Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: Final 5-year report of the LEADERS (limus eluted from a durable versus erodable stent coating) randomized, noninferiority trial
Serruys P.W.,Erasmus Medical Center |
Farooq V.,Erasmus Medical Center |
Kalesan B.,University of Bern |
De Vries T.,Cardialysis |
And 17 more authors.
JACC: Cardiovascular Interventions | Year: 2013
Objectives This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. Background The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. Methods The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. Results At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005). Conclusions The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220) © 2013 by the American College of Cardiology Foundation.
Serruys P.W.,Erasmus Medical Center |
Onuma Y.,Erasmus Medical Center |
Garg S.,Erasmus Medical Center |
Vranckx P.,Hartcentrum |
And 11 more authors.
Journal of the American College of Cardiology | Year: 2010
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. © 2010 American College of Cardiology Foundation.
Fox K.A.A.,University of Edinburgh |
Carruthers K.F.,University of Edinburgh |
Dunbar D.R.,University of Edinburgh |
Graham C.,University of Edinburgh |
And 5 more authors.
European Heart Journal | Year: 2010
AimTo define the long-term outcome of patients presenting with acute coronary syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to test the hypothesis that the GRACE (Global Registry of Acute Coronary Events) risk score predicts mortality and death/MI at 5 years.Methods and resultsIn the GRACE long-term study, UK and Belgian centres prospectively recruited and followed ACS patients for a median of 5 years (1797 days). Primary outcome events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke and re-hospitalization for ACS. There were 736 deaths, 19.8 (482 CVDs, 13) and 347 (9.3) MIs (>24 h), 261 strokes (7.7), and 452 (17) subsequent revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2 had >1 admission, 9.2 had 5+ admissions. These events were despite high rates of guideline indicated therapies. The GRACE score was highly predictive of all-cause death, CVD, and CVD/MI at 5 years (death: χ 2 likelihood ratio 632; Wald 709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P< 0.0001; CVD/MI C-statistic 0.70, P< 0.0001). Compared with the low-risk GRACE stratum (ESC Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95 CI 1.63, 2.81] and those with high-risk (HR 6.36, 95 CI 4.95, 8.16) had two- and six-fold higher risk of later death (Cox proportional hazard). A landmark analysis after 6 months confirmed that the GRACE score predicted long-term death (χ 2 likelihood ratio 265.4; Wald 289.5, P< 0.0001). Although in-hospital rates of death and MI are higher following STEMI, the cumulative rates of death (and CVD) were not different, by class of ACS, over the duration of follow-up (Wilcoxon = 1.5597, df = 1, P= 0.21). At 5 years after STEMI 269/1403 (19) died; after non-STEMI 262/1170 (22) after unstable angina (UA) 149/850 (17). Two-thirds (68) of STEMI deaths occurred after initial hospital discharge, but this was 86 for non-STEMI and 97 for UA.ConclusionThe GRACE risk score predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI. Their morbidity burden is high (MI, stroke, readmissions) and the substantial late mortality in non-STE ACS is under-recognized. The findings highlight the importance of pursuing novel approaches to diminish long-term risk. © 2010 The Author.
Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial
Stefanini G.G.,University of Bern |
Kalesan B.,University of Bern |
Serruys P.W.,Erasmus University Rotterdam |
Heg D.,University of Bern |
And 16 more authors.
The Lancet | Year: 2011
Background: The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7) patients versus 192 (22·6) patients (rate ratios [RR] 0·81, 95 CI 0·66-1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35-1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95 CI 0·06-0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51-1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (p interaction=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41-1·80) during the first year and 0·17 (0·04-0·78) during subsequent years (p interaction=0·049). Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Biosensors Europe SA, Switzerland. © 2011 Elsevier Ltd.
Jimenez-Perez J.,Hospital Of Navarra |
Casellas J.,Hospital General Universitario Of Alicante |
Garcia-Cano J.,Hospital Virgen Of La Luz |
Vandervoort J.,Onze Lieve Vrouw Ziekenhuis |
And 7 more authors.
American Journal of Gastroenterology | Year: 2011
Objectives: To date, this is the largest prospective series in patients with malignant colorectal obstruction to evaluate the effectiveness and safety of colonic self-expanding metal stents (SEMSs) as an alternative to emergency surgery. SEMSs allow restoration of bowel transit and careful tumor staging in preparation for elective surgery, hence avoiding the high morbidity and mortality associated with emergency surgery and stoma creation. Methods: This report is on the SEMS bridge-to-surgery subset enrolled in two multicenter international registries. Patients were treated per standard of practice, with documentation of clinical and procedural success, safety, and surgical outcomes. Results: A total of 182 patients were enrolled with obstructive tumor in the left colon (85%), rectum (11%), or splenic flexure (4%). Of these patients, 86% had localized colorectal cancer without metastasis. Procedural success was 98% (177/181). Clinical success was 94% (141/150). Elective surgery was performed in 150 patients (9 stomas) and emergency surgery in 7 patients for treatment of a complication (3 stomas). The overall complication rate was 7.8% (13/167), including perforation in 3% (5/167), stent migration in 1.2% (2/167), bleeding in 0.6% (1/167), persistent colonic obstruction in 1.8% (3/167), and stent occlusion due to fecal impaction in 1.2% (2/167). One patient died from complications related to surgical management of a perforation. Conclusions: SEMSs provide an effective bridge to surgery treatment with an acceptable complication rate in patients with acute malignant colonic obstruction, restoring luminal patency and allowing elective surgery with primary anastomosis in most patients. © 2011 by the American College of Gastroenterology.
Schepens T.,University of Antwerp |
Cammu G.,Onze Lieve Vrouw Ziekenhuis
Acta Anaesthesiologica Belgica | Year: 2014
Non-depolarizing neuromuscular blocking agents (NMBAs) produce neuromuscular blockade by competing with acetylcholine at the neuromuscular junction, whereas depolarizing NMBAs open receptor channels in a manner similar to that of acetylcholine. Problems with NMBAs include malignant hyperthermia caused by succinylcholine, anaphylaxis with the highest incidence for succinylcholine and rocuronium, and residual neuromuscular blockade. To reverse these blocks, anticholinesterases can act indirectly by increasing the amount of acetylcholine in the neuromuscular junction; sugammadex is the only selective relaxant binding agent (SRBA) in clinical use. At all levels of blockade, recovery after sugammadex is faster than after neostigmine. Sugammadex potentially also has some other advantages over neostigmine that are related to neostigmine's increase in the amount of acetylcholine and the necessity of co-administering anticholinergics. However, hypersensitivity reactions, including anaphylaxis, have occurred in some patients and healthy volunteers after sugammadex and remain an issue for the FDA. In the near future, we may see the emergence of new SRBAs and of easier-to-use technologies that can routinely monitor neuromuscular transmissions in daily practice. The nature of the effect of sugammadex on freeing nicotinic acetylcholine receptors located outside the neuromuscular junction from NMBAs is unknown. Moreover, it is uncertain whether the full removal of the competing antagonists (by SRBAs) at the neuromuscular junction impacts the efficiency of acetylcholine transmission. In a recent pilot study in healthy volunteers, we demonstrated increased electromyographic diaphragm activity after sugammadex, compared to neostigmine. Further research is needed to elucidate the role of NMBAs and their reversal agents in the central control of breathing, respiratory muscle activity, and respiratory outcomes. © 2014 Acta Anæsthesiologica Belgica.
Cammu G.,Onze Lieve Vrouw Ziekenhuis |
Van Vlem B.,Renal Unit |
Van Den Heuvel M.,Clinical PKPD |
Stet L.,CNS Global Clinical Trial Management |
And 3 more authors.
British Journal of Anaesthesia | Year: 2012
Background. Renal excretion is the primary route for the elimination of sugammadex. We evaluated the dialysability of sugammadex and the sugammadexrocuronium complex in patients with severe renal impairment in the intensive care unit (ICU). Methods. Six patients in the ICU with acute severe renal impairment received general anaesthesia for transoesophageal echocardiography, to replace their tracheal tubes, or for bronchoscopy. Five of the six patients were in the ICU after cardiac/vascular surgery and one for pneumonia-induced respiratory failure. They all received rocuronium 0.6 mg kg -1, followed 15 min later by sugammadex 4.0 mg kg -1. Two patients were studied for two dialysis episodes and four patients for four episodes. Rocuronium and sugammadex concentrations were measured in plasma and dialysate at several time points before, during, and after high-flux dialysis. Dialysis clearance in plasma and dialysate, and reduction ratio (RR) (the extent of the plasma concentration reduction at the end of a dialysis episode when compared with before dialysis) were calculated for each dialysis episode. Results. Dialysis episodes lasted on average 6 h. Observed RRs indicated mean reductions of 69% and 75% in the plasma concentrations of sugammadex and rocuronium, respectively, during the first dialysis episode. Reductions were around 50% during sequential dialysis episodes. On average, dialysis clearance of sugammadex and rocuronium in blood was 78 and 89 ml min -1, respectively. Conclusions. Haemodialysis using a high-flux dialysis method is effective in removing sugammadex and the sugammadexrocuronium complex in patients with severe renal impairment. © 2012 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
A prospective, observational study comparing postoperative residual curarisation and early adverse respiratory events in patients reversed with neostigmine or sugammadex or after apparent spontaneous recovery
Camu G.V.,Onze Lieve Vrouw Ziekenhuis |
Smet V.,Onze Lieve Vrouw Ziekenhuis |
De Jongh K.,Onze Lieve Vrouw Ziekenhuis |
Vandeput D.,Onze Lieve Vrouw Ziekenhuis
Anaesthesia and Intensive Care | Year: 2012
Six years ago, a study performed in our department reported that the incidence of postoperative residual curarisation (PORC) was 39%. The reassessment of neuromuscular monitoring and reversal of neuromuscular block in routine anaesthetic practice is relevant now that sugammadex has become available. The incidence of PORC, defined by a train-of-four (TOF) <90%, was evaluated at post-anaesthesia care unit (PACU) arrival in patients whose neuromuscular block had been reversed with neostigmine or sugammadex and those in whom reversal was felt unnecessary (adequate spontaneous recovery). During the PACU stay we recorded the oxygen saturation (SpO2) at arrival, episodes of SpO2 <90%, airway manoeuvres and/or stimulation required to maintain SpO2 >90%, and the need for re-intubation. In total, 624 patients were studied. Fifteen percent (66/441) of the patients who were not reversed, 15% (21/139) of those who were reversed with neostigmine and 2% (1/44) of those who received sugammadex exhibited PORC (P=0.06). No patient required reintubation in the PACU. The absence of neuromuscular monitoring and pharmacological reversal before extubation were not associated with PORC. A TOF <90% at PACU arrival was not associated with SpO2 <90% during the PACU stay. Body mass index was the only independent predictor of SpO 2 <90% during the stay in the PACU. These findings indicate that in recent years, the incidence of PORC, defined by a TOF <90%, has dramatically decreased in our institution. The differences in PORC were not statistically significant between patients who received sugammadex for reversal and patients with spontaneous recovery or neostigmine reversal.
Van Gestel L.,Catholic University of Leuven |
Cammu G.,Onze Lieve Vrouw Ziekenhuis
Acta Anaesthesiologica Belgica | Year: 2013
The aim of this literature review was to compare the duration of the recovery effects of sugammadex. We therefore systematically searched Medline for relevant reports that investigated the recovery time to a train-of-four (TOF) ratio of 0.9 after sugammadex administration. Thirty-three reports were retrieved. For the recommended dose of 2 mg/kg of sugammadex, some studies noted maximum reversal times to a TOF ratio of 0.9 of up to 12 minutes. One study recorded a maximum delay of 22.3 minutes after the recommended dose of 4 mg/kg of sugammadex. Regarding the reversal of rocuronium immediately after its administration, a maximum delay of 16.6 minutes was noted after 16 mg/kg of sugammadex. Whereas reversal with sugammadex is likely within 2-3 minutes, unexpectedly long sugammadex recovery times were occasionally recognized in elderly patients, patients with slower hemodynamic circulation, patients with pulmonary disease, some obese patients, and some cases of renal failure. Additionally, variability in the onset of sugammadex effect was observed in healthier patients (up to 22.3 minutes). This review confirms the known rapid reversal by the recommended doses of sugammadex. However, due to possibility of an increased recovery time, any patient who receives sugammadex to reverse neuromuscular block should have his or her TOF checked prior to extubation. © Acta Anæsthesiologica Belgica, 2013.
Cammu G.,Onze Lieve Vrouw Ziekenhuis |
Coart D.,Onze Lieve Vrouw Ziekenhuis |
De Graeve K.,Onze Lieve Vrouw Ziekenhuis |
Beelen R.,Onze Lieve Vrouw Ziekenhuis
Acta Anaesthesiologica Belgica | Year: 2012
The aim of this study was to assess the hemodynamic stability and efficacy of 2 mg/kg sugammadex in reversing rocuronium-induced neuromuscular block in patients with heart failure. Twelve patients who had an ejection fraction ≤ 25% and who were undergoing general anesthesia for cardiac resynchronization therapy, an automated implantable cardioverter-defibrillator, or battery replacement of the device were included. Neuromuscular function was monitored by acceleromyography of the adductor pollicis muscle. Each patient received 0.6 mg/kg of rocuronium and maintenance doses of 0.1 mg/kg when required. When the second twitch appeared at the end of surgery, the patients received 2 mg/kg sugammadex. After the administration of sugammadex, the time for recovery to a normalized train-of-four (TOF) ratio of 0.9 was 2.78 ± 0.67 min. Blood pressure and heart rate remained stable up to 10 min after the administration of sugammadex and then increased by the 30-min assessment. Three patients had episodes of SpO2 < 90% in the postanesthesia care unit. No sugammadex-related adverse events were reported. Sugammadex can adequately restore neuromuscular function in heart failure patients under hemodynamically stable conditions. However, longer reversal times are required than previously observed in healthy, young patients. © Acta Anœsthesiologica Belgica, 2012.