Papers by Hans-Henrik Tilsted
Circulation: Cardiovascular Interventions, 2016
Coronary drug-eluting stents with biodegradable polymers have been designed to improve safety and... more Coronary drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy. The Scandinavian Organization for Randomized Trials With Clinical Outcome (SORT OUT) VII trial-a large-scale registry-based randomized, multicenter, single-blind, 2-arm, noninferiority trial-compared 2 biodegradable polymer drug-eluting stents: the thin-strut cobalt-chromium sirolimus-eluting Orsiro stent and the stainless steel biolimus-eluting Nobori stent in an all-comer patient population. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 1 year, analyzed by intention to treat (noninferiority margin of 3.0%). Clinically driven event detection based on Danish registries was used. A total of 1261 patients were assigned to receive the sirolimus-eluting stent (1590 lesions) and 1264 patients to the biolimus-eluting stent (1588 lesions). At 1 year, the composite end point target lesion failure occurred in 48 patients (3.8%) in the sirolimus-eluting group and in 58 patients (4.6%) in the biolimus-eluting group (absolute risk difference, -0.78% [upper limit of 1-sided 95% confidence interval, 0.61%]; P<0.0001). Rates of definite stent thrombosis occurred in 5 (0.4%) of the sirolimus-eluting group compared with 15 (1.2%) biolimus-eluting stent-treated patients (rate ratio, 0.33; 95% confidence interval, 0.12-0.92; P=0.034), which largely was attributable to a lower risk of subacute definite stent thrombosis: 0.1% versus 0.6% (rate ratio, 0.12; 95% confidence interval, 0.02-1.00; P=0.05). The thin-strut sirolimus-eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent in unselected patients for target lesion failure at 1 year. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01879358.
The Lancet, 2016
Despite successful treatment of the culprit artery lesion by primary percutaneous coronary interv... more Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI. We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408. Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups. In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population. Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.
American Heart Journal, 2015
In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with prim... more In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PCI) is the preferred treatment. In primary PCI patients with multivessel disease, it is unclear whether culprit vessel PCI only is the preferred treatment. We compared mortality among (1) STEMI patients with single-vessel disease and those with multivessel disease and (2) multivessel disease patients with and without additional revascularization of nonculprit lesions within 2 months after the index PCI. From January 2002 to June 2009, all patients presenting with STEMI and treated with primary PCI were identified from the Western Denmark Heart Registry, which covers a population of 3.0 million. The hazard ratio (HR) for death was estimated using a Cox regression model, controlling for potential confounding. The study cohort consisted of 8,822 patients: 4,770 (54.1%) had single-vessel disease and 4,052 (45.9%) had multivessel disease. Overall, 1-year cumulative mortality was 7.6%, and 7-year cumulative mortality was 24.0%. Multivessel disease was associated with higher 7-year mortality (adjusted HR 1.45 [95% CI 1.30-1.62], P < .001). Among patients with multivessel disease, lack of additional revascularization beyond the culprit lesion was associated with higher 7-year mortality (adjusted HR 1.50 [95% CI 1.25-1.80], P < .001). In patients with multivessel disease who underwent additional revascularization, 7-year mortality (adjusted HR 1.01 [95% CI 0.84-1.22], P = .89) was similar compared to patients with single-vessel disease. In STEMI patients, multivessel disease was associated with a higher mortality compared to single-vessel disease. In multivessel disease patients, additional revascularization was associated with a higher survival compared with culprit vessel PCI only.
Catheterization and Cardiovascular Interventions, 2015
Objective We aimed to compare angiographic and clinical outcomes after the implantation of everol... more Objective We aimed to compare angiographic and clinical outcomes after the implantation of everolimus-eluting (EES) and sirolimus-eluting (SES) stents in patients with diabetes. Background There are limited data on long-term outcome after EES vs SES implantation in diabetic patients. Methods We randomized 213 patients with diabetes and coronary artery disease to EES (n=108) or SES (n=105) implantation. Angiographic follow-up was performed 10 months after the index procedure and all patients were followed clinically for 4 years. The primary endpoint was angiographic in-stent late luminal loss at 10-month follow-up. Secondary endpoints included angiographic restenosis rate, the need for target lesion revascularization (TLR) and major adverse cardiac events (MACE; defined as cardiac death, myocardial infarction, definite stent thrombosis, or TLR) at 4-year follow-up. Results At 10-month angiographic follow-up, in-stent late lumen loss was 0.20 ± 0.53 mm and 0.11 ± 0.49 mm (p=0.28), and angiographic restenosis rate was 3.8% and 5.2% (p=0.72) in the EES and SES groups, respectively. At 4-year clinical follow-up, MACE had occurred in 22 (20.4%) patients in the EES group and 25 (23.8%) patients in SES group (HR 0.84, 95% CI 0.47- 1.49; p=0.55), with TLR performed in 6 (5.6%) and 10 (9.5%) patients in the two groups (HR 0.57, 95% CI 0.21-1-58; p=0.28). Conclusion EES and SES had comparable 10-month angiographic and 4-year clinical outcomes in patients with diabetes mellitus and coronary artery disease. This article is protected by copyright. All rights reserved.
EuroIntervention, 2014
The aim of this substudy of the SORT OUT IV trial was to compare clinical outcomes among patients... more The aim of this substudy of the SORT OUT IV trial was to compare clinical outcomes among patients with acute coronary syndromes (ACS) and stable angina pectoris (SAP) treated with everolimus-eluting stents (EES) or sirolimus-eluting stents (SES). We performed a post hoc subgroup analysis of data from SORT OUT IV. Of 2,705 patients, 1,178 (43.5%) patients had ACS and were treated with EES (n=580) or SES (n=598), and 1,527 (56.5%) patients had SAP and were treated with EES (n=773) or SES (n=754). The primary composite endpoint was major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI), stent thrombosis, or target vessel revascularisation within 18 months. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for the endpoints. At 18-month follow-up, patients with ACS had higher rates of MACE compared to patients with SAP (8.1% versus 6.7%; HR=1.23, 95% CI: 0.93-1.62). MACE did not differ significantly between ACS patients treated with EES or SES (7.3% versus 8.9%; HR=0.81, 95% CI: 0.54-1.22) nor between SAP patients treated with EES or SES (6.9% versus 6.5%; HR=1.05, 95% CI: 0.71-1.55). EES and SES performed similarly with respect to MACE at 18-month follow-up in patients with ACS and SAP.
BMC cardiovascular disorders, 2014
The impact of adherence to the recommended duration of dual antiplatelet therapy after first gene... more The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. We followed 4,154 patients treated with coronary drug-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases. Discontinuation of clopidogrel within the first 3 months after stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were associated with smaller, not statistically significant, increases in MACE rates. Among patients who discontinued clopidogrel, MACE ra...
European Journal of Cardiovascular Medicine, 2010
The present report provides a brief overview of our randomised (12) and registry (13) results wit... more The present report provides a brief overview of our randomised (12) and registry (13) results with ZES and SES in western Denmark. We chose SES as the goldstandard DES based on meta-analyses, (14,15) registry data, (3,16) and randomised trials, (17,18) which have obtained better results with the SES than the PES.
American Heart Journal, 2015
In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocar... more In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, ischemic postconditioning has been shown to reduce infarct size, but the effect on clinical outcome has not been tested in a large randomized trial. In addition, deferring stent implantation in the infarct-related lesion 1 to 3 days after acute opening of the infarct-related artery could have protective effects, by reducing the risk of injury caused by distal embolization and microvascular obstruction. Finally, a considerable fraction of patients present with lesions in other coronary artery branches than the infarct-related artery. Whether a strategy of complete or partial revascularization of these patients should be preferred remains uncertain. The DANAMI 3 trial program was designed to investigate 3 different randomized treatment strategies in patients with ST-segment elevation myocardial infarction: (1) ischemic postconditioning versus conventional treatment with a primary end point of death and hospitalization for heart failure; (2) deferring stent implantation in the infarct-related lesion versus conventional treatment with a primary end point of death, hospitalization for heart failure, reinfarction, and repeat revascularization; and (3) treatment of the culprit lesion only versus fractional flow reserve-guided complete revascularization in patients with multivessel disease, with a primary end point of death, reinfarction, and repeat revascularization. The DANAMI 3 trial program will determine whether either of 2 approaches to reduce reperfusion injury and distal microvascular obstruction with postconditioning or deferred stent implantation will translate into improved clinical outcome and whether patients with multivessel disease undergoing primary percutaneous coronary intervention will benefit from a strategy of complete or partial revascularization.
EuroIntervention, 2011
Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent i... more Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of this study was to use quantitative coronary angiography (QCA) and volumetric intravascular ultrasound (IVUS) to evaluate the effects of the sirolimus-eluting Cypher® stent (SES) and the zotarolimus-eluting Endeavor® stent (ZES) on angiographic late lumen loss and intima hyperplasia in diabetic patients. In the DiabeDES III trial, 127 patients were randomised to SES or ZES stent implantation. Angiographic 10-month follow-up data were available in 105 patients, including 48 SES and 57 ZES treated patients. Angiographic endpoints were in-stent late lumen loss and minimal lumen diameter. IVUS endpoints included NIH volume and in-stent percent volume obstruction. Baseline clinical characteristics and lesion parameters were similar in the two groups. At 10-month follow-up, angiographic in-stent late lumen loss (0.14±0.37 mm vs. 0.74±0.45 mm, p<0.001) was reduced and minimum lumen diameter was higher (2.36±0.53 mm vs. 1.96±0.65, p<0.001) in the SES group as compared to the ZES group. As compared to the ZES group, NIH volume was significantly reduced in the SES group (median [interquartile range]: 0.0 mm3 [0.0 to 1.2] vs. 16.5 mm3 [6.2 to 31.1], p<0.001). In-stent% volume obstruction was significantly reduced in SES as compared to ZES (median [interquartile range]: 0.0% [0.0-0.7] vs. 13.0% [6.7-20.8], p<0.001). In diabetic patients, the SES reduced angiographic late lumen loss and inhibited NIH more effectively than ZES.
EuroIntervention, 2012
In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with prim... more In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PPCI) is the preferred treatment. However, it remains unclear whether the optimal strategy is complete revascularisation or culprit vessel PPCI only. From January 2002 to June 2009 all patients treated with PPCI were identified from the Western Denmark Heart Registry. We examined mortality according to timing of multivessel PCI: acute procedure, staged procedure during the index hospitalisation, or staged procedure performed within 60 days. The hazard ratio (HR) for death was estimated using a time-dependent Cox regression model, with time of PCI for the non-culprit lesion as the time-dependent variable. The study cohort consisted of 5,944 patients, of whom 4,770 (80%) had single-vessel disease and 1,174 (20%) had multivessel PCI within 60 days. Among 354 (30.2%) patients with acute multivessel PCI, 194 (16.5%) patients with multivessel PCI during the index hospitalisation, and 626 (53.3%) patients with multivessel PCI within 60 days after the index hospitalisation, the adjusted HRs for one-year mortality were 1.53 (95% confidence interval (CI): 1.07-2.18), 0.60 (95% CI: 0.28-1.26), and 0.28 (95% CI: 0.14-0.54), respectively, compared to patients with single vessel disease. Acute multivessel PCI in patients with STEMI was associated with increased mortality.
The American Journal of Cardiology, 2014
System delay (delay from emergency medical service call to reperfusion with primary percutaneous ... more System delay (delay from emergency medical service call to reperfusion with primary percutaneous coronary intervention [PPCI]) is acknowledged as a performance measure in ST-elevation myocardial infarction (STEMI), as shorter system delay is associated with lower mortality. It is unknown whether system delay also impacts ability to stay in the labor market. Therefore, the aim of the study was to evaluate whether system delay is associated with duration of absence from work or time to retirement from work among patients with STEMI treated with PPCI. We conducted a population-based cohort study including patients £67 years of age who were admitted with STEMI from January 1, 1999, to December 1, 2011 and treated with PPCI. Data were derived from Danish population-based registries. Only patients who were full-or part-time employed before their STEMI admission were included. Association between system delay and time to return to the labor market was analyzed using a competing-risk regression analysis. Association between system delay and time to retirement from work was analyzed using a Cox regression model. A total of 4,061 patients were included. Ninety-three percent returned to the labor market during 4 years of follow-up, and 41% retired during 8 years of follow-up. After adjustment, system delay >120 minutes was associated with reduced resumption of work (subhazard ratio 0.86, 95% confidence interval 0.81 to 0.92) and earlier retirement from work (hazard ratio 1.21, 95% confidence interval 1.08 to 1.36). In conclusion, system delay was associated with reduced work resumption and earlier retirement. This highlights the value of system delay as a performance measure in treating patients with STEMI. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;114:1810e1816) There is ample evidence that time from first contact with the health care system to initiation of reperfusion therapy (system delay) is associated with mortality in patients with ST-elevation myocardial infarction (STEMI). 1e3 Approximately 45% of all patients admitted with acute myocardial infarction (AMI) are of the working age. 4,5 In 2009, loss in production because of cardiovascular heart disease mortality and morbidity was estimated to cost the European Union around V18 billion, of which about 9% is due to illness among patients of working age. 6 Only few studies have
Clinical Epidemiology, 2014
Lancet, Jan 15, 2015
New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially ... more New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent. This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (more than 50% stenosis) from March, 2011, to August, 2012, were assessed for eligibility. Patients were randomly assigned in a 1:1 ratio to receive either the durable-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a...
JACC. Cardiovascular interventions, 2014
The study sought to compare the risk of late outcome with a focus on very late definite stent thr... more The study sought to compare the risk of late outcome with a focus on very late definite stent thrombosis of the everolimus-eluting stent (EES) with that of the sirolimus-eluting stent (SES) at 3-year follow-up. In the SORT OUT IV (SORT OUT IV Trial), comparing the EES with the SES in patients with coronary artery disease, the EES was noninferior to the SES at 9 months. The SORT OUT IV trial provides long-term head-to-head randomized comparison of the EES with the SES. We prospectively randomized 2,774 patients in the SORT OUT IV trial. Follow-up through 3 years was complete in 2,771 patients (99.9%). The 3-year pre-specified endpoints were composites of safety and efficacy (major adverse cardiac events [MACE]: cardiac death, myocardial infarction, target vessel revascularization, and definite stent thrombosis). At 3 years, the composite endpoint MACE occurred in 9.8% of the EES group and in 11.1% of the SES group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.70 to 1.12)....
The Lancet, 2014
Background In head-to-head comparisons of coronary drug-eluting stents, the primary endpoint is t... more Background In head-to-head comparisons of coronary drug-eluting stents, the primary endpoint is traditionally assessed after 9-12 months. However, the optimum timepoint for this assessment remains unclear. In this study, we assessed clinical outcomes at up to 5 years' follow-up in patients who received two diff erent types of drug-eluting stents.
The Lancet, 2010
Background In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of ... more Background In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the effi cacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who were receiving routine clinical care with no direct follow-up.
The Lancet, 2013
Organization for Randomized Trials with Clinical Outcome (SORT OUT) V investigators (2013). Bioli... more Organization for Randomized Trials with Clinical Outcome (SORT OUT) V investigators (2013). Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V): a randomised non-inferiority trial. Lancet, 381(9867), 661-669.
Journal of the American College of Cardiology, 2010
Journal of the American College of Cardiology, 2012
Background: Diabetes has been associated with an increased risk of peripheral arterial disease (P... more Background: Diabetes has been associated with an increased risk of peripheral arterial disease (PAD) and worse outcomes following treatment. The DEFINITIVE LE study was a global study that assessed the effectiveness of plaque excision using the SilverHawk® and TurboHawkTM systems (Covidien/ev3, Plymouth, MN) for endovascular treatment of PAD in femoropopliteal and tibial-peroneal arteries. Methods: 800 patients with a total of 1023 infrainguinal lesions were enrolled in DEFINITIVE LE and underwent revascularization with plaque excision. Follow-up assessments occurred at pre-discharge, 30 days, 3 months (for patients with RCC 5 or 6), 6 months and 1 year post-procedure. Endpoints were assessed by independent angiographic and duplex core laboratories and adverse events were adjudicated by a Clinical Events Committee. The primary endpoint for claudicants was primary patency (defined using both PSVR Յ 2.4 and PSVR Յ 3.5and estimated by Kaplan-Meier methods). Secondary assessments included change in Rutherford Clinical Category, ankle-brachial index, the Walking Impact Questionnaire, EQ-5D quality of life and adverse events. Results: Preliminary results are shown pending database closure and monitoring; final results will be presented at TCT 2012. The study enrolled 600 subjects (745 lesions) with claudication, 46.7% (280/600) of which had diabetes. Subjects with diabetes differed significantly from those without diabetes in multiple baseline characteristics, but acute and 1-year outcomes were largely similar. Demographics, lesion characteristics and outcomes are shown below.
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Papers by Hans-Henrik Tilsted