Yoon Haeng Cho

Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients With Diabetes Mellitus: The DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients)

OBJECTIVES We sought to evaluate the impact of cilostazol on neointimal hyperplasia after drug-eluting stent (DES) implantation in patients with diabetes mellitus (DM). BACKGROUND Although cilostazol has reduced the extent of neointimal hyperplasia and restenosis in patients after bare-metal stent implantation, it is not known whether this effect occurs after DES implantation in diabetic patients. METHODS This randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol, triple group, n = 200) and dual antiplatelet therapy (aspirin and clopidogrel, standard group, n = 200) for 6 months in patients with DM receiving DES. The primary end point was in-stent late loss at 6 months. RESULTS The 2 groups had similar baseline clinical and angiographic characteristics. The in-stent (0.25 +/- 0.53 mm vs. 0.38 +/- 0.54 mm, p = 0.025) and in-segment (0.42 +/- 0.50 mm vs. 0.53 +/- 0.49 mm, p = 0.031) late loss were significantly lower in the triple versus standard group, as were 6-month in-segment restenosis (8.0% vs. 15.6%, p = 0.033) and 9-month target lesion revascularization (TLR) (2.5% vs. 7.0%, p = 0.034). At 9 months, major adverse cardiac events, including death, myocardial infarction, and TLR, tended to be lower in the triple than in the standard group (3.0% vs. 7.0%, p = 0.066). Multivariate analysis showed that sirolimus-eluting stents and the use of cilostazol were strong predictors of reduced restenosis or TLR. CONCLUSIONS Triple antiplatelet therapy after DES implantation decreased angiographic restenosis and extent of late loss, resulting in a reduced risk of 9-month TLR compared with dual antiplatelet therapy in diabetic patients.

Sirolimus-eluting stent versus paclitaxel-eluting stent for patients with long coronary artery disease.

Background— Outcomes remain relatively unfavorable for stent-based coronary intervention of lesions with long diseased segments. This study compared sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) for long coronary lesions. Methods and Results— The present randomized, multicenter, prospective study compared the use of long (≥32 mm) SES with PES in 500 patients with long (≥25 mm) native coronary lesions. The primary end point of the trial was the rate of binary in-segment restenosis according to follow-up angiography at 6 months. The SES and PES groups had similar baseline characteristics. Lesion length was 33.9±11.6 mm in the SES group and 34.5±12.6 mm in the PES group (P=0.527). The in-segment binary restenosis rate was significantly lower in the SES group than in the PES group (3.3% versus 14.6%; relative risk 0.23; P<0.001). In-stent late loss of lumen diameter was 0.09±0.37 mm in the SES group and 0.45±0.55 mm in the PES group (P<0.001). In patients with restenoses, a pattern of focal restenosis was more common in the SES group than in the PES group (100% versus 53.3%, P=0.031). Consequently, SES patients had a lower rate of target-lesion revascularization at 9 months (2.4% versus 7.2%, P=0.012). The incidence of death (0.8% in SES versus 0% in PES, P=0.499) or myocardial infarction (8.8% in SES versus 10.8% in PES, P=0.452) at 9 months of follow-up was not statistically different between the 2 groups. Conclusions— For patients with long native coronary artery disease, SES implantation was associated with a reduced incidence of angiographic restenosis and a reduced need for target-lesion revascularization compared with PES implantation.

A Randomized Comparison of Sirolimus- Versus Paclitaxel-Eluting Stent Implantation in Patients With Diabetes Mellitus

OBJECTIVES The aim of this study was to compare the effectiveness of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM). BACKGROUND Drug-eluting stent implantation significantly improved the angiographic and clinical outcomes compared with bare-metal stent implantation in diabetic patients. However, comparison of SES with PES in diabetic patients has not been sufficiently evaluated. METHODS This prospective, multicenter, randomized study compared SES (n = 200) and PES implantation (n = 200) for diabetic patients (n = 400). The primary end point was in-segment restenosis at 6 months according to intention-to-treat principle. RESULTS The 2 groups had similar baseline clinical and angiographic characteristics. Six-month in-stent (3.4% vs. 18.2%, p < 0.001) and in-segment restenosis (4.0% vs. 20.8%, p < 0.001) and 9-month target lesion revascularization (2.0% vs. 7.5%, p = 0.017) were significantly lower in the SES versus the PES group. The incidence of death (0% in SES vs. 0.5% in PES, p = 0.999) or myocardial infarction (0.5% in SES vs. 0.5% in PES, p = 0.999) at 9-month follow-up was not statistically different between the 2 groups. Major adverse cardiac events including death, myocardial infarction, and target lesion revascularization at 9 months (2.0% vs. 8.0%, p = 0.010) were lower in the SES versus the PES group. CONCLUSIONS Sirolimus-eluting stent implantation is superior in reducing angiographic restenosis and improving 9-month clinical outcomes in patients with DM and coronary artery disease compared with PES implantation.

Randomized Comparison of Everolimus-Eluting Stent Versus Sirolimus-Eluting Stent Implantation for De Novo Coronary Artery Disease in Patients With Diabetes Mellitus (ESSENCE-DIABETES) Results From the ESSENCE-DIABETES Trial

Background— Drug-eluting stents significantly improved angiographic and clinical outcomes compared with bare metal stents in diabetic patients. However, a comparison of everolimus-eluting stents and sirolimus-eluting stents in diabetic patients has not been evaluated. Therefore we compared effectiveness of everolimus-eluting stents and sirolimus-eluting stents in patients with diabetes mellitus. Methods and Results— This prospective, multicenter, randomized study compared everolimus-eluting stent (n=149) and sirolimus-eluting stent (n=151) implantation in diabetic patients. The primary end point was noninferiority of angiographic in-segment late loss at 8 months. Clinical events were also monitored for at least 12 months. Everolimus-eluting stents were noninferior to sirolimus-eluting stents for 8-month in-segment late loss (0.23±0.27 versus 0.37±0.52 mm; difference, −0.13 mm; 95% confidence interval, −0.25 to −0.02; upper 1-sided 95% confidence interval, −0.04; P<0.001 for noninferiority), with reductions in in-stent restenosis (0% versus 4.7%; P=0.029) and in-segment restenosis (0.9% versus 6.5%; P=0.035). However, in-stent late loss (0.11±0.26 versus 0.20±0.49 mm; P=0.114) was not statistically different between the 2 groups. At 12 months, ischemia-driven target lesion revascularization (0.7% versus 2.6%; P=0.317), death (1.3% versus 3.3%; P=0.448), and myocardial infarction (0% versus 1.3%; P=0.498) were not statistically different between the 2 groups. Major adverse cardiac events, including death, myocardial infarction, and ischemia-driven target lesion revascularization (2.0% versus 5.3%; P=0.218), were also not statistically different between the 2 groups. Conclusions— Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00997763.

A Randomized, Double-Blind, Multicenter Comparison Study of Triple Antiplatelet Therapy With Dual Antiplatelet Therapy to Reduce Restenosis After Drug-Eluting Stent Implantation in Long Coronary Lesions: Results From the DECLARE-LONG II (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions) Trial

OBJECTIVES The purpose of this study was to determine whether cilostazol reduces intimal hyperplasia in patients undergoing long zotarolimus-eluting stent implantation (stent length: ≥ 30 mm) for native long coronary lesions (length: ≥ 25 mm). BACKGROUND Restenosis after drug-eluting stent implantation remains a significant clinical problem in long coronary lesions. METHODS Patients (n = 499) were assigned randomly to triple (aspirin, clopidogrel, and cilostazol, triple group: n = 250) or dual antiplatelet therapy (aspirin and clopidogrel and placebo, dual group: n = 249) for 8 months after long zotarolimus-eluting stent implantation. The primary end point was in-stent late loss at the 8-month angiography according to the intention-to-treat principle. RESULTS The 2 groups had similar baseline characteristics. The in-stent (0.56 ± 0.55 mm vs. 0.68 ± 0.59 mm, p = 0.045) and in-segment (0.32 ± 0.54 mm vs. 0.47 ± 0.54 mm, p = 0.006) late loss were significantly lower in the triple versus dual group, as were 8-month in-stent restenosis (10.8% vs. 19.1%, p = 0.016), in-segment restenosis (12.2% vs. 20.0%, p = 0.028), and 12-month ischemic-driven target lesion revascularization (5.2% vs. 10.0%, p = 0.042) rates. At 12 months, major adverse cardiac events including death, myocardial infarction, and ischemic-driven target lesion revascularization tended to be lower in the triple group than the dual group (7.2% vs. 12.0%, p = 0.07). Percent intimal hyperplasia volume by volumetric intravascular ultrasound analysis was reduced from 27.1 ± 13.2% for the dual group to 22.1 ± 9.9% for the triple group (p = 0.017). CONCLUSIONS Patients receiving triple antiplatelet therapy after long zotarolimus-eluting stent implantation had decreased extent of late luminal loss, percent intimal hyperplasia volume, and angiographic restenosis, resulting in a reduced risk of 12-month target lesion revascularization compared with patients receiving dual antiplatelet therapy. (Triple Versus Dual Antiplatelet Therapy after ABT578-Eluting Stent; NCT00589927).

Comparison of the Efficacy and Safety of Zotarolimus-, Sirolimus-, and Paclitaxel-Eluting Stents in Patients With ST-Elevation Myocardial Infarction

Drug-eluting stents (DESs) are increasingly used for treatment of acute ST-segment elevation myocardial infarction (STEMI), but there are few comparisons of outcomes of various types of DES. We compared the efficacy and safety of zotarolimus-eluting stents (ZESs), sirolimus-eluting stents (SESs), and paclitaxel-eluting stents (PESs) in primary intervention for STEMI. This multicenter, prospectively randomized ZEST-AMI trial included 328 patients at 12 medical centers who were randomly assigned to ZES (n = 108), SES (n = 110), or PES (n = 110) deployment. The primary end point was major adverse cardiac events (death, MI, and ischemia-driven target vessel revascularization) at 12 months. Secondary end points included the individual components of the primary end point, late loss, angiographic restenosis, and stent thrombosis. Baseline clinical and angiographic characteristics were well matched. In-segment late loss (0.28 +/- 0.42 vs 0.46 +/- 0.48 vs 0.47 +/- 0.50 mm, respectively, p = 0.029) and restenosis rate (2.7% vs 15.9% vs 12.3%, respectively, p = 0.027) at 8 months were lowest in the SES group compared to the ZES and PES groups. At 12 months, cumulative incidence rates of primary end points in the ZES, SES, and PES groups were 11.3%, 8.2%, and 8.2%, respectively (p = 0.834). There were 2 acute (in the SES group) and 5 subacute (2 in the SES group and 3 in the PES group) stent thromboses. Incidence of death, recurrent MI, or ischemia-driven target vessel revascularization did not differ among the 3 groups. In conclusion, despite the difference in restenosis rate, the efficacy and safety of the 3 different DESs showed similar, acceptable results in the treatment of STEMI.

Comparison of Triple Antiplatelet Therapy and Dual Antiplatelet Therapy in Patients at High Risk of Restenosis After Drug–Eluting Stent Implantation (from the DECLARE-DIABETES and -LONG Trials)

Although cilostazol has decreased restenosis and target lesion revascularization (TLR) after drug-eluting stent implantation, it is not known if this effect is durable at 2 years. We analyzed 2 randomized studies (Drug-Eluting stenting followed by Cilostazol treatment reduces LAte REstenosis in patients with DIABETES mellitus and Drug-Eluting Stenting Followed by Cilostazol treatment reduces LAte REstenosis in patients with LONG native coronary lesions trials) in which 900 patients were randomly assigned to triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol; triple group, n = 450) and dual antiplatelet therapy (aspirin and clopidogrel; standard group, n = 450) for 6 months in patients with diabetes or long lesions receiving drug-eluting stents. We evaluated 2-year major adverse cardiac events (MACEs) including death, myocardial infarction (MI), and TLR. Nine-month TLRs and MACEs were significantly decreased in the triple versus standard group. At 2 years, the triple group sowed significantly decreased TLRs (4.2% vs 9.1%, hazard ratio 0.45, 95% confidence interval 0.26 to 0.78, p = 0.004) and MACEs (5.6% vs 10.4%, hazard ratio 0.52, 95% confidence interval 0.32 to 0.84, p = 0.008) compared to the standard group with no differences in death and MI. In subgroup analysis, triple antiplatelet therapy decrease of 2-year TLR was favorable in all subgroups, especially in patients with paclitaxel-eluting stents, diabetes mellitus, small vessels, long lesions, and left anterior descending coronary artery lesions. In conclusion, compared to the standard group, initial benefit in decreases of 9-month TLRs and MACEs in the triple group was sustained at 2 years with no differences in death or MI. Triple antiplatelet therapy decrease of 2-year TLR was favorable in all subgroups, especially in patients with high-risk profiles.

A randomized comparison of sirolimus- versus paclitaxel-eluting stent implantation in patients with diabetes mellitus 2-year clinical outcomes of the DES-DIABETES trial.

To the Editor: The presence of diabetes mellitus has been associated with an increased risk of restenosis and unfavorable clinical outcomes in the era of bare-metal stents (BMS) or drug-eluting stents (DES). Previous studies found sirolimus-eluting stents (SES) to have greater efficacy than

Preventive Strategies of Renal Insufficiency in Patients With Diabetes Undergoing Intervention or Arteriography (the PREVENT Trial)

Few studies have compared the ability of sodium bicarbonate plus N-acetylcysteine (NAC) and sodium chloride plus NAC to prevent contrast-induced nephropathy (CIN) in diabetic patients with impaired renal function undergoing coronary or endovascular angiography or intervention. Diabetic patients (n = 382) with renal disease (serum creatinine ≥1.1 mg/dl and estimated glomerular filtration rate <60 ml/min/1.73 m(2)) were randomly assigned to receive prophylactic sodium chloride (saline group, n = 189) or sodium bicarbonate (bicarbonate group, n = 193) before elective coronary or endovascular angiography or intervention. All patients received oral NAC 1,200 mg 2 times/day for 2 days. The primary end point was CIN, defined as an increase in serum creatinine >25% or an absolute increase in serum creatinine ≥0.5 mg/dl within 48 hours after contrast exposure. There were no significant between-group differences in baseline characteristics. The primary end point was met in 10 patients (5.3%) in the saline group and 17 (9.0%) in the bicarbonate group (p = 0.17), with 2 (1.1%) and 4 (2.1%), respectively, requiring hemodialysis (p = 0.69). Rates of death, myocardial infarction, and stroke did not differ significantly at 1 month and 6 months after contrast exposure. In conclusion, hydration with sodium bicarbonate is not superior to hydration with sodium chloride in preventing CIN in patients with diabetic nephropathy undergoing coronary or endovascular angiography or intervention.

Comparison of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent for De Novo Coronary Artery DisEase in Patients With DIABETES Mellitus from the ESSENCE-DIABETES II Trial

Angiographic and clinical outcomes remain relatively unfavorable for diabetic patients even after the use of drug-eluting stent. This prospective, multicenter, randomized study compared the relative efficacy and safety of resolute zotarolimus-eluting stent (R-ZES) and sirolimus-eluting stent (SES) implantation in diabetic patients with coronary artery disease. The primary end point was noninferiority of angiographic in-segment late loss at 9 months. Clinical events were also monitored for at least 12 months. Patient recruitment was prematurely stopped after enrollment of 256 patients (127 in R-ZES group and 129 in SES) because of discontinuing production of SES. The R-ZES was noninferior to the SES for 9-month in-segment late loss (0.34 ± 0.30 vs 0.39 ± 0.43 mm; difference -0.048; 95% confidence interval -0.157 to 0.061; upper 1-sided 95% confidence interval 0.044; p <0.001 for noninferiority). In addition, in-stent late loss (0.22 ± 0.29 vs 0.21 ± 0.40 mm, p = 0.849) and the rates of in-segment (1.2% vs 6.7%, p = 0.119) and in-stent (1.2% vs 3.3%, p = 0.621) binary restenoses were similar between the 2 groups. At 12 months, there were no statistical differences between the 2 groups in the incidence of any clinical outcomes (death, myocardial infarction, stent thrombosis, ischemia-driven target lesion revascularization, ischemia-driven target vessel revascularization, and composite outcomes). In conclusion, despite having reduced power because of early study termination, our study suggests that the R-ZES has noninferior angiographic outcomes at 9 months to the SES in diabetic patients with coronary artery disease.