One-year results of the CRISTAL Trial, a randomized comparison of cypher sirolimus-eluting coronary stents versus balloon angioplasty for restenosis of drug-eluting stents.

OBJECTIVES: We compared the efficacy of the Cypher Select (Cordis Corporation, Bridgewater, NJ, USA) sirolimus-eluting stent (SES) versus balloon angioplasty (BA) in in-stent restenosis (ISR) of Taxus or Taxus Liberté paclitaxel-eluting stents (PES; Boston Scientific, Natick, MA, USA) or Cypher/Cypher Select SES. BACKGROUND: Optimal treatment strategies have not been identified for drug-eluting stent (DES) ISR. METHODS: Patients with a native coronary artery SES or PES ISR were randomized to SES or BA. In addition, a control group included BMS ISR treated with SES. Angiographic control was performed at 12 months. RESULTS: 281 patients were enrolled. Significant differences favoring SES over BA were noted in immediate and net gain (1.39 ± 0.51 vs. 0.97 ± 0.54 mm, P < 0.0001 and 1.07 ± 0.69 vs. 0.49 ± 0.67 mm, P < 0.0001), 12-month mean luminal diameter (MLD; 2.14 ± 0.62 vs. 1.71 ± 0.55 mm, P < 0.0001) and percent diameter stenosis (%DS; 21 ± 19.24 vs. 29.82 ± 18.47, P = 0.001). There was no significant difference at 12 months between SES and BA in the primary end-point late lumen loss (LLL; 0.37 ± 0.57 vs.0.41 ± 0.63, P = 0.73) and in in-stent binary restenosis (11.1% vs. 14%, P = 0.59). Target-lesion revascularization (TLR) was numerically lower in patients treated with SES (5.9% vs. 13.1%, P = 0.097). There was no difference according to the initial DES. In contrast, significantly higher immediate and net gains and MLD were noted in the BMS control group treated by SES. CONCLUSIONS: In this angiographic randomized trial comparing SES and BA in SES or PES restenosis, 12 month MLD, immediate and net gain, and %DS favored SES whereas no difference was noted in LLL. Condensed abstract optimal treatment strategies have not been identified for sirolimus-(SES) or paclitaxel-eluting stent (PES) in-stent restenosis (ISR). We randomized patients with a native coronary artery SES or PES ISR to SES or BA. In addition, a control group included BMS ISR treated with SES. There was no difference in the primary end-point, late lumen loss (LLL) at 12 months between the SES and BA groups. However, follow-up MLD and immediate and net gain favored SES.

Influence of age on the clinical outcomes of coronary revascularisation for the treatment of patients with multivessel de novo coronary artery lesions: sirolimus-eluting stent vs. coronary artery bypass surgery and bare metal stent, insight from the multicentre randomised Arterial Revascularisation Therapy Study Part I (ARTS-I) and Part II (ARTS-II).

AIMS: We sought to evaluate the prognostic impact of age on the procedural results and subsequent clinical outcomes in patients with multivessel disease (MVD) treated either by coronary artery bypass surgery (CABG) or by percutaneous coronary intervention (PCI) with or without drug eluting stents, based on data of the Arterial Revascularisation Therapies Study (ARTS) part I and part II. The potential influence of age in determining the most appropriate revascularisation strategy for patients with MVD is largely unknown. METHODS AND RESULTS: Three year clinical outcome of ARTS I patients randomised to PCI with bare metal stent (BMS) (n= 600) or CABG (n= 605), and matched patients treated by PCI with sirolimus-eluting stents (SES) in ARTS II (n= 607) were reviewed according to four age quartiles. Endpoints were measured in terms of major adverse cardiac and cerebrovascular events MACCE) during hospital stay and up to three years. The frequency of female, diabetes, hypertension, peripheral vascular disease, pulmonary disease, as well as lesion complexity increased with age. At three years, MACCE free survival was comparable between patients treated by CABG or SES PCI, regardless of age quartile. The incidence of MACCE was higher among ARTS I BMS treated patients in all but the second age quartile. This was primarily related to a higher need for repeat revascularisation among BMS treated patients. However, age, which emerged as a strong independent predictor of MACCE following CABG (p<0.005), was not predictive of adverse events following PCI. Conversely, diabetes was the strongest independent predictor of MACCE among PCI treated patients (p<0.02), but didn't affect three-year outcomes following CABG. CONCLUSIONS: Age seems to influence the CABG outcome in-hospital but not PCI. PCI-SES could offer lower immediate risk in patients with MVD and comparable long-term outcome as CABG especially in older patients. The worst outcome of PCI-BMS group is primarily related to the need for repeat revascularisation. Diabetes is the most important predictor of MACCE following PCI.

Short- and long-term health related quality-of-life and anginal status of the Arterial Revascularisation Therapies Study part II, ARTS-II; sirolimus-eluting stents for the treatment of patients with multivessel coronary artery disease.

AIMS: Assessment of health related quality-of-life (HRQL) has become increasingly important as not only the clinician's view of the technical success, but also the patient's perception is being measured. We evaluated the HRQL following sirolimus-eluting coronary stent (SES) (CYPHER(R); Cordis, Johnson & Johnson, Warren, NJ, USA) implantation in patients with multivessel disease, comparing the outcomes with the historical surgical and bare metal stent (BMS) arms of the ARTS-I study. METHODS AND RESULTS: The HRQL outcomes were compared to the outcome of the historical cohorts of the randomised ARTS-I trial using the same inclusion and exclusion criteria. HRQL was evaluated at baseline, at one month and at 6, 12 and 36 months after revascularisation using the SF-36 in patients treated with SES (n=585), BMS (n=483) or coronary artery bypass graft (CABG) (n=492). The HRQL compliance rates varied from 100% at baseline to 92% at 36 months. Both stenting and CABG resulted in significant improvement of HRQL and anginal status. There was a trend towards better HRQL after CABG than BMS beyond six months. Already from the first month up to three years, SES patients had, on average, 10% significantly better HRQL than BMS patients on the HRQL subscales physical functioning, role physical functioning, role emotional functioning and mental health (p<0.01) and a trend towards better HRQL in the other subscales. Up to 12 months, the HRQL was better after SES than CABG and was identical thereafter. At all time points, angina was more prevalent in the BMS group than in both the SES and CABG groups, in which the incidence of angina was similar. At three years, 10% of the SES patients suffered from angina, 13% of the CABG patients and 20% of the BMS patients. CONCLUSIONS: Both stenting and CABG resulted in a significant improvement in HRQL and angina. Along with a substantial reduction of restenosis, HRQL after SES was significantly improved as compared with BMS, and was similar to CABG.

5-year clinical outcomes of the ARTS II (Arterial Revascularization Therapies Study II) of the sirolimus-eluting stent in the treatment of patients with multivessel de novo coronary artery lesions.

OBJECTIVES: The purpose of this study is to compare the 5-year clinical outcomes, safety, and efficacy of sirolimus-eluting stents (SES) in the ARTS II (Arterial Revascularization Therapies Study II) with the outcomes of coronary artery bypass graft (CABG) and bare-metal stenting (BMS) from the ARTS I. BACKGROUND: The long-term outcomes after SES implantation in patients with multivessel disease remains to be established. METHODS: The ARTS I was a randomized trial of 1,205 patients with multivessel disease comparing CABG and BMS. The ARTS II study was a nonrandomized trial with the Cypher sirolimus-eluting stent (Cordis, a Johnson & Johnson Company, Warren, New Jersey), applying the same inclusion and exclusion criteria, end points, and protocol definitions. The ARTS II trial enrolled 607 patients, with an attempt to enroll at least one-third of patients with 3-vessel disease. RESULTS: At 5-year, the death/stroke/myocardial infarction event-free survival rate was 87.1% in ARTS II SES, versus 86.0% (p = 0.1) and 81.9% (p = 0.007) in ARTS I CABG and BMS cohorts, respectively. The 5-year major adverse cardiac and cerebrovascular event (MACCE) rate in ARTS II (27.5%) was significantly higher than ARTS I CABG (21.1%, p = 0.02), and lower than in ARTS I BMS (41.5%, p < 0.001). The cumulative incidence of definite stent thrombosis was 3.8%. Thirty-two percent (56 of 176) of major adverse cardiac events (MACE) at 5 years were related to possible, probable, or definite stent thrombosis. CONCLUSIONS: At 5 years, SES had a safety record comparable to CABG and superior to BMS, and a MACCE rate that was higher than in patients treated with CABG, and lower than in those treated with BMS. Approximately one-third of the events seen with SES could be prevented through the elimination of early, late, and very late stent thrombosis.

Three-year clinical outcome of percutaneous treatment of bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights from the Arterial Revascularisation Therapies Study, part II (ARTS II).

AIMS: The long-term impact of treating bifurcation lesions on the overall outcome of patients with multivessel coronary disease treated percutaneously with drug-eluting stents is unknown. This analysis determined the influence of bifurcation treatment using sirolimus-eluting stents on 3-year clinical outcomes. METHODS AND RESULTS: Of the 607 patients (2,160 lesions) in the ARTS II study, 324 patients underwent revascularisation procedures involving treatment of at least one bifurcation (465 lesions). Three-year outcomes were compared to those without bifurcations. Despite more diffuse and complex disease in the bifurcation group, survival free of adverse events was equivalent in the two groups. At 3-years, there was no difference in rate of overall MACCE (20.2% vs. 18.5%, p=NS) or any of the component events between the bifurcation and the non-bifurcation group. There was a trend for a higher rate of definite stent thrombosis in the bifurcation group (4.6 vs 2.1%, p=0.1), but in multivariate analysis the CK value post-procedure served as the only independent predictor of definite stent thrombosis (p=0.015), with the presence of a bifurcation lesion of borderline significance (p=0.056). CONCLUSIONS: In multivessel disease treated by PCI with DES, the presence of bifurcation disease had no adverse influence on 3-year clinical outcomes.

Multivessel coronary revascularization in patients with and without diabetes mellitus: 3-year follow-up of the ARTS-II (Arterial Revascularization Therapies Study-Part II) trial.

OBJECTIVES: The purpose of this study was to assess the 3-year outcome of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES) in patients who had multivessel coronary artery disease with and without diabetes mellitus. BACKGROUND: The optimal method of revascularization in diabetic patients remains in dispute. METHODS: The ARTS-II (Arterial Revascularization Therapies Study-Part II) trial is a single-arm study (n = 607) that included 159 diabetic patients treated with SES whose 3-year clinical outcome was compared with that of the historical diabetic and nondiabetic arms of the randomized ARTS-I trial (n = 1,205, including 96 diabetic patients in the CABG arm and 112 in the PCI arm). RESULTS: At 3 years, among nondiabetic patients, the incidence of the primary composite of death, CVA, myocardial infarction (MI), and repeat revascularization (major adverse cardiac and cerebrovascular events [MACCE]), was significantly lower in ARTS-II than in ARTS-I PCI (adjusted odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.26 to 0.64) and similar to ARTS-I CABG. The ARTS-II patients were at significantly lower risk for death, CVA, and MI as compared with both the ARTS-I PCI (adjusted OR: 0.55; 95% CI: 0.34 to 0.91) and ARTS-I CABG patients (adjusted OR: 0.56; 95% CI: 0.35 to 0.92). Among diabetic patients, the incidence of MACCE in ARTS-II was similar to that of both PCI and CABG in ARTS-I. Conversely, the incidence of death, CVA, and MI was significantly lower in ARTS-II than in ARTS-I PCI (adjusted OR: 0.67; 95% CI: 0.27 to 1.65) and was similar to that of ARTS-I CABG. CONCLUSIONS: At 3 years, PCI using SES for patients with multivessel coronary artery disease seems to be safer and more efficacious than PCI using bare-metal stents, irrespective of the diabetic status of the patient. Hence, PCI using SES appears to be a valuable alternative to CABG for both diabetic and nondiabetic patients.

Impact of body mass index on the one-year clinical outcome of patients undergoing multivessel revascularization with sirolimus-eluting stents (from the Arterial Revascularization Therapies Study Part II).

The differential safety and efficacy profiles of sirolimus-eluting stents when implanted in patients with multivessel coronary artery disease who have increased body mass indexes (BMIs) compared with those with normal BMIs are largely unknown. This study evaluated the impact of BMI on 1-year outcomes in patients with multivessel coronary artery disease treated with sirolimus-eluting stents as part of the Arterial Revascularization Therapies Study Part II (ARTS II). From February to November 2003, 607 patients were included at 45 centers; 176 patients had normal BMIs (<25 kg/m(2)), 289 were overweight (> or =25 and < or =30 kg/m(2)), and 142 were obese (>30 kg/m(2)). At 30 days, the cumulative incidence of the primary combined end point of death, myocardial infarction, cerebrovascular accident, and repeat revascularization (major adverse cardiac and cerebrovascular events) was 3.4% in the group with normal BMIs, 3.1% in overweight patients, and 2.8% in obese patients (p = 0.76). At 1 year, the cumulative incidence of major adverse cardiac and cerebrovascular events was 10.8%, 11.8%, and 7.0% in the normal BMI, overweight, and obese groups, respectively (p = 0.31). In conclusion, BMI had no impact on 1-year clinical outcomes in patients with multivessel coronary artery disease treated with sirolimus-eluting stents in ARTS II.

Three-year follow-up of the ARTS-II# - sirolimus-eluting stents for the treatment of patients with multivessel coronary artery disease.

AIMS: Late stent thrombosis has been documented in on- and off-label populations. Stent thrombosis is more frequently in higher risk patients and there is still scarce data about the impact on late adverse cardiac events. The aim therefore is to determine the 3-year safety and effectiveness of Sirolimus-Eluting Stent (SES) (Cypher(R)) implantation in patients with multivessel disease and to compare outcomes with the historical results of the two arms of the Arterial Revascularisation Therapies Study (ARTS-I). METHODS AND RESULTS: ARTS-II is a 45 centre, 607 patient single-arm study. Three years outcomes were compared to the outcome of the historical cohorts of ARTS-I using the same inclusion and exclusion criteria and major adverse cardiac and cerebrovascular events (MACCE) definitions. Patients were stratified by clinical site to ensure that at least 1/3 had 3-vessel disease to achieve a number of treated lesions per patient comparable to ARTS-I. Stent thrombosis was re-adjudicated using the ARC definitions. An angiographic coronary score to characterise lesion complexity was applied to allow the identification of patients who might benefit the most from multivessel stenting. In ARTS-II, 46.6% of the patients underwent 3-vessel treatment as compared to 18.0% in ARTS-I percutaneous coronary intervention (PCI) (n=600) with bare metal stents (BMS). Diabetes was present in 26.2% in ARTS-II as compared to 17.3% in ARTS-I. In ARTS-II, patients received on average 3.7 stents resulting in a mean total stented length of 72.5 mm. The 3-year survival rate in ARTS-II was 97.0%, comparable to the 95.6% and 96.0% of the historical surgical (n=605) and PCI cohorts of ARTS-I. The death/cerebrovascular accident (CVA)/myocardial infarction (MI) event free survival rate in ARTS-II was 91.7%, versus 89.1% (p=0.1) and 87.2% (p=0.007) in ARTS-I coronary artery bypass graft (CABG) and PCI cohorts, respectively. Freedom from revascularisation in ARTS-II was 85.5%, lower than in ARTS-I CABG (93.4%; p<0.001) but higher than in ARTS-I PCI (73.7%; p<0.001) cohorts. MACCE free survival was 80.6% in ARTS-II, comparable to ARTS-I CABG (83.8%; p=0.21) but superior to ARTS-I PCI (66.0%; p<0.0001). The incidence of stent thrombosis (ARC any) in ART-II was 6.4% (39/607 patients). CONCLUSIONS: Despite the higher clinical and angiographic risk profile, the overall MACCE rate at three years was lower in ARTS-II than in the ARTS-I PCI and comparable to ARTS-I CABG. However, the re-intervention rate in ARTS-I CABG remained significantly lower than in ARTS-II.

Cyphering the complexity of coronary artery disease using the syntax score to predict clinical outcome in patients with three-vessel lumen obstruction undergoing percutaneous coronary intervention.

The Syntax score (SXscore) was recently developed as a comprehensive angiographic scoring system aiming to assist in patient selection and risk stratification of patients with extensive coronary artery disease undergoing contemporary revascularization. A validation of this angiographic classification scheme is lacking. We assessed its predictive value in patients who underwent percutaneous intervention (PCI) for 3-vessel disease and explored its performance in comparison with the modified lesion classification system of the American Heart Association/American College of Cardiology. The SXscore, applied to 1,292 lesions in 306 patients who underwent PCI for 3-vessel disease in the Arterial Revascularization Therapies Study Part II, was 4 to 54.5, and after a median of 370 days (range 274 to 400) predicted the rate of major adverse cardiac and cerebrovascular events (hazard ratio 1.08/U increase, 95% confidence interval 1.05 to 1.11, p <0.0001), with patients in the highest SXscore tertile having a significantly higher event rate (27.9%) than patients in the lowest tertile (8.7%, hazard ratio 3.5, 95% confidence interval 1.7 to 7.4, p = 0.001). By multivariable analyses, SXscore independently predicted outcome with an almost fourfold adjusted increase in the risk of major adverse cardiac and cerebrovascular events in patients with high versus low values based on the discrimination level provided by classification and regression tree analysis. Compared with the modified lesion classification scheme of the American Heart Association/American College of Cardiology, SXscore showed a greater discrimination ability (c-index 0.58 +/- 0.08 vs 0.67 +/- 0.08, respectively, p <0.001) and a better goodness of fit with the Hosmer-Lemeshow statistic. In conclusion, the SXscore is a promising tool to risk stratify outcome in patients with extensive coronary artery disease undergoing contemporary PCI.

The clinical outcome of percutaneous treatment of bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights from the Arterial Revascularization Therapies Study part II (ARTS II).

AIMS: Little is known about the impact of treating bifurcations on the overall outcome of multivessel coronary artery disease treated with stenting. This analysis was made to investigate the 1 year clinical outcome of the treatment of bifurcation lesions using sirolimus-eluting stents (SES) in patients with multivessel disease. METHODS AND RESULTS: Among a total of 607 patients (2160 lesions) in the Arterial Revascularization Therapies Study part II (ARTS II), there were 324 patients in whom at least one bifurcation lesion was treated (465 lesions). Patients with bifurcations were compared with those without bifurcations in terms of baseline characteristics and major adverse cardiac and cerebrovascular events (MACCE). Patients with 'true' (200 patients) vs. 'partial' bifurcations (124 patients) and usage of a one- (263 patients) vs. two-stent strategy (61 patients) were also evaluated. The bifurcation group was associated with more complex lesion and procedural characteristics than the non-bifurcation group. However, there was no significant difference in 1 year MACCE rates between the bifurcation group and the non-bifurcation group (13.3 vs. 11.0%, P=0.46). MACCE in patients with true bifurcations was 13.0 vs. 13.7% for partial bifurcations (P=0.87) and 14.1 vs. 9.8% for one- vs. two-stent strategy (P=0.53). CONCLUSIONS: In this trial without angiographic follow-up, the presence of bifurcations did not affect 1 year outcomes after SES implantation. The outcomes in true vs. partial bifurcations and using one vs. two stents were similar when the treatment strategies were left to the operator's discretion.

Impact of stable versus unstable coronary artery disease on 1-year outcome in elective patients undergoing multivessel revascularization with sirolimus-eluting stents: a subanalysis of the ARTS II trial.

OBJECTIVES: We sought to evaluate the impact of unstable coronary artery disease (CAD) on short- and mid-term outcomes in patients with multivessel disease treated by multiple sirolimus-eluting stents (SES) as part of ARTS II (Arterial Revascularization Therapies Study Part II). BACKGROUND: The differential safety/efficacy profile of SES when implanted in patients with unstable angina (UA) in comparison with stable angina (SA) undergoing multivessel intervention is largely unknown. METHODS: Between February 2003 and November 2003, 607 patients at 45 participating centers were treated; 221 of them (36%) presented with UA. RESULTS: At 30 days, the cumulative rate of death, myocardial infarction-defined as any creatine kinase (CK)/CK-myocardial band elevation beyond the upper limit of normal-cerebrovascular accident, and repeat revascularization (i.e., major adverse cardiac and cerebrovascular events [MACCEs]) was 19.9% in both groups. Angiographic subacute stent occlusion was documented in 1 (0.5%) and 4 (1%) patients in the UA and SA groups, respectively. At 1 year, the cumulative incidence of MACCEs was 27.1% in the UA and 24.9% in the SA group (p = 0.56). Two late occlusions occurred, both in the SA group. After adjustment for baseline and procedural characteristics, the presence of UA was not identified as an independent predictor of MACCE (hazard ratio 0.94; 95% confidence interval 0.41 to 2.12; p = 0.88). These findings remained consistent after increasing the CK/CK-myocardial band threshold to define periprocedural myocardial infarction up to at least 3 or 5 times the upper limit of normal. CONCLUSIONS: In ARTS II, an unstable clinical presentation did not exert a negative impact on short- and mid-term outcome after SES implantation for multivessel disease. (ARTS II Trial; ; NCT00235170).

One-year results of coronary revascularization in diabetic patients with multivessel coronary artery disease.Sirolimus stent vs. coronary artery bypass surgery and bare metal stent: insights from ARTS-II and ARTS-I.

BACKGROUND: ARTS-II was designed to evaluate the sirolimus-eluting stent (SES) versus ARTS-I. The objective of this analysis is to assess the safety and efficacy of the SES in diabetic patients with multivessel disease (MVD) versus both arms of ARTS-I. METHODS AND RESULTS: The ARTS studies included 367 diabetic patients (ARTS-II: 159; ARTS-I-CABG: 96; ARTS-I-PCI: 112). Baseline characteristics showed a more diseased patient population in the ARTS-II study: 50.3% with 3VD vs. 35.4% (ARTS-I-CABG) and 30.8% (ARTS-I-PCI) (p=0.003). Treated or anastomosed lesions were 3.2+/-1.2 (ARTS-II), 2.8+/-0.8 (ARTS-I-CABG) and 2.5+/-1.1 (ARTS-I-PCI). At 30 days there was a significant difference in MACCE between ARTS-II (4.4%) and ARTS-I-PCI (12.5%) (p=0.02). At 1-year, the death rate was 2.5% (ARTS-II) vs. 3.1% (ARTS-I-CABG) and 6.3% (ARTS-I-PCI) without significant differences. Myocardial infarction rate was 0.6% (ARTS-II) vs. 2.1% (ARTS-I-CABG; p=0.56) and 6.3% (ARTS-I-PCI; p=0.01). The need for repeat revascularization was 12.6% (ARTS-II) vs. 4.2% (ARTS-I-CABG; p=0.027) and 22.3% (ARTS-I-PCI; p= 0.046). MACCE-free survival was 84.3% (ARTS-II) vs. 85.4% (ARTS-I-CABG; p=0.86) and 63.4% (ARTS-I-PCI; p<0.001). Also at 1 year, the overall MACCE rate in patients with diabetes was significantly higher than in nondiabetic patients, 15.7% vs. 8.5%, respectively [RR 1.85, 95%CI (1.16,2.97), p=0.015), due to a higher incidence of death and need for repeat revascularization, 2.5% vs. 0.4 and 12.5% vs. 5.6% in diabetes vs. nondiabetes groups, respectively. CONCLUSION: Despite more extensive and treated disease, the overall MACCE-free survival in diabetic patients at 1 year in ARTS-II is similar to ARTS-I-CABG.