Dick Goedhart

Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial

BACKGROUND Everolimus-eluting and paclitaxel-eluting stents, compared with bare metal stents, reduced the risk of restenosis in clinical trials with strict inclusion and exclusion criteria. We compared the safety and efficacy of the second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice. METHODS We randomly assigned 1800 consecutive patients (aged 18-85 years) undergoing percutaneous coronary intervention at one centre to treatment with everolimus-eluting or paclitaxel-eluting stents. The primary endpoint was a composite of safety and efficacy (all-cause mortality, myocardial infarction, and target vessel revascularisation) within 12 months. Patients were not told which stent they had been allocated. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01016041. FINDINGS Follow-up was completed in 1797 patients. The primary endpoint occurred in 56 (6%) of 897 patients in the everolimus-eluting stent group versus 82 (9%) of 903 in the paclitaxel-eluting stent group (relative risk 0.69 [95% CI 0.50-0.95], p value for superiority=0.02). The difference was attributable to a lower rate of stent thrombosis (6 [<1%] vs 23 [3%], 0.26 [0.11-0-64], p=0.002), myocardial infarction (25 [3%] vs 48 [5%], 0.52 [0.33-0.84], p=0.007), and target vessel revascularisation (21 [2%] vs 54 [6%], 0.39 [0.24-0.64], p=0.0001). Cardiac death, non-fatal myocardial infarction, or target lesion revascularisation occurred in 44 [5%] patients in the everolimus-eluting stent group versus 74 [8%] patients in the paclitaxel-eluting stent group, p value for superiority was 0.005. INTERPRETATION The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice. FUNDING Unrestricted grants from Abbott Vascular and Boston Scientific.

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.

The SYNTAX score revisited: A reassessment of the SYNTAX score reproducibility

Objectives: To reassess the reproducibility of the SYNTAX score. Background: The SYNTAX score appears to have an important role to play in the evaluation of patients with complex coronary artery disease undergoing revascularisation. However, the calculation of the SYNTAX score relies on the subjective assessment of lesions using coronary angiography, and therefore is subject to intra‐and inter‐observer variability. Methods: The SYNTAX score was calculated in 100 patients randomly selected from the SYNTAX trial, on two occasions 8 weeks apart, by a team made up of three interventional cardiologists. The weighted kappa values were compared with values obtained 1 year previously, when core lab analysts assessed the intra‐observer reproducibility amongst the same patient cohort. Results: The mean ± standard deviation difference in SYNTAX score was 2.1 ± 7.6. The respective weighted kappa values for the number of lesions, bifurcation lesions, ostial lesions, and total occlusions were 0.62, 0.36, 0.66, and 0.91 compared with 0.59, 0.41, 0.63, and 0.82 in the previous core lab assessment. The weighted kappa for the intra‐observer reproducibility of the SYNTAX score grouped into deciles was 0.54, and according to the terciles ≤22, >22–≤32, >32 was 0.51 both indicating a moderate level of agreement beyond the level of chance. In the previous assessment, the comparative kappa values were 0.45 and 0.53. Conclusions: The SYNTAX score has moderate intra‐observer reproducibility when assessed by a team of three interventional cardiologists, which is consistent with a prior evaluation performed by core lab analysts. The scoring of bifurcation lesions remains the main source of inconsistency.

Value of Age, Creatinine, and Ejection Fraction (ACEF Score) in Assessing Risk in Patients Undergoing Percutaneous Coronary Interventions in the ‘All-Comers' LEADERS Trial

Background—The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in patients undergoing elective coronary artery bypass surgery; however, its utility in “all-comer” patients undergoing percutaneous coronary intervention is yet unexplored. Methods and Results—The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEFlow ⩽1.0225, 1.0225< ACEFmid ⩽1.277, and ACEFhigh >1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event–free survival in the highest tertile of the ACEF score (ACEFlow=92.1%, ACEFmid=89.5%, and ACEFhigh=86.1%; P=0.0218). Cardiac death was less frequent in ACEFlow than in ACEFmid and ACEFhigh (0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEFhigh vs 5.2% for ACEFmid and 2.5% for ACEFlow; hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEFhigh group, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEFhigh group (ACEFlow=1.2%, ACEFmid=3.5%, and ACEFhigh=6.2%; hazard ratio=2.04, P<0.001). Conclusions—ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00389220.

The Impact of Body Mass Index on the One Year Outcomes of Patients Treated by Percutaneous Coronary Intervention With Biolimus- and Sirolimus-Eluting Stents (from the LEADERS Trial)

The aim of this analysis was to assess the effect of body mass index (BMI) on 1-year outcomes in patients enrolled in a contemporary percutaneous coronary intervention trial comparing a sirolimus-eluting stent with a durable polymer to a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients who underwent percutaneous coronary intervention were randomized to treatment with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n = 850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 1 year, the incidence of the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was assessed. In addition, rates of clinically justified target lesion revascularization and stent thrombosis were assessed. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 1-year mortality. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was significantly higher in the obese group (8.7% in normal-weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent predictor of stent thrombosis. Stent type had no impact on the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95% confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an independent predictor of major adverse cardiac events at 1-year clinical follow-up. The higher incidence of stent thrombosis in the obese group may suggest the need for a weight-adjusted dose of clopidogrel.

Everolimus-eluting stents and paclitaxel-eluting stents in patients presenting with myocardial infarction: insights from the two-year results of the COMPARE prospective randomised controlled trial.

AIMS Although large clinical trials have shown that everolimus-eluting stents (EES) significantly reduce target vessel revascularisation (TVR), myocardial infarction (MI) and stent thrombosis (ST) compared to paclitaxel-eluting stents (PES) in diverse populations, there is a paucity of data comparing EES and PES in patients presenting with MI. METHODS AND RESULTS We performed a post hoc subgroup analysis on COMPARE, an all-comer trial comparing EES to PES. We identified 863 patients (EES=434, PES=429 treated for MI: 452 ST-elevation MI (STEMI) and 411 non ST-elevation MI (NSTEMI). EES was associated with a significant reduction in the primary endpoint, a composite of all-cause mortality, MI, and TVR, at two years (RR=0.57; 95% CI: 0.40-0.83, p=0.002). While the effect was more marked in the STEMI (RR=0.51; 95% CI: 0.30-0.87, p=0.01) than the NSTEMI subgroup (RR=0.65; 95% CI: 0.39-1.08, p=0.09), the interaction p-value (0.5) suggests that a difference in treatment effect between presentations is unlikely. ST rates were significantly lower with EES (RR=0.30; 95% CI: 0.12-0.73, p=0.005). CONCLUSIONS At two years, EES results are superior to PES in terms of safety and efficacy endpoints in treatment of MI.

Morphology discrimination in implantable cardioverter-defibrillators: consistency of template match percentage during atrial tachyarrhythmias at different heart rates

BACKGROUND Morphology discrimination (MD) in implantable cardioverter-defibrillators (ICDs) is based on the comparison of the ventricular electrogram during tachycardia with a stored reference template obtained during baseline rhythm. However, the effect of heart rate on the template match percentage during supraventricular tachyarrhythmias (SVT) is not known. The purpose of this study was to evaluate the performance of the template match percentage during SVT at different heart rates. METHODS AND RESULTS Stored electrograms of 868 tachyarrhythmias from 88 patients with a dual-chamber ICD (St Jude Medical, USA) were analysed by the investigators. The effect of heart rate on template match percentage was estimated by regression analysis. For performance measures, data were corrected for multiple episodes in a patient by using the generalized estimating equation method. The mean template match percentage was 86.6 +/- 22.2% (median 100%) for SVT episodes. No significant differences in template match percentage between fast [ventricular cycle length (CL) 300-350 ms] and slow (ventricular CL >400 ms) SVTs were observed (85.4 +/- 27.0 vs. 87.1 +/- 19.7%). Using nominal settings, MD alone provided sensitivity and specificity of 70.2% and 89.4% overall, respectively. Morphology discrimination in conjunction with rate branch analysis, sudden onset, and stability yielded sensitivity and specificity of 98.5% and 91.2%, respectively. CONCLUSION Morphology discrimination has a consistently high template match percentage during SVTs, which is independent of ventricular CL. The consistent high match percentage results in high specificity for arrhythmia discrimination.

A comparison of the distribution of necrotic core in bifurcation and non-bifurcation coronary lesions: an in vivo assessment using intravascular ultrasound radiofrequency data analysis.

AIMS High-risk plaques are prone to develop at the site of coronary vessel bifurcations. The distribution of necrotic core at bifurcation lesions (BL) is known, however, little has been described on the necrotic core distribution in non-BLs. Therefore we compared the distribution of necrotic core between BL and non-BLs in coronary arteries using IVUS-VH imaging. METHODS AND RESULTS A total of 129 patients (112 non-BL and 108 BL) were included. The lesions were divided into upstream and downstream segments according the location of the minimum lumen area (MLA) within the plaque. In BLs, compositional analysis showed no differences between the three segments. The necrotic core in contact with the lumen that was located in the downstream segment was significantly larger. While in non-BLs, this was not significantly different between segments. Plaque burden in BLs was 56.60±5.79% vs. 55.50±4.54% in non-BLs, p=0.04. Mean necrotic core area was larger in BLs 0.84±0.55mm2 vs. 0.70±0.49mm2, p=0.048. Mean percentage necrotic core was 15.48±8.02% vs. 14.51±7.64%, p=0.37. There was a trend towards a greater content of necrotic core in contact with the lumen in BLs. The percentage of frames with a major confluent pool of necrotic core in contact with the lumen >10% in BLs was 11.78±17.18 vs. 8.95±17.86 in non-BLs, p=0.065. There was a statistically significant difference in the frequency of IVUS derived thin capped fibroatheromas between bifurcation lesions 20 vs. 13 in non-bifurcation lesions, p=0.03. CONCLUSIONS Bifurcation lesions appear to have a larger plaque burden with a different plaque composition compared to non-bifurcation lesions. This may partly explain the adverse outcomes seen following treatment of bifurcation lesions in contemporary practice.

Differential protein biomarker expression and their time-course in patients with a spectrum of stable and unstable coronary syndromes in the Integrated Biomarker and Imaging Study-1 (IBIS-1)

OBJECTIVES IBIS-1 was a pilot study undertaken to correlate coronary imaging with circulating biomarker expression in patients with stable angina, unstable angina and acute myocardial infarction. We hypothesized that patients at high risk of future events could be identified in the future by a combination of high risk plaque features by plaque echogenicity and palpography and a set of circulating blood biomarkers. RESULTS AND METHODS We assessed the expression of conventional biomarkers and novel marker protein microarray (170 analytes) over 6 months. There were no strong correlations observed between conventional biomarkers and coronary imaging in non-culprit artery. Proteomic microarray was performed in 66 patients. Seventy eight (45%) analytes showed dynamic changes over time. Using hierarchical clustering and principal component analysis two subsets of biomarkers were identified: initial up-regulation and decrease over time (D-dimer, hepatocyte growth factor, CXCL9/MIG, platelet factor 4/CXCL4, CTACK, C-6 Kine, follistatin, and FGF-7) and the opposite increase (PAI-1- anti-apoptotic protein and I-309--chemokine induced on the human endothelium by Lp(a)). CONCLUSIONS Proteomic analysis identifies dynamic patterns in circulating biomarkers in a wide range of patients with coronary artery disease. Further large natural history studies are needed to better define multibiomarker sets for identification of patients at risk of future CV events.

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.