.6% at 5years. Dual antiplatelet therapy was maintained in 97.4%, 63%, and 43.9% of patients at 30days, 1year, and 5years, respectively. The rates of stent thrombosis in patients who discontinued both thienopyridine and aspirin were significantly higher in the time intervals of 31-365days, 2-3years and 3-4years, and tended to be higher in the time intervals of 1-2years and 4-5years than those in patients who continued both (31-365days: 1.26% versus 0.2%, P<0.001; 1-2years: 0.59% versus 0.15%, P=0.06; 2-3years: 1.35% versus 0.2%, P=0.004; 3-4years: 1.09% versus 0.25%, P=0.0496; 4-5years: 1.35% versus 0.43%, P=0.17). Patients who discontinued either thienopyridine or aspirin only did not have an excess of stent thrombosis in any time intervals. CONCLUSIONS In conclusion, discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine or aspirin only, was associated with an increased incidence of late and very late stent thrombosis up to 5years after SES implantation.

Three-year follow-up outcomes of SES and PES in a randomized controlled study stratified by the presence of diabetes mellitus: J-DEsSERT trial

BACKGROUND Three-year clinical follow-up of patients with diabetes mellitus (DM) in the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) using 2 different drug eluting stents (DES). A recent study demonstrated that efficacy of sirolimus eluting stents (SES) attenuated over time in diabetic patients. METHODS In the largest trial of its kind, 1724 DM patients out of 3533 enrolled patients were randomized to either SES or paclitaxel eluting stents (PES). RESULTS There were no significant differences in baseline clinical characteristics aside from hypertension. Incidence of major adverse cardiac cerebrovascular events (MACCE) mainly due to higher target vessel failure (TVF) initially indicated a benefit in SES (MACCE rate at 1 year: SES 9.4%, PES 12.2%, p=0.08); however this had attenuated by the time of the 3-year follow-up (MACCE rate from 1 to 3 years: SES 8.4%, PES 6.1%, p=0.10). A similar pattern was observed in insulin-treated patients: MACCE rate from 1 to 3 years was 10.5% in SES and 6.4% in PES (p=0.25). Angiographic follow-up also resulted in higher major adverse cardiac event (MACE) rates at 1 year (presence 11.5%, absence 8.3%, p=0.04); however by 3 years rates were similar regardless of the presence of angiographic follow-up (MACE rate at 3 years: presence 16.0%, absence 14.5%, p=0.35). CONCLUSIONS The superiority of SES over PES in MACCE at 1 year had attenuated by 3-year follow-up. Eventually, the 3-year safety and efficacy profiles were similar regardless of insulin treatment.

Comparison of Everolimus-Eluting and Sirolimus-Eluting Coronary Stents

Background— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES ( P noninferiority<0.0001, and P superiority=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P =0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P noninferiority<0.0001, and P superiority=0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: . Unique identifier: [NCT01035450][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01035450&atom=%2Fcirculationaha%2F126%2F10%2F1225.atomBackground— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (Pnoninferiority<0.0001, and Psuperiority=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, Pnoninferiority<0.0001, and Psuperiority=0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI.

Second-Generation vs. First-Generation Drug-Eluting Stents in Patients With Calcified Coronary Lesions ― Pooled Analysis From the RESET and NEXT Trials ―

BACKGROUND The comparative efficacy of second-generation (G2) vs. first-generation (G1) drug-eluting stents (DES) for calcified coronary lesions is unknown.Methods and Results:We compared the 3-year clinical outcomes of patients with G1- or G2-DES according to the presence or absence of calcified coronary lesions as assessed in an angiographic core laboratory using data from 2 large-scale prospective multicenter randomized trials, RESET and NEXT. G1-DES and G2-DES were implanted in 299 and 1,033 patients, respectively, in the Calc stratum (≥1 lesion with moderate/severe calcification), and 1,208 and 3,550 patients, respectively, in the Non-calc stratum (no/mild calcification). The patients in the Calc stratum had a significantly higher adjusted risk for the primary outcome measure (any target-lesion revascularization (TLR)) than those in the Non-calc stratum (HR: 1.38, 95% CI: 1.11-1.71, P=0.004). The cumulative 3-year incidence of any TLR was not significantly different between the G1-DES and G2-DES groups in both the Calc and Non-calc strata (12.1% vs. 9.7%, P=0.22, and 6.8% vs. 6.1%, P=0.44, respectively). After adjusting for confounders, the effect of G2DES relative to G1-DES for any TLR remained insignificant in both the Calc and Non-calc strata (HR: 0.78, 95% CI: 0.48-1.25, P=0.3, and HR: 0.84, 95% CI: 0.61-1.17, P=0.31, respectively, P interaction=0.55). CONCLUSIONS The effect of G2-DES relative to G1-DES for TLR was not significantly different regardless of the presence or absence of lesion calcification.