Franz Eberli

Triemli City Hospital, Zürich, Zurich, Switzerland

Are you Franz Eberli?

Claim your profile

Publications (91)934.08 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. To assess the safety and efficacy of Biolimus A9-eluting stents (BES, BioMatrix™ and BioMatrix Flex™) in routine clinical practice. Background. The LEADERS randomized trial has documented equivalent efficacy and superior safety of the BES when compared to a first generation Sirolimus-eluting Cypher(TM) stent. Methods. 5,472 patients from 57 centers, treated with BES, were enrolled in an international multicenter registry and followed clinically up to 2 years. Results. Mean patient age was 63.2 ± 11 years, 24% of patients had diabetes, and 49.8% presented with an acute coronary syndrome. 99.3% of patients were discharged on dual antiplatelet therapy [DAPT], 83.3% remained on DAPT at 1 year and 30.6% at 2 years. The incidence of the composite primary endpoint (Major Adverse Cardiac [MACE] at 12 months) was 4.5% (cardiac death 0.9%, myocardial infarction 1.7%, clinically indicated target vessel revascularization [ci-TVR] 2.8%). MACE incidence was 6.8% at 24 months (cardiac death 1.5%, myocardial infarction 2.4%, ci-TVR 4.3%). At 12 months, 32 patients (0.6%) had suffered at least one definite or probable stent thrombosis [ST], and 91 patients (1.7%) a major bleed [MB]. Nine patients with ST (27.3%) and 7 patients with a MB (7.7%) died during the first year after the index procedure. Between 12 and 24 months after implantation, there were 18 (0.4%) additional MB and 8 (0.2%) additional ST. Conclusions. This large international cohort documents a low 12 and 24 months MACE incidence and a very low ST incidence in an unselected patient population undergoing BES implantation. The results are in keeping with those of the randomized controlled LEADERS trial. Even though ST with this stent was a rare event, it was still associated with significant mortality. MB remains a problem, and warrants improved tailoring of DAPT in recipients of drug eluting stents. This article is protected by copyright. All rights reserved. Copyright © 2015 Wiley Periodicals, Inc., a Wiley company.
    Catheterization and Cardiovascular Interventions 02/2015; DOI:10.1002/ccd.25892 · 2.40 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-months dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined. Methods Definite/probable ST and MB (TIMI major and BARC ≥3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, i.e., BASKET (6 months, n = 557) and BASKET-PROVE (12 months, n = 2,314), between months 0–6 (DAPT in both trials), 7–12 (DAPT in BASKET-PROVE only), and 13–24 (aspirin in both trials) using propensity score adjusted time-stratified Cox proportional-hazard models. Results Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period p = 0.145) but an inconsistent pattern for MB (interaction DAPT/period p < 0.001 for TIMI major and p = 0.046 for BARC ≥3), with more MB occurring during months 7–12 with prolonged DAPT. Considering observed case-fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST-deaths and the excess of 5 MB-deaths resulted in an expected benefit of 22 survivors/10’000 patients treated over 2 years with prolonged DAPT. Conclusion Despite overall low event rates, prolonged DAPT was associated with more MB during months 7–12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST vs. MB, 12-vs. 6-months DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.
    American Heart Journal 07/2014; 168(5). DOI:10.1016/j.ahj.2014.07.019 · 4.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 12.07.2 in BES- and 39.625.2 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.
    Circulation Cardiovascular Interventions 05/2014; 7(3). DOI:10.1161/CIRCINTERVENTIONS.113.001440 · 6.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Importance In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy. Objective To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin. Design, Setting, and Patients Phase 3, 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries. Interventions Patients (n = 2067) were randomized to 1 of 24 treatment groups in 2 steps. Patients were initially randomized to a daily, moderate-intensity (atorvastatin [10 mg], simvastatin [40 mg], or rosuvastatin [5 mg]) or high-intensity (atorvastatin [80 mg], rosuvastatin [40 mg]) statin. After a 4-week lipid-stabilization period, patients (n = 1899) were randomized to compare evolocumab (140 mg every 2 weeks or 420 mg monthly) with placebo (every 2 weeks or monthly) or ezetimibe (10 mg or placebo daily; atorvastatin patients only) when added to statin therapies. Main Outcomes and Measures Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) level at the mean of weeks 10 and 12 and at week 12. Results Evolocumab reduced LDL-C levels by 66% (95% CI, 58% to 73%) to 75% (95% CI, 65% to 84%) (every 2 weeks) and by 63% (95% CI, 54% to 71%) to 75% (95% CI, 67% to 83%) (monthly) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; the LDL-C reductions at week 12 were comparable. For moderate-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36%, 40%, and 39% of evolocumab-, ezetimibe-, and placebo-treated patients, respectively. The most common adverse events in evolocumab-treated patients were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%). Conclusions and Relevance In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia, evolocumab added to moderate- or high-intensity statin therapy resulted in additional LDL-C lowering. Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering. Trial Registration clinicaltrials.gov Identifier: NCT01763866
    JAMA The Journal of the American Medical Association 05/2014; 14(311(18)):1870-82. DOI:10.1001/jama.2014.4030. · 30.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents.
    BMJ Clinical Research 01/2014; 349:g6427. · 14.09 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. 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. 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). 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).
    JACC. Cardiovascular Interventions 08/2013; 6(8):777-89. DOI:10.1016/j.jcin.2013.04.011 · 7.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Few data are available concerning the impact of gender on temporal trends in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: All STEMI patients consecutively enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus project from 1997−2011 were included. Temporal trends in presentation, treatment and outcomes were analyzed using multiple logistic regressions with generalized estimations. Results: Of 21,620 STEMI patients, 5786 were women and 15,834 men from 78 Swiss hospitals. Women were 8.6 years older, presented 48 minutes later with less pain, but more dyspnea, and more frequently had atrial fibrillation (5.5 vs. 3.9%, p<0.001), heart failure (Killip class >2) (9.7 vs. 7.3%, p<0.001), and moderate or severe comorbidities (24.8 vs. 18.2%, p<0.001). Women were less likely to undergo primary reperfusion treatment after adjustment for baseline characteristics and admission year (OR 0.80, 95% CI 0.71−0.90, p<0.001) or receive early and discharge drugs, such as thienopyridines, angiotensin-converting-enzyme inhibitors, angiotensin II receptor antagonists, and statins. In 1997, thrombolysis was performed in 51% of male and 39% of female patients; its use rapidly decreased during the 1990s and has now become negligible. Primary percutaneous coronary intervention increased from under 10% in both genders in 1997 to over 70% in females and over 80% in males since 2006. Patients admitted in cardiogenic shock increased by 8% per year in both genders. The incidence of both reinfarction and cardiogenic shock developing during hospitalization decreased significantly over 15 years while in-hospital mortality decreased from 10 to 5% in men and from 18 to 7% in women. This corresponds to a relative reduction of 5% per year for males (OR 0.95, 95% CI 0.92−0.99, p=0.006) and 6% per year for female STEMI patients (OR 0.94, 95% CI 0.91−0.97, p<0.001). Despite higher crude in-hospital mortality, female gender per se was not an independent predictor of in-hospital mortality (OR 1.07, 95% CI 0.84−1.35, p=0.59). Conclusion: Substantial changes have occurred in presentation, treatment, and outcome of men and women with STEMI in Switzerland over the past 15 years. Although parallel trends were seen in both groups, ongoing disparities in certain treatments remain. However, these did not translate into worse risk-adjusted in-hospital mortality, suggesting that the gender gap in STEMI care may be closing.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Few data are available concerning the impact of gender on temporal trends in patients with acute ST-segment elevation myocardial infarction (STEMI). All STEMI patients consecutively enrolled in the AMIS (Acute Myocardial Infarction in Switzerland) Plus project from 1997-2011 were included. Temporal trends in presentation, treatment and outcomes were analyzed using multiple logistic regressions with generalized estimations. Of 21,620 STEMI patients, 5786 were women and 15,834 men from 78 Swiss hospitals. Women were 8.6 years older, presented 48 minutes later with less pain, but more dyspnea, and more frequently had atrial fibrillation (5.5 vs. 3.9%, p<0.001), heart failure (Killip class >2) (9.7 vs. 7.3%, p<0.001), and moderate or severe comorbidities (24.8 vs. 18.2%, p<0.001). Women were less likely to undergo primary reperfusion treatment after adjustment for baseline characteristics and admission year (OR 0.80, 95% CI 0.71-0.90, p<0.001) or receive early and discharge drugs, such as thienopyridines, angiotensin-converting-enzyme inhibitors, angiotensin II receptor antagonists, and statins. In 1997, thrombolysis was performed in 51% of male and 39% of female patients; its use rapidly decreased during the 1990s and has now become negligible. Primary percutaneous coronary intervention increased from under 10% in both genders in 1997 to over 70% in females and over 80% in males since 2006. Patients admitted in cardiogenic shock increased by 8% per year in both genders. The incidence of both reinfarction and cardiogenic shock developing during hospitalization decreased significantly over 15 years while in-hospital mortality decreased from 10 to 5% in men and from 18 to 7% in women. This corresponds to a relative reduction of 5% per year for males (OR 0.95, 95% CI 0.92-0.99, p=0.006) and 6% per year for female STEMI patients (OR 0.94, 95% CI 0.91-0.97, p<0.001). Despite higher crude in-hospital mortality, female gender per se was not an independent predictor of in-hospital mortality (OR 1.07, 95% CI 0.84-1.35, p=0.59). Substantial changes have occurred in presentation, treatment, and outcome of men and women with STEMI in Switzerland over the past 15 years. Although parallel trends were seen in both groups, ongoing disparities in certain treatments remain. However, these did not translate into worse risk-adjusted in-hospital mortality, suggesting that the gender gap in STEMI care may be closing.
    09/2012; 1(3):183-91. DOI:10.1177/2048872612454021
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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). To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI. 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. Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582). 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. 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. 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. clinicaltrials.gov Identifier: NCT00962416.
    JAMA The Journal of the American Medical Association 08/2012; 308(8):777-87. DOI:10.1001/jama.2012.10065 · 30.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). 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.
    American heart journal 05/2012; 163(5):876-886.e2. DOI:10.1016/j.ahj.2012.02.014 · 4.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.).
    New England Journal of Medicine 03/2012; 366(15):1404-13. DOI:10.1056/NEJMoa1200933 · 54.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known. In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels ≥3 mm in diameter are randomized 1:1:1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy. By the end of 2010, 878 patients (37% of those planned) were enrolled. This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting.
    American heart journal 02/2012; 163(2):136-41.e1. DOI:10.1016/j.ahj.2011.08.023 · 4.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    The Lancet 11/2011; 378(9807):1940-8. DOI:10.1016/S0140-6736(11)61672-3 · 39.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present analysis was performed to evaluate the impact of diabetes mellitus (DM) status on the severity of coronary artery disease (CAD) and current approaches in interventional treatment. Little is known about the effect of DM treated with diet, oral agents, or insulin on lesion characteristics and anatomical pattern of CAD and their interventional treatment. Patients (n = 46,779) of the contemporary Euro Heart Survey PCI registry with known DM status were included in this analysis. Nondiabetics (n = 35,280, 75.4%) were compared with diabetics treated with diet (n = 1,533, 3.3%), oral agents (n = 7,222, 15.4%), and insulin (n = 2,744, 5.8%). Diabetic patients were older, suffered more frequently from comorbidities and presented more often with cardiogenic shock. The number of severely stenosed (≥ 70%) segments incrementally increased from nondiabetics to insulin-requiring diabetics. The location of lesions did not differ between patients with and without DM. The ratio stenosed/treated segments progressively rose among the four patient cohorts. The severity of DM negatively correlated with the extent of complete revascularization. After adjustment for confounding variables no significant differences in hospital mortality could be observed between patients without DM and diabetics treated with diet, but a significantly higher rate of death was seen in diabetic patients with oral medication and insulin therapy. Although CAD was more severe in patients with DM the percentage of treated segments with ≥ 70% stenosis was lower. Adjusted hospital mortality was increased among diabetics treated with oral medication or insulin, but not among those treated with diet.
    Catheterization and Cardiovascular Interventions 11/2011; 78(5):702-9. DOI:10.1002/ccd.22939 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The current study reports clinical outcomes at three year follow-up of the LEADERS clinical trial which was the first all-comers trial comparing a new generation biodegradable polymer biolimus drug-eluting stent (BES) with the first generation permanent polymer sirolimus-eluting stent (SES). One thousand seven hundred and seven patients were randomised to unrestricted use of BES (n=857) or SES (n=850) in an all-comers population. Three year follow-up was available in 95% of the patients, 812 treated with BES and 809 treated with SES. At three years, BES remains non-inferior to SES for the primary endpoint of major adverse cardiac events (composite of cardiac death, myocardial infarction (MI), or clinically-indicated target vessel revascularisation (CI-TVR) (BES 15.7% versus SES 19%; HR 0.82 CI 0.65-1.03; p=0.09). The MACE Kaplan Meier event curves increasingly diverge with the difference in events increasing from 1.4% to 2.4% and 3.3% at 1, 2 and 3 years, respectively in favour of BES. The rate of cardiac death was non-significantly lower 4.2% versus 5.2% (HR=0.81 CI 0.52-1.26; p=0.34) and the rate of myocardial infarction was equivalent 7.2% versus 7.1% (HR 1.01 CI 0.70-1.44; p=0.97) for BES versus SES, respectively. Thus BES was non-inferior to SES in all the safety endpoints. Clinically-indicated TVR occurred in 9.4% of BES treated patients versus 11.1% of SES treated patients (HR 0.84 CI 0.62-1.13; p=0.25). Rates of definite stent thrombosis were 2.2% for BES and 2.9% for SES (HR 0.78 CI 0.43-1.43; p=0.43), with the event rate increase of 0.2% from one to three years for BES and 0.9% for SES. For patients presenting with ST-elevation myocardial infarction BES was superior to SES in reducing MACE. The findings of the three year follow-up support the claim that the biodegradable polymer biolimus-eluting stent has equivalent safety and efficacy to permanent polymer sirolimus-eluting stent in an all-comers patient population. Its performance is superior in some subpopulations such as in ST-elevation MI patients and event rates for BES are overall lower than for SES with a trend toward increasing divergence of outcomes over three years.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 11/2011; 7(7):789-95. DOI:10.4244/EIJV7I7A125 · 3.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the "all-comers" LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 8<SXmid ≤16 (n=472) and SXhigh >16 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046). The SXscore when applied to an "all-comers" patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 09/2011; 7(5):605-13. DOI:10.4244/EIJV7I5A97 · 3.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The percentage of elderly treated with percutaneous coronary intervention (PCI) has been increasing year by year. Little is known about predictors of hospital mortality in elderly undergoing PCI for acute coronary syndromes (ACS) and stable angina. Between 2005 and 2008 a total of 47,407 consecutive patients undergoing PCI were prospectively enrolled into the PCI-Registry of the EHS Programme. For the present analysis patients were divided into four categories: ACS patients ≥ 75 (n=4,943) and < 75 years (n=19,446), and patients with stable angina ≥ 75 (n=3,393) and < 75 years (n=19,625). A multiple logistic regression analysis was conducted to detect independent predictors of mortality in patients ≥ 75 years undergoing PCI. In addition, differences in clinical characteristics, procedural details and in-hospital outcomes between the subgroups were evaluated. Patients ≥ 75 years had more co-morbidities, and more severe coronary pathology. The use of guideline-recommended adjunctive therapy and procedural success was high in all groups. The incidence of in-hospital death was highest in ACS patients ≥ 75 years (5.2%) and < 75 years (1.7%), followed by patients with stable angina ≥ 75 (0.5%) and < 75 years (0.2%). Haemodynamic instability and acute ST-elevation myocardial infarction were the strongest determinants of hospital mortality among patients ≥ 75 years with ACS, whereas interventional complications were the most meaningful predictors of death in older patients undergoing elective PCI. Patients ≥ 75 years undergoing PCI face a relatively low risk of hospital death. However, complication rates were significantly higher compared to younger patients, strongly influenced by clinical, angiographic and interventional variables.
    International journal of cardiology 09/2011; 151(2):164-9. DOI:10.1016/j.ijcard.2010.05.006 · 6.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. 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. 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).
    JACC Cardiovascular Interventions 08/2011; 4(8):887-95. DOI:10.1016/j.jcin.2011.03.017 · 7.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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%). 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.
    Circulation 06/2011; 123(24):2819-28, 6 p following 2828. DOI:10.1161/CIRCULATIONAHA.110.004762 · 14.95 Impact Factor

Publication Stats

3k Citations
934.08 Total Impact Points

Institutions

  • 2011–2014
    • Triemli City Hospital
      Zürich, Zurich, Switzerland
  • 1989–2012
    • University of Zurich
      • Internal Medicine Unit
      Zürich, Zurich, Switzerland
  • 1998–2001
    • Inselspital, Universitätsspital Bern
      • • Swiss Cardiovascular Center Bern
      • • Department of Cardiology
      Berna, Bern, Switzerland
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 1999–2000
    • Whitaker Wellness Institute
      Newport Beach, California, United States
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1997
    • Northeastern University
      Boston, Massachusetts, United States
  • 1992–1993
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States