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Background The choice of optimal drug-eluting stent therapy for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention remains uncertain. We aimed to assess the long-term clinical outcomes after percutaneous coronary intervention with biodegradable polymer sirolimus-eluting stents (BP-SES) versus durable polymer everolimus-eluting stents (DP-EES) in patients with DM. Methods and Results In a prespecified subgroup analysis of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization) trial (NCT01443104), patients randomly assigned to ultrathin-strut BP-SES or thin-strut DP-EES were stratified according to diabetic status. The primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization, at 5 years. Among 2119 patients, 486 (22.9%) presented with DM. Compared with individuals without DM, patients with DM were older and had a greater baseline cardiac risk profile. In patients with DM, target lesion failure at 5 years occurred in 74 patients (cumulative incidence, 31.0%) treated with BP-SES and 57 patients (25.8%) treated with DP-EES (risk ratio, 1.23; 95% CI, 0.87-1.73 [ P =0.24]). In individuals without DM, target lesion failure at 5 years occurred in 124 patients (16.8%) treated with BP-SES and 132 patients (16.8%) treated with DP-EES (risk ratio, 0.98; 95% CI, 0.77-1.26 [ P =0.90; P for interaction=0.31]). Cumulative 5-year incidence rates of cardiac death, target vessel myocardial infarction, clinically indicated target lesion revascularization, and definite stent thrombosis were similar among patients with DM treated with BP-SES or DP-EES. There was no interaction between diabetic status and treatment effect of BP-SES versus DP-EES. Conclusions In a prespecified subgroup analysis of the BIOSCIENCE trial, we found no difference in clinical outcomes throughout 5 years between patients with DM treated with ultrathin-strut BP-SES or thin-strut DP-EES. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01443104.

Background: Newer-generation drug-eluting stents that combine ultrathin strut metallic platforms with biodegradable polymers might facilitate vascular healing and improve clinical outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI) compared with contemporary thin strut second-generation drug-eluting stents. We did a randomised clinical trial to investigate the safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stents versus thin strut durable polymer everolimus-eluting stents in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI., Methods: The BIOSTEMI trial was an investigator-initiated, multicentre, prospective, single-blind, randomised superiority trial at ten hospitals in Switzerland. Patients aged 18 years or older with acute STEMI who were referred for primary PCI were eligible to participate. Patients were randomly allocated (1:1) to either biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Central randomisation was done based on a computer-generated allocation sequence with variable block sizes of 2, 4, and 6, which was stratified by centre, diabetes status, and presence or absence of multivessel coronary artery disease, and concealed using a secure web-based system. Patients and treating physicians were aware of group allocations, whereas outcome assessors were masked to the allocated stent. The experimental stent (Orsiro; Biotronik; Bülach, Switzerland) consisted of an ultrathin strut cobalt-chromium metallic stent platform releasing sirolimus from a biodegradable polymer. The control stent (Xience Xpedition/Alpine; Abbott Vascular, Abbott Park, IL, USA) consisted of a thin strut cobalt-chromium stent platform that releases everolimus from a durable polymer. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial reinfarction (Q-wave and non-Q-wave), and clinically-indicated target lesion revascularisation, within 12 months of the index procedure. All analyses were done with the individual participant as the unit of analysis and according to the intention-to-treat principle. The trial was registered with ClinicalTrials.gov, number NCT02579031., Findings: Between April 26, 2016, and March 9, 2018, we randomly assigned 1300 patients (1623 lesions) with acute myocardial infarction to treatment with biodegradable polymer sirolimus-eluting stents (649 patients and 816 lesions) or durable polymer everolimus-eluting stents (651 patients and 806 lesions). At 12 months, follow-up data were available for 614 (95%) patients treated with biodegradable polymer sirolimus-eluting stents and 626 (96%) patients treated with durable polymer everolimus-eluting stents. The primary composite endpoint of target lesion failure occurred in 25 (4%) of 649 patients treated with biodegradable polymer sirolimus-eluting stents and 36 (6%) of 651 patients treated with durable polymer everolimus-eluting stents (difference -1·6 percentage points; rate ratio 0·59, 95% Bayesian credibility interval 0·37-0·94; posterior probability of superiority 0·986). Cardiac death, target vessel myocardial reinfarction, clinically-indicated target lesion revascularisation, and definite stent thrombosis were similar between the two treatment groups in the 12 months of follow-up., Interpretation: In patients with acute STEMI undergoing primary PCI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 1 year. This difference was driven by reduced ischaemia-driven target lesion revascularisation in patients treated with biodegradable polymer sirolimus-eluting stents compared with durable polymer everolimus-eluting stents., Funding: Biotronik., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Randomized trials evaluating the Orsiro biodegradable polymer sirolimus-eluting stent (BP-SES; 60 and 80 μm strut thickness for stent diameters ≤3 and >3 mm, respectively) did not stratify according to vessel size and failed to specify the impact of ultrathin-strut thickness on long-term clinical outcomes compared with durable polymer everolimus-eluting stents (DP-EES). We sought to assess the long-term effect of ultrathin-strut (60 μm) BP-SES versus thin-strut (81 μm) DP-EES on long-term outcomes in patients undergoing percutaneous coronary revascularization for small vessel disease., Methods: In a subgroup analysis of the randomized, multicenter, noninferiority BIOSCIENCE trial, patients with stable coronary artery disease or acute coronary syndrome randomly assigned to treatment with BP-SES or DP-EES were stratified according to vessel size (≤3 mm versus >3 mm) as a surrogate to compare patients treated with ultrathin-strut versus thin-strut drug-eluting stent. The primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization, within 5 years., Results: Among 2109 patients, 1234 (59%) were treated for small vessel disease. At 5 years, target lesion failure occurred in 124 patients (cumulative incidence, 22.3%) treated with ultrathin-strut BP-SES and 109 patients (18.3%) treated with thin-strut DP-EES (rate ratio, 1.22; 95% CI, 0.94-1.58; P =0.13). Cumulative incidences of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization and definite stent thrombosis at 5 years were similar in patients treated with ultrathin-strut BP-SES and thin-strut DP-EES. After adjustment for potential confounders, there was no significant interaction between vessel size and treatment effect of BP-SES versus DP-EES., Conclusions: We found no significant difference in clinical outcomes throughout 5 years between patients with small vessel disease treated with ultrathin-strut BP-SES versus thin-strut DP-EES., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104.

Background: Drug-eluting stents combining an ultrathin cobalt-chromium stent platform with a biodegradable polymer eluting sirolimus have been shown to be non-inferior or superior to thin-strut, durable-polymer, everolimus-eluting stents in terms of 1 year safety and efficacy outcomes., Methods: In the randomised, single-blind, multicentre, non-inferiority BIOSCIENCE trial, we compared biodegradable-polymer sirolimus-eluting stents with durable-polymer everolimus-eluting stents in patients with chronic stable coronary artery disease or acute coronary syndromes. Here, we assess the final 5-year clinical outcomes of BIOSCIENCE with regards to the primary clinical outcome of target lesion failure, which was a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation. The primary analysis was done by intention to treat. The BIOSCIENCE trial is registered with ClinicalTrials.gov, number NCT01443104., Findings: 2008 (95%) of 2119 patients recruited between March 1, 2012, and May 31, 2013, completed 5 years of follow-up. Target lesion failure occurred in 198 patients (cumulative incidence 20·2%) treated with biodegradable-polymer sirolimus-eluting stents and in 189 patients (18·8%) treated with durable-polymer everolimus-eluting stents (rate ratio [RR] 1·07, 95% CI 0·88-1·31; p=0·487). All-cause mortality was significantly higher in patients treated with biodegradable-polymer sirolimus-eluting stents than in those treated with durable-polymer everolimus-eluting stents (14·1% vs 10·3%; RR 1·36, 95% CI 1·06-1·75; p=0·017), driven by a difference in non-cardiovascular deaths. We observed no difference between groups in cumulative incidence of definite stent thrombosis at 5 years (1·6% in both groups; 1·02, 0·51-2·05; p=0·950)., Interpretation: 5-year risk of target lesion failure among all-comer patients undergoing percutaneous coronary intervention is similar after implantation of ultrathin-strut, biodegradable-polymer, sirolimus-eluting stents or thin-strut, durable-polymer, everolimus-eluting stents. Higher incidences of all-cause and non-cardiovascular mortality in patients treated with biodegradable-polymer stents eluting sirolimus than in those treated with durable-polymer stents eluting everolimus warrant careful observation in ongoing clinical trials., Funding: Clinical Trials Unit of the University of Bern and Biotronik., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: Our aim was to compare the safety and efficacy of a novel, ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) with a thin strut, durable polymer everolimus-eluting stent (DP-EES) in a pre-specified subgroup of patients with acute ST-segment elevation myocardial infarction (STEMI) enrolled in the BIOSCIENCE trial., Methods and Results: The BIOSCIENCE trial is an investigator-initiated, single-blind, multicentre, randomised non-inferiority trial (NCT01443104). Randomisation was stratified according to the presence or absence of STEMI. The primary endpoint, target lesion failure (TLF), is a composite of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularisation within 12 months. Between February 2012 and May 2013, 407 STEMI patients were randomly assigned to treatment with BP-SES or DP-EES. At one year, TLF occurred in seven (3.4%) patients treated with BP-SES and 17 (8.8%) patients treated with DP-EES (RR 0.38, 95% CI: 0.16-0.91, p=0.024). Rates of cardiac death were 1.5% in the BP-SES group and 4.7% in the DP-EES group (RR 0.31, 95% CI: 0.08-1.14, p=0.062); rates of target vessel myocardial infarction were 0.5% and 2.6% (RR 0.18, 95% CI: 0.02-1.57, p=0.082), respectively, and rates of clinically indicated target lesion revascularisation were 1.5% in the BP-SES group versus 2.1% in the DP-EES group (RR 0.69, 95% CI: 0.16-3.10, p=0.631). There was no difference in the risk of definite stent thrombosis., Conclusions: In this pre-specified subgroup analysis, BP-SES was associated with a lower rate of target lesion failure at one year compared to DP-EES in STEMI patients. These findings require confirmation in a dedicated STEMI trial.

Aims: The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes., Methods and Results: Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates., Conclusions: The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Aims: We sought to assess the performance of drug-eluting stents combining an ultrathin cobalt-chromium platform with a biodegradable polymer across categories of increasing SYNTAX score (SS)., Methods and Results: Patients included in the BIOSCIENCE trial and randomly allocated to treatment with biodegradable polymer sirolimus-eluting stents (BP-SES) or durable polymer everolimus-eluting stents (DP-EES) were categorised according to SS tertiles (low <8, medium 8-15, high >15). The primary endpoint, target lesion failure (TLF), was defined as a composite of cardiac death, target vessel myocardial infarction and clinically indicated target lesion revascularisation. The patient-oriented endpoint (POCE) included death, myocardial infarction, or any repeat revascularisation. The SS was available in 2,041 out of 2,119 patients (96.3%). At two-year follow-up, patients with an SS >15 experienced higher rates of both TLF and POCE as compared to patients with medium and low SS (14.5% vs. 8.1% and vs. 5.9%, p<0.001; 22.7% vs. 14.9% and vs. 12.4%; p<0.001), respectively. Comparable rates of the composite endpoints were documented for both stent types in each category of SS., Conclusions: Increasing lesion complexity as assessed by SS was associated with higher rates of TLF and POCE in a contemporary PCI population with minimal exclusion criteria. BP-SES and DP-EES showed comparable performance across the entire spectrum of CAD severity.

Background: Historically, percutaneous coronary intervention (PCI) of bifurcation lesions was associated with worse procedural and clinical outcomes when compared with PCI of non-bifurcation lesions. Newer generation drug-eluting stents (DES) might improve long-term clinical outcomes after bifurcation PCI., Methods and Results: The LEADERS trial was a 10-center, assessor-blind, non-inferiority, all-comers trial, randomizing 1,707 patients to treatment with a biolimus A9(TM) -eluting stent (BES) with an abluminal biodegradable polymer or a sirolimus-eluting stent (SES) with a durable polymer (ClinicalTrials.gov Identifier: NCT00389220). Five-year clinical outcomes were compared between patients with and without bifurcation lesions and between BES and SES in the bifurcation lesion subgroup. There were 497 (29%) patients with at least 1 bifurcation lesion (BES = 258; SES = 239). At 5-year follow-up, the composite endpoint of cardiac death, myocardial infarction (MI) and clinically-indicated (CI) target vessel revascularization (TVR) was observed more frequently in the bifurcation group (26.6% vs. 22.4%, P = 0.049). Within the bifurcation lesion subgroup, no differences were observed in (cardiac) death or MI rates between BES and SES. However, CI target lesion revascularization (TLR) (10.1% vs. 15.9%, P = 0.0495), and CI TVR (12.0% vs. 19.2%, P = 0.023) rates were significantly lower in the BES group. Definite/probable stent thrombosis (ST) rate was numerically lower in the BES group (3.1% vs. 5.9%, P = 0.15). Very late (>1 year) definite/probable ST rates trended to be lower with BES (0.4% vs. 3.1%, P = 0.057)., Conclusions: In the treatment of bifurcation lesions, use of BES led to superior long-term efficacy compared with SES. Safety outcomes were comparable between BES and SES, with an observed trend toward a lower rate of very late definite/probable ST between 1 and 5 years with the BES. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: No data are available on the long-term performance of ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES). We reported 2-year clinical outcomes of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation) trial, which compared BP-SES with durable-polymer everolimus-eluting stents (DP-EES) in patients undergoing percutaneous coronary intervention., Methods and Results: A total of 2119 patients with minimal exclusion criteria were assigned to treatment with BP-SES (n=1063) or DP-EES (n=1056). Follow-up at 2 years was available for 2048 patients (97%). The primary end point was target-lesion failure, a composite of cardiac death, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. At 2 years, target-lesion failure occurred in 107 patients (10.5%) in the BP-SES arm and 107 patients (10.4%) in the DP-EES arm (risk ratio [RR] 1.00, 95% CI 0.77-1.31, P=0.979). There were no significant differences between BP-SES and DP-EES with respect to cardiac death (RR 1.01, 95% CI 0.62-1.63, P=0.984), target-vessel myocardial infarction (RR 0.91, 95% CI 0.60-1.39, P=0.669), target-lesion revascularization (RR 1.17, 95% CI 0.81-1.71, P=0.403), and definite stent thrombosis (RR 1.38, 95% CI 0.56-3.44, P=0.485). There were 2 cases (0.2%) of definite very late stent thrombosis in the BP-SES arm and 4 cases (0.4%) in the DP-EES arm (P=0.423). In the prespecified subgroup of patients with ST-segment elevation myocardial infarction, BP-SES was associated with a lower risk of target-lesion failure compared with DP-EES (RR 0.48, 95% CI 0.23-0.99, P=0.043, Pinteraction=0.026)., Conclusions: Comparable safety and efficacy profiles of BP-SES and DP-EES were maintained throughout 2 years of follow-up., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: Arterial plaque rupture and thrombus characterise ST-elevation myocardial infarction (STEMI) and may aggravate delayed arterial healing following durable polymer drug-eluting stent (DP-DES) implantation. Biodegradable polymer (BP) may improve biocompatibility. We compared long-term outcomes in STEMI patients receiving BP-DES vs. durable polymer sirolimus-eluting stents (DP-SES)., Methods and Results: We pooled individual patient-level data from three randomised clinical trials (ISAR-TEST-3, ISAR-TEST-4 and LEADERS) comparing outcomes from BP-DES with DP-SES at four years. The primary endpoint (MACE) comprised cardiac death, MI, or target lesion revascularisation (TLR). Secondary endpoints were TLR, cardiac death or MI, and definite or probable stent thrombosis. Of 497 patients with STEMI, 291 received BP-DES and 206 DP-SES. At four years, MACE was significantly reduced following treatment with BP-DES (hazard ratio [HR] 0.59, 95% CI: 0.39-0.90; p=0.01) driven by reduced TLR (HR 0.54, 95% CI: 0.30-0.98; p=0.04). Trends towards reduction were seen for cardiac death or MI (HR 0.63, 95% CI: 0.37-1.05; p=0.07) and definite or probable stent thrombosis (3.6% vs. 7.1%; HR 0.49, 95% CI: 0.22-1.11; p=0.09)., Conclusions: In STEMI, BP-DES demonstrated superior clinical outcomes to DP-SES at four years. Trends towards reduced cardiac death or myocardial infarction and reduced stent thrombosis require corroboration in specifically powered trials.

Background: Although new-generation drug-eluting stents represent the standard of care among patients undergoing percutaneous coronary intervention, there remains debate about differences in efficacy and the risk of stent thrombosis between the Resolute zotarolimus-eluting stent (R-ZES) and the everolimus-eluting stent (EES). The aim of this study was to evaluate the safety and efficacy of the R-ZES compared with EES in patients undergoing percutaneous coronary intervention., Methods and Results: A systematic literature search of electronic resources was performed using specific search terms until September 2014. Random-effects meta-analysis was performed comparing clinical outcomes between patients treated with R-ZES and EES up to maximum available follow-up. The primary efficacy end point was target-vessel revascularization. The primary safety end point was definite or probable stent thrombosis. Secondary safety end points were cardiac death and target-vessel myocardial infarction. Five trials were identified, including a total of 9899 patients. Compared with EES, R-ZES had similar risks of target-vessel revascularization (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.90-1.24; P=0.50), definite or probable stent thrombosis (RR, 1.26; 95% CI, 0.86-1.85; P=0.24), cardiac death (RR, 1.01; 95% CI, 0.79-1.30; P=0.91), and target-vessel myocardial infarction (RR, 1.10; 95% CI, 0.89-1.36; P=0.39). Moreover, R-ZES and EES had similar risks of late definite or probable very late stent thrombosis (RR, 1.06; 95% CI, 0.53-2.11; P=0.87). No evidence of significant heterogeneity was observed across trials., Conclusions: R-ZES and EES provide similar safety and efficacy among patients undergoing percutaneous coronary intervention., (© 2015 American Heart Association, Inc.)

Aims: Stents with a passive coating of titanium-nitride-oxide (TiNO) have been compared with Endeavor® zotarolimus-eluting stents (E-ZES) with regard to the primary endpoint of in-stent late lumen loss at six to eight months. The objective of the present analysis was to compare the long-term outcomes of TiNO stents with E-ZES up to five years of clinical follow-up., Methods and Results: A total of 302 patients had been randomly allocated to treatment with TiNO or E-ZES. Up to five years of follow-up, major adverse cardiac events (MACE), the composite of cardiac death, myocardial infarction, or clinically indicated target vessel revascularisation (TLR), were observed in 27.6% of patients treated with TiNO stents and 25.3% of patients treated with E-ZES (RR 1.13, 95% CI: 0.72-1.75, p=0.60), with the majority of events related to clinically indicated TVR (TiNO 21.7% versus E-ZES 20.7%, RR 1.10, 95% CI: 0.67-1.81). There were no differences with respect to individual events including cardiac death, myocardial infarction or stent thrombosis between the two treatment arms up to five years of follow-up. A majority of patients remained free from angina throughout the entire study duration (TiNO 77.3% versus E-ZES 76.1%, p=0.92)., Conclusions: Final five-year outcomes of the TIDE trial comparing TiNO stents with E-ZES revealed increased rates of MACE driven primarily by clinically indicated TVR. The TIDE trial is registered at ClinicalTrials.gov: NCT00492908.

Background: Biodegradable polymers for release of antiproliferative drugs from drug-eluting stents aim to improve vascular healing. We assessed noninferiority of a novel ultrathin strut drug-eluting stent releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) compared with the durable polymer Xience Prime everolimus-eluting stent (X-EES) in terms of the primary end point in-stent late lumen loss at 9 months., Methods and Results: A total of 452 patients were randomly assigned 2:1 to treatment with O-SES (298 patients, 332 lesions) or X-EES (154 patients, 173 lesions) in a multicenter, noninferiority trial. The primary end point was in-stent late loss at 9 months. O-SES was noninferior to X-EES for the primary end point (0.10±0.32 versus 0.11±0.29 mm; difference=0.00063 mm; 95% confidence interval, -0.06 to 0.07; Pnoninferiority<0.0001). Clinical outcome showed similar rates of target-lesion failure at 1 year (O-SES 6.5% versus X-EES 8.0%; hazard ratio=0.82; 95% confidence interval, 0.40-1.68; log-rank test: P=0.58) without cases of stent thrombosis. A subgroup of patients (n=55) underwent serial optical coherence tomography at 9 months, which demonstrated similar neointimal thickness among lesions allocated to O-SES and X-EES (0.10±0.04 mm versus 0.11±0.04 mm; -0.01 [-0.04, -0.01]; P=0.37). Another subgroup of patients (n=56) underwent serial intravascular ultrasound at baseline and 9 months indicating a potential difference in neointimal area at follow-up (O-SES, 0.16±0.33 mm(2) versus X-EES, 0.43±0.56 mm(2); P=0.04)., Conclusions: Compared with durable polymer X-EES, novel biodegradable polymer-based O-SES was found noninferior for the primary end point in-stent late lumen loss at 9 months. Clinical event rates were comparable without cases of stent thrombosis throughout 1 year of follow-up., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01356888., (© 2013 American Heart Association, Inc.)

Background: Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent., Methods: We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104., Findings: Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014)., Interpretation: In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study., Funding: Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt-chromium drug-eluting stent with silicon carbide-coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro; Biotronik, Bülach, Switzerland) with the durable polymer-based Xience Prime/Xpedition everolimus-eluting stent (EES) (Xience Prime/Xpedition stent, Abbott Vascular, IL) in an all-comers patient population., Design: The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer sirolimus-eluting stents (SES) or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least 1 lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary end point target lesion failure (TLF) is a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for noninferiority, inclusion of 2,060 patients would provide more than 80% power to detect noninferiority of the biodegradable polymer SES compared with the durable polymer EES at a 1-sided type I error of 0.05. Clinical follow-up will be continued through 5 years., Conclusion: The BIOSCIENCE trial will determine whether the biodegradable polymer SES is noninferior to the durable polymer EES with respect to TLF., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: This study sought to determine whether the 1-year differences in major adverse cardiac event between a stent eluting biolimus from a biodegradable polymer and bare-metal stents (BMSs) in the COMFORTABLE trial (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) were sustained during long-term follow-up., Methods and Results: A total of 1161 patients were randomly assigned to biolimus-eluting stent (BES) and BMS at 11 centers, and follow-up rates at 2 years were 96.3%. A subgroup of 103 patients underwent angiography at 13 months. At 2 years, differences in the primary end point of cardiac death, target-vessel myocardial infarction, and target lesion revascularization continued to diverge in favor of BES-treated patients (5.8%) compared with BMS-treated patients (11.9%; hazard ratio = 0.48; 95% confidence interval, 0.31-0.72; P < 0.001) with a significant risk reduction during the second year of follow-up (hazard ratio 1-2 years = 0.45; 95% confidence interval, 0.20-1.00; P = 0.049). Differences in the primary end point were driven by a reduction in target lesion revascularization (3.1% versus 8.2%; P < 0.001) and target-vessel reinfarction (1.3% versus 3.4%; P = 0.023). The composite of death, any reinfarction and revascularization (14.5% versus 19.3%; P = 0.03), and cardiac death or target-vessel myocardial infarction (4.2% versus 7.2%; P = 0.036) were less frequent among BES-treated patients compared with BMS-treated patients. The 13-month angiographic in-stent percent diameter stenosis amounted to 12.0 ± 7.2 in BES- and 39.6 ± 25.2 in BMS-treated lesions (P < 0.001)., Conclusions: Among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, BES continued to improve cardiovascular events compared with BMS beyond 1 year., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NTC00962416., (© 2014 American Heart Association, Inc.)

Objectives: This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI)., Background: Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES., Methods: Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year., Results: Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS., Conclusions: Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Newer-generation everolimus-eluting stents (EES) have been shown to improve clinical outcomes compared with early-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in patients undergoing percutaneous coronary intervention (PCI). Whether this benefit is maintained among patients with saphenous vein graft (SVG) disease remains controversial., Methods and Results: We assessed cumulative incidence rates (CIR) per 100 patient years after inverse probability of treatment weighting to compare clinical outcomes. The pre-specified primary endpoint was the composite of cardiac death, myocardial infarction (MI), and target vessel revascularisation (TVR). Out of 12,339 consecutively treated patients, 288 patients (5.7%) underwent PCI of at least one SVG lesion with EES (n=127), SES (n=103) or PES (n=58). Up to four years, CIR of the primary endpoint were 58.7 for EES, 45.2 for SES and 45.6 for PES with similar adjusted risks between groups (EES vs. SES; HR 0.94, 95% CI: 0.55-1.60, EES vs. PES; HR 1.07, 95% CI: 0.60-1.91). Adjusted risks showed no significant differences between stent types for cardiac death, MI and TVR., Conclusions: Among patients undergoing PCI for SVG lesions, newer-generation EES have similar safety and efficacy to early-generation SES and PES during long-term follow-up to four years.

Background: Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up., Methods: Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis., Results: The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE., Conclusion: In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up., (© 2013.)

Background: There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES)., Methods: We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4 years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis., Results: Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4 years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio = 0.95, 95% CI = 0.74-1.21, P = 0.67). Target lesion revascularization was also comparable between the groups (hazard ratio = 0.89, 95% CI = 0.65-1.22, P = 0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio = 0.52, 95% CI = 0.28-0.96, P = 0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4 years (hazard ratio = 0.15, 95% CI = 0.03-0.70, P = 0.02)., Conclusions: In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4 years. Rates of stent thrombosis were significantly lower with BP-DES., (© 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)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess stent strut coverage, malapposition, protrusion, and coronary evaginations as markers of healing 5 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), by optical coherence tomography (OCT)., Background: Early-generation drug-eluting stents have been shown to delay vascular healing., Methods: A total of 88 event-free patients with 1 randomly selected lesion were suitable for final OCT analysis 5 years after drug-eluting stent implantation. The analytical approach was based on a hierarchical Bayesian random-effects model., Results: OCT analysis was performed at 5 years in 41 SES lesions with 6,380 struts, and in 47 PES lesions with 6,782 struts. A total of 196 struts were uncovered in SES (1.5%) compared with 185 struts in PES lesions (1.0%, 95% credibility interval [CrI]: 0.5 to 1.6; p = 0.32). Malapposed struts were present in 1.2% of SES compared with 0.7% of PES struts (0.7%, 95% CrI: 0.03 to 1.6; p = 0.23). Protruding struts were more frequent among SES (n = 114; 0.8%) than PES lesions (n = 24; 0.1%, 95% CrI: 0.3 to 1.3; p < 0.01). Coronary evaginations were more common among SES- than PES-treated lesions (17 vs. 7 per 100 cross sections, p = 0.003). During extended clinical follow-up, 2 patients suffered from very late stent thrombosis showing a high degree of malapposition, protrusion, and coronary evaginations at the time of OCT investigation., Conclusions: Early-generation drug-eluting stents show a similar degree of strut coverage and malapposition at 5 years of follow-up. Despite an overall low degree of uncovered and malapposed struts in event-free patients, some lesions show a clustering of these characteristics, indicating a heterogeneous healing response, which may be the source for very late adverse events., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Context: The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)., Objective: To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI., Design, Setting, and Patients: A prospective, randomized, single-blinded, controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Clinical follow-up was performed at 1 and 12 months., Intervention: Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582)., Main Outcome Measures: Primary end point was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year., Results: Major adverse cardiac events at 1 year occurred in 24 patients (4.3%) receiving biolimus-eluting stents with biodegradable polymer and 49 patients (8.7%) receiving bare-metal stents (hazard ratio [HR], 0.49; 95% CI, 0.30-0.80; P = .004). The difference was driven by a lower risk of target vessel-related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.20; 95% CI, 0.06-0.69; P = .01) and ischemia-driven target-lesion revascularization (9 [1.6%] vs 32 [5.7%]; HR, 0.28; 95% CI, 0.13-0.59; P < .001) in patients receiving biolimus-eluting stents compared with those receiving bare-metal stents. Rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%], P = .53). Definite stent thrombosis occurred in 5 patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%; HR, 0.42; 95% CI, 0.15-1.19; P = .10) treated with bare-metal stents., Conclusion: Compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI., Trial Registration: clinicaltrials.gov Identifier: NCT00962416.

Background: Early generation drug-eluting stents (DESs) reduce restenosis and repeat revascularization procedures. However, the long-term safety and efficacy of early generation DES according to diabetic status are poorly established., Methods: A total of 1,012 patients were randomly assigned to treatment with sirolimus-eluting (n = 503) or paclitaxel-eluting stents (n = 509). Serial angiographic follow-up at baseline, 8 months, and 5 years was available in 293 patients with 382 lesions. The primary end point was a composite of major adverse cardiac events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization). Clinical and angiographic outcomes through 5-year follow-up were compared between diabetic and nondiabetic patients., Results: Major adverse cardiac events were more common among diabetic than nondiabetic patients at 5 years (25.9% vs 19.2%, hazard ratio [HR] 1.45, 95% CI 1.06-1.99, P = .02). The difference in disfavor of diabetic patients was largely determined by a higher rate of cardiac mortality (11.4% vs 4.3%, HR 2.86, 95% CI 1.69-4.84, P < .0001), whereas the risk of myocardial infarction (6.5% vs 6.8%, HR 1.00, 95% CI 0.55-1.84, P = .99) and ischemia-driven target lesion revascularization (14.4% vs 14.1%, HR 1.09, 95% CI 0.73-1.64, P = .67) was comparable. The risk of stent thrombosis was similar among diabetic and nondiabetic patients (definite or probable: 6.0% vs 4.6%, HR 1.36, 95% CI 0.71-2.67, P = .35). Among 293 patients undergoing serial angiography, very-late lumen loss amounted to 0.42 ± 0.63 mm in diabetic patients and 0.44 ± 0.68 mm in nondiabetic patients (P = .79)., Conclusions: Diabetic patients remain at increased risk for mortality after revascularization with early generation DES during long-term follow-up. Conversely, diabetes is no longer associated with an increased risk of clinical and angiographic restenosis after revascularization with early generation DES., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Aims: The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES)., Methods and Results: We pooled individual patient data from three large-scale multicentre randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4, and LEADERS) comparing biodegradable polymer DES with durable polymer SES and assessed clinical outcomes during follow-up through 4 years. The efficacy endpoint of interest was target lesion revascularization and the safety endpoint of interest was definite stent thrombosis. Out of 4062 patients included in the present analysis, 2358 were randomly assigned to treatment with biodegradable polymer DES (sirolimus-eluting, n= 1501; biolimus-eluting, n= 857) and 1704 patients to durable polymer SES. No heterogeneity across the trials was observed in analyses of the primary and secondary endpoints. At 4 years, the risk of target lesion revascularization was significantly lower among patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.82, 95% CI 0.68-0.98, P= 0.029). In addition, the risk of stent thrombosis was significantly reduced with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.56, 95% CI 0.35-0.90, P= 0.015), driven by a lower risk of very late stent thrombosis (hazard ratio 0.22, 95% CI 0.08-0.61, P= 0.004). In keeping with this, in landmark analysis between 1 and 4 years, the incidence of myocardial infarction was lower for patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.59, 95% CI 0.73-0.95, P= 0.031)., Conclusion: Biodegradable polymer DES improve safety and efficacy compared with durable polymer SES during long-term follow-up to 4 years.

Aims: Compared with bare metal stents (BMS), early generation drug-eluting stents (DES) reduce the risk of revascularisation in patients with ST-elevation myocardial infarction (STEMI) at the expense of an increased risk of very late stent thrombosis (ST). Durable polymer coatings for controlled drug release have been identified as a potential trigger for these late adverse events and this has led to the development of newer generation DES with durable and biodegradable polymer surface coatings with improved biocompatibility. In a recent all-comers trial, biolimus-eluting stents with a biodegradable polymer surface coating were found to reduce the risk of very late ST by 80% compared with sirolimus-eluting stents with durable polymer, which also translated into a lower risk of cardiac death and myocardial infarction (MI) beyond one year., Methods and Results: The multicentre COMFORTABLE AMI trial (NCT00962416) randomly assigned 1,161 patients to treatment with biolimus-eluting stents with biodegrable polymer and bare metal stents of otherwise identical design at 11 international sites. The primary endpoint is a composite of cardiac death, target-vessel MI and target lesion revascularisation at one year. Assuming a relative risk reduction of 40% in event rates of the primary endpoint in favour of biolimus-eluting stents with biodegradable polymer, 1,064 patients will provide 80% power to demonstrate superiority. Clinical follow-up will be continued through five years., Conclusions: The COMFORTABLE AMI trial will determine whether biolimus-eluting stents with biodegradable polymer are superior to bare metal stents of otherwise identical design. This is the first randomised controlled trial (RCT) investigating DES with a biodegradable polymer surface coating for drug release in the treatment of patients with STEMI.

Objectives: The goal of this study was to compare the long-term clinical outcome between everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) in patients with acute coronary syndromes (ACS)., Background: EES have not been directly compared with SES in ACS patients to date., Methods: Between 2004 and 2009, 1,746 consecutive ACS patients (ST-segment elevation ACS [STE-ACS]: 33.5%; non-ST-segment elevation ACS [NSTE-ACS]: 66.5%) were treated with EES (n=903) or SES (n=843). Using propensity score matching, clinical outcome was compared among 705 matched pairs of ACS patients treated with EES and SES., Results: Through 3 years, the primary endpoint-the composite of death, myocardial infarction (MI), and target vessel revascularization (TVR)-occurred in 13.8% of EES- and 17.7% of SES-treated ACS patients (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.54 to 0.95, p=0.02). The difference in favor of EES was driven by a lower risk of TVR (5.7% vs. 8.8%, HR: 0.65, 95% CI: 0.43 to 0.98, p=0.04) and a trend toward a lower risk of MI (2.1% vs. 3.3%, HR: 0.56, 95% CI: 0.29 to 1.12, p=0.10). The risk of death (7.2% vs. 8.8%, HR: 0.75, 95% CI: 0.50 to 1.10, p=0.14) showed no difference between EES and SES. The treatment effect in favor of EES for the primary endpoint was similar for patients with STE-ACS (16.4% vs. 18.5%, HR: 0.80, 95% CI: 0.50 to 1.27) and NSTE-ACS (12.4% vs. 17.3%; HR: 0.67, 95% CI: 0.47 to 0.96; pfor interaction=0.56) and across major subgroups. Definite (0.4% vs. 1.8%, p=0.03), and definite or probable stent thrombosis (3.4% vs. 6.1%, p=0.02) were less frequent among EES- than SES-treated ACS patients., Conclusions: Among patients with ACS, the unrestricted use of EES is associated with improved clinical outcome compared with SES during long-term follow-up to 3 years. Notably, the risk of stent thrombosis was lower among EES-treated ACS patients., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We performed a propensity score matched analysis to explore whether TiNOX stents are superior to paclitaxel- (PES) and sirolimus-eluting stents (SES) in routine clinical practice., Methods and Results: A total of 1,607 patients undergoing implantation of SES, PES or TiNOX stents were prospectively entered into a stent registry and followed up for three years. Using propensity score matching, we compared clinical outcome among 319 pairs of patients treated with TiNOX stents or SES and 337 pairs of patients treated with TiNOX stents or PES. The primary outcome MACE, a composite of death, myocardial infarction, and target vessel revascularisation occurred in 20% of patients with TiNOX stents, 19% of patients with SES and 23% of patients with PES at 3-years. The hazard ratio was 1.00 comparing TiNOX stents with SES (95% CI 0.69-1.45, p=1.00), and 0.95 comparing TiNOX stents with PES (95% CI 0.66-1.36, p=0.78)., Conclusion: We did not find evidence to suggest superiority of TiNOX stents over SES or PES. In view of similar clinical outcomes, but with the reduced duration of dual antiplatelet therapy used with the TiNOX stent, we suggest that TiNOX stents may be an alternative to drug-eluting stents in patients unsuitable for long-term dual antiplatelet therapy.

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., Methods: 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., Findings: 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)., Interpretation: 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., Funding: Biosensors Europe SA, Switzerland., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: This study sought to investigate safety and efficacy of biolimus-eluting stents (BES) with biodegradable polymer as compared with sirolimus-eluting stents (SES) with durable polymer through 2 years of follow-up., Background: BES with a biodegradable polymer provide similar efficacy and safety as SES with a durable polymer at 9 months. Clinical outcomes beyond the period of biodegradation of the polymer used for drug release and after discontinuation of dual antiplatelet therapy are of particular interest., Methods: A total of 1,707 patients were randomized to unrestricted use of BES (n = 857) or SES (n = 850) in an all-comers patient population., Results: At 2 years, BES remained noninferior compared with SES for the primary endpoint, which was a composite of cardiac death, myocardial infarction, or clinically indicated target vessel revascularization (BES 12.8% vs. SES 15.2%, hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.65 to 1.08, p(noninferiority) < 0.0001, p(superiority) = 0.18). Rates of cardiac death (3.2% vs. 3.9%, HR: 0.81, 95% CI: 0.49 to 1.35, p = 0.42), myocardial infarction (6.3% vs. 5.6%, HR: 1.12, 95% CI: 0.76 to 1.65, p = 0.56), and clinically indicated target vessel revascularization (7.5% vs. 8.6%, HR: 0.86, 95% CI: 0.62 to 1.20, p = 0.38) were similar for BES and SES. The rate of definite stent thrombosis through 2 years was 2.2% for BES and 2.5% for SES (p = 0.73). For the period between 1 and 2 years, event rates for definite stent thrombosis were 0.2% for BES and 0.5% for SES (p = 0.42). After discontinuation of dual antiplatelet therapy, no very late definite stent thrombosis occurred in the BES group., Conclusions: At 2 years of follow-up, the unrestricted use of BES with a biodegradable polymer maintained a similar safety and efficacy profile as SES with a durable polymer. (Limus Eluted From a Durable Versus Erodable Stent Coating [LEADERS]; NCT00389220)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Long-term comparative data of first-generation drug-eluting stents are scarce. We investigated clinical and angiographic outcomes of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) at 5 years as part of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) LATE study., Methods and Results: A total of 1012 patients were randomly assigned to SES or PES. Repeat angiography was completed in 444 of 1012 patients (43.8%) at 5 years. Major adverse cardiac events occurred in 19.7% of SES- and 21.4% of PES-treated patients (hazard ratio, 0.89; 95% confidence interval, 0.68 to 1.17; P=0.39) at 5 years. There were no differences between SES and PES in terms of cardiac death (5.8% versus 5.7%; P=0.35), myocardial infarction (6.6% versus 6.9%; P=0.51), and target lesion revascularization (13.1% versus 15.1%; P=0.29). Between 1 and 5 years, the annual rate of target lesion revascularization was 2.0% (95% confidence interval, 1.4% to 2.6%) for SES and 1.4% (95% confidence interval, 0.9% to 2.0%) for PES. Among patients undergoing paired angiography at 8 months and 5 years, delayed lumen loss amounted to 0.37 ± 0.73 mm for SES and 0.29 ± 0.59 mm for PES (P=0.32). The overall rate of definite stent thrombosis was 4.6% for SES and 4.1% for PES (P=0.74), and very late definite stent thrombosis occurred at an annual rate of 0.65% (95% confidence interval, 0.40% to 0.90%)., Conclusions: Long-term follow-up of first-generation drug-eluting stents shows no significant differences in clinical and angiographic outcomes between SES and PES. The continuous increase in late lumen loss in conjunction with the ongoing risk of very late stent thrombosis suggests that vascular healing remains incomplete up to 5 years after implantation of first-generation drug-eluting stents.

Objectives: This study sought to compare the efficacy of passive stent coating with titanium-nitride-oxide (TiNO) with drug-eluting stents releasing zotarolimus (ZES) (Endeavor, Medtronic, Minneapolis, Minnesota)., Background: Stent coating with TiNO has been shown to reduce restenosis compared with bare-metal stents in experimental and clinical studies., Methods: In an assessor-blind noninferiority study, 302 patients undergoing percutaneous coronary intervention were randomized to treatment with TiNO or ZES. The primary endpoint was in-stent late loss at 6 to 8 months, and analysis was by intention to treat., Results: Both groups were well balanced with respect to baseline clinical and angiographic characteristics. The TiNO group failed to reach the pre-specified noninferiority margin for the primary endpoint (in-stent late loss: 0.64 ± 0.61 mm vs. 0.47 ± 0.48 mm, difference: 0.16, upper 1-sided 95% confidence interval [CI]: 0.26; p(noninferiority) = 0.54), and subsequent superiority testing was in favor of ZES (p(superiority) = 0.02). In-segment binary restenosis was lower with ZES (11.1%) than with TiNO (20.5%; p(superiority) = 0.04). A stratified analysis of the primary endpoint found particularly pronounced differences between stents among diabetic versus nondiabetic patients (0.90 ± 0.69 mm vs. 0.39 ± 0.38 mm; p(interaction) = 0.04). Clinical outcomes showed a similar rate of death (0.7% vs. 0.7%; p = 1.00), myocardial infarction (5.3% vs. 6.7%; p = 0.60), and major adverse cardiac events (21.1% vs. 18.0%, hazard ratio: 1.19, 95% CI: 0.71 to 2.00; p = 0.50) at 1 year. There were no differences in rates of definite or probable stent thrombosis (0.7% vs. 0%; p = 0.51) at 1 year., Conclusions: Compared with TiNO, ZES was superior with regard to late loss and binary restenosis. The concept of passive stent coating with TiNO remains inferior to drug-eluting stent technology in reducing restenosis. ([TIDE] Randomized Trial Comparing Titan Stent With Zotarolimus-Eluting Stent: NCT00492908)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to compare the unrestricted use of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention., Background: It is unclear whether there are differences in safety and efficacy between EES and SES during long-term follow-up., Methods: Using propensity score matching, clinical outcome was compared among 1,342 propensity score-matched pairs of patients treated with EES and SES. The primary outcome was a composite of death, MI, and target vessel revascularization., Results: The median follow-up was 1.5 years with a maximum of 3 years. The primary outcome occurred in 14.9% of EES- and 18.0% of SES-treated patients up to 3 years (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.68 to 1.00, p = 0.056). All-cause mortality (6.0% vs. 6.5%, HR: 0.92, 95% CI: 0.68 to 1.25, p = 0.59) was similar, risks of myocardial infarction (MI) (3.3% vs. 5.0%, HR: 0.62, 95% CI: 0.42 to 0.92, p = 0.017), and target vessel revascularization (7.0% vs. 9.6%, HR: 0.75, 95% CI: 0.57 to 0.99, p = 0.039) were lower with EES than SES. Definite stent thrombosis (ST) (HR: 0.30, 95% CI: 0.12 to 0.75, p = 0.01) was less frequent among patients treated with EES. The reduced rate of MI with EES was explained in part by the lower risk of definite ST and the corresponding decrease in events associated with ST (HR: 0.25, 95% CI: 0.08 to 0.75, p = 0.013)., Conclusions: The unrestricted use of EES appears to be associated with improved clinical long-term outcome compared with SES. Differences in favor of EES are driven in part by a lower risk of MI associated with ST., (2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: This study investigated the differences in clinical outcomes between patients with bifurcation lesions (BL) treated with a biolimus-eluting stent (BES) with a biodegradable polymer, and a sirolimus-eluting stent (SES) with a durable polymer., Methods and Results: The clinical outcomes were assessed in the 497 patients (BES 258, SES 239) enrolled in the multicentre, randomised LEADERS trial who underwent treatment of ≥1 BL (total=534 BL). At 12-months follow-up there was no significant difference in the primary endpoint of MACE, a composite of cardiac death, myocardial infarction and clinically indicated target vessel revascularisation (BES 12.8% vs. SES 16.3%, p=0.31). Patients treated with BES had comparable rates of cardiac death (BES 2.7% vs. SES 2.9%, p=1.00), numerically higher rates of myocardial infarction (BES 8.9% vs. SES 5.4%, p=0.17), and significantly lower rates of clinically indicated target vessel revascularisation (4.3% vs. 11.3%, p=0.004) when compared to those treated with SES. The rate of stent thrombosis at 12-months was 4.3% and 3.8% for BES and SES, respectively (p=0.82)., Conclusions: In the treatment of BL the use of BES lead to superior efficacy and comparable safety compared to SES.

Objectives: We aimed at comparing the long term clinical outcome of SES and PES in routine clinical practice., Background: Although sirolimus-eluting stents (SES) more effectively reduce neointimal hyperplasia than paclitaxel-eluting stents (PES), uncertainty prevails whether this difference translates into differences in clinical outcomes outside randomized controlled trials with selected patient populations and protocol-mandated angiographic follow-up., Methods: Nine hundred and four consecutive patients who underwent implantation of a drug-eluting stent between May 2004 and February 2005: 467 patients with 646 lesions received SES, 437 patients with 600 lesions received PES. Clinical follow-up was obtained at 2 years without intervening routine angiographic follow-up. The primary endpoint was a composite of death, myocardial infarction (MI), or target vessel revascularization (TVR)., Results: At 2 years, the primary endpoint was less frequent with SES (12.9%) than PES (17.6%, HR = 0.70, 95% CI 0.50-0.98, P = 0.04). The difference in favor of SES was largely driven by a lower rate of target lesion revascularisation (TLR; 4.1% vs. 6.9%, P = 0.05), whereas rates of death (6.4% vs. 7.6%, P = 0.49), MI (1.9% vs. 3.2%, P = 0.21), or definite stent thrombosis (0.6% vs. 1.4%, P = 0.27) were similar for both stent types. The benefit regarding reduced rates of TLR was significant in nondiabetic (3.6% vs. 7.1%, P = 0.04) but not in diabetic patients (5.6% vs. 6.1%, P = 0.80)., Conclusions: SES more effectively reduced the need for repeat revascularization procedures than PES when used in routine clinical practice. The beneficial effect is maintained up to 2 years and may be less pronounced in diabetic patients., (Copyright © 2010 Wiley-Liss, Inc.)

Aims: This study reports the 12-month clinical outcomes of the LEADERS clinical trial which compared a biolimus eluting stent with a biodegradable polymer (BES) to a sirolimus eluting stent with a durable polymer (SES)., Methods and Results: The multicentre LEADERS trial employed an all-comers approach to recruit 1,707 patients who were randomised to treatment with either BES (n=857) or SES (n=850) in a non-inferiority design. The primary clinical endpoint of this study was a composite of cardiac death, myocardial infarction and clinical-indicated target vessel revascularisation. Follow-up was obtained in 97.6% of patients. At 12 months, BES remained non-inferior compared to SES for the primary endpoint (BES 10.6% vs. SES 12.0%, HR:0.88, 95% CI:0.66-1.17, p=0.37). Rates of cardiac death (2.1% vs. 2.7%, HR:0.77, 95% CI:0.42-1.44, p=0.42), MI (5.8% vs. 4.6%, HR:1.27, 95% CI:0.84-1.94, p=0.26) and clinically-indicated target vessel revascularisation (5.8% vs. 7.1%, HR:0.82, 95%CI:0.56-1.19, p=0.29) were similar for BES and SES. Similarly, there was no difference in the incidence of definite stent thrombosis at 12 months., Conclusions: These findings support the safety and efficacy of the BES stent with a biodegradable polymer at 12-month clinical follow-up, and suggest it is a suitable alternative to the SES stent with a durable polymer.

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aims: Incomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial., Methods and Results: Fifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference -1.4%, 95% confidence interval (CI) -3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had > or =5% of all struts uncovered (difference -33.1%, 95% CI -61.7 to -10.3, P < 0.01)., Conclusion: Strut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determined.

Aims: Lesion length remains a predictor of target lesion revascularisation and results of long lesion stenting remain poor. Sirolimus-eluting stents have been shown to perform better than paclitaxel eluting stents in long lesions. In this substudy of the LEADERS trial, we compared the performance of biolimus biodegradable polymer (BES) and sirolimus permanent polymer stents (SES) in long lesions., Methods and Results: A total of 1,707 'all-comer' patients were randomly allocated to treatment with BES and SES. A stratified analysis of angiographic and clinical outcomes at nine months and one year, respectively was performed for vessels with lesion length <20 mm versus >20 mm (as measured by quantitative angiography).Of 1,707 patients, 592 BES patients with 831 lesions and 619 SES patients with 876 lesions had only short lesions treated. One hundred and fifty-three BES patients with 166 lesions and 151 SES patients with 162 lesions had long lesions. There were no significant differences in baseline clinical characteristics, except for higher number of patients with long lesions presenting with acute myocardial infarction in both stent groups. Long lesions tended to have lower MLD and greater percent diameter stenosis at baseline than short lesions. Late loss was greater for long lesions than short lesions. There was no statistically significant difference in late loss between BES and SES stents (0.32+/-0.69 vs 0.24+/-0.57, p=0.59). Binary in-segment restenosis was present in 23.2% versus 13.1% of long lesions treated with BES and SES, respectively (p=0.042). In patients with long lesions, the overall MACE rate was similar for BES and SES (17% vs 14.6%; p=0.62). There was a trend towards higher overall TLR rate with BES (12.4 % vs 6.0%; HR=2.06; p=0.07) and clinically driven TLR (10.5% vs 5.3%: HR 1.94; p=0.13). Rates of definite stent thrombosis were 3.3% in the long lesion group and 1.3-1.7 % in the short lesion group., Conclusions: BES and SES appear similar with respect to MACE in long lesions in this "all-comer" patient population. However, long lesions tended to have a higher rate of binary in-segment restenosis and TLR following BES than SES treatment.

Background: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer)., Methods: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220., Findings: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26)., Interpretation: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes., Funding: Biosensors Europe SA, Switzerland.

Aims: Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents., Methods and Results: In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years., Conclusion: Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients.

Objectives: Our purpose was to make a synthesis of the available evidence on the relative efficacy and safety of 2 drug-eluting stents (DES)--sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES)--in patients with coronary artery disease., Background: It is not known whether there are differences in late outcomes between the 2 most commonly used DES: SES and PES., Methods: Sixteen randomized trials of SES versus PES with a total number of 8,695 patients were included in this meta-analysis. A full set of individual outcome data from 5,562 patients was also available. Mean follow-up period ranged from 9 to 37 months. The primary efficacy end point was the need for reintervention (target lesion revascularization). The primary safety end point was stent thrombosis. Secondary end points were death and recurrent myocardial infarction (MI)., Results: No significant heterogeneity was found across trials. Compared with PES, SES significantly reduced the risk of reintervention (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 to 0.87, p < 0.001) and stent thrombosis (HR 0.66; 95% CI 0.46 to 0.94, p = 0.02) without significantly impacting on the risk of death (HR 0.92; 95% CI 0.74 to 1.13, p = 0.43) or MI (HR 0.84; 95% CI 0.69 to 1.03, p = 0.10)., Conclusions: Sirolimus-eluting stents are superior to PES in terms of a significant reduction of the risk of reintervention and stent thrombosis. The risk of death was not significantly different between the 2 DES, but there was a trend toward a higher risk of MI with PES, especially after the first year from the procedure.

Objectives: We assessed the impact of vessel size on angiographic and long-term clinical outcome after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) within a randomized trial (SIRTAX [Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization])., Background: Percutaneous coronary intervention in small-vessel disease is associated with an increased risk of major adverse cardiac events (MACE)., Methods: A total of 1,012 patients were randomly assigned to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of angiographic and clinical outcome was performed up to 2 years after PCI according to size of the treated vessel (reference vessel diameter < or =2.75 vs. >2.75 mm)., Results: Of 1,012 patients, 370 patients (37%) with 495 lesions underwent stent implantation in small vessels only, 504 patients (50%) with 613 lesions in large vessels only, and 138 patients (14%) with 301 lesions in both small and large vessels (mixed). In patients with small-vessel stents, SES reduced MACE by 55% (10.4% vs. 21.4%; p = 0.004), mainly driven by a 69% reduction of target lesion revascularization (TLR) (6.0% vs. 17.7%; p = 0.001) compared with PES at 2 years. In patients with large- and mixed-vessel stents, rates of MACE (large: 10.4% vs. 13.1%; p = 0.33; mixed: 16.7% vs. 18.0%; p = 0.83) and TLR (large: 6.9% vs. 8.6%; p = 0.47; mixed: 16.7% vs. 15.4%; p = 0.86) were similar for SES and PES. There were no significant differences with respect to death and myocardial infarction between the 3 groups., Conclusions: Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http://clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661).

Background: Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents., Methods: We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation., Findings: Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021)., Interpretation: The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Background: Stent thrombosis is a safety concern associated with use of drug-eluting stents. Little is known about occurrence of stent thrombosis more than 1 year after implantation of such stents., Methods: Between April, 2002, and Dec, 2005, 8146 patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES; n=3823) or paclitaxel-eluting stents (PES; n=4323) at two academic hospitals. We assessed data from this group to ascertain the incidence, time course, and correlates of stent thrombosis, and the differences between early (0-30 days) and late (>30 days) stent thrombosis and between SES and PES., Findings: Angiographically documented stent thrombosis occurred in 152 patients (incidence density 1.3 per 100 person-years; cumulative incidence at 3 years 2.9%). Early stent thrombosis was noted in 91 (60%) patients, and late stent thrombosis in 61 (40%) patients. Late stent thrombosis occurred steadily at a constant rate of 0.6% per year up to 3 years after stent implantation. Incidence of early stent thrombosis was similar for SES (1.1%) and PES (1.3%), but late stent thrombosis was more frequent with PES (1.8%) than with SES (1.4%; p=0.031). At the time of stent thrombosis, dual antiplatelet therapy was being taken by 87% (early) and 23% (late) of patients (p<0.0001). Independent predictors of overall stent thrombosis were acute coronary syndrome at presentation (hazard ratio 2.28, 95% CI 1.29-4.03) and diabetes (2.03, 1.07-3.83)., Interpretation: Late stent thrombosis was encountered steadily with no evidence of diminution up to 3 years of follow-up. Early and late stent thrombosis were observed with SES and with PES. Acute coronary syndrome at presentation and diabetes were independent predictors of stent thrombosis.

Background: Sirolimus-eluting stents and paclitaxel-eluting stents, as compared with bare-metal stents, reduce the risk of restenosis. It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents., Methods: We conducted a randomized, controlled, single-blind trial comparing sirolimus-eluting stents with paclitaxel-eluting stents in 1012 patients undergoing percutaneous coronary intervention. The primary end point was a composite of major adverse cardiac events (death from cardiac causes, myocardial infarction, and ischemia-driven revascularization of the target lesion) by nine months. Follow-up angiography was completed in 540 of 1012 patients (53.4 percent)., Results: The two groups had similar baseline clinical and angiographic characteristics. The rate of major adverse cardiac events at nine months was 6.2 percent in the sirolimus-stent group and 10.8 percent in the paclitaxel-stent group (hazard ratio, 0.56; 95 percent confidence interval, 0.36 to 0.86; P=0.009). The difference was driven by a lower rate of target-lesion revascularization in the sirolimus-stent group than in the paclitaxel-stent group (4.8 percent vs. 8.3 percent; hazard ratio, 0.56; 95 percent confidence interval, 0.34 to 0.93; P=0.03). Rates of death from cardiac causes were 0.6 percent in the sirolimus-stent group and 1.6 percent in the paclitaxel-stent group (P=0.15); the rates of myocardial infarction were 2.8 percent and 3.5 percent, respectively (P=0.49); and the rates of angiographic restenosis were 6.6 percent and 11.7 percent, respectively (P=0.02)., Conclusions: As compared with paclitaxel-eluting stents, the use of sirolimus-eluting stents results in fewer major adverse cardiac events, primarily by decreasing the rates of clinical and angiographic restenosis., (Copyright 2005 Massachusetts Medical Society.)