Summary 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 different types of drug-eluting stents. Methods We undertook this multicentre, open-label, randomised superiority trial at five percutaneous coronary intervention centres in Denmark. We randomly allocated 2332 eligible adult patients (≥18 years of age) with an indication for drug-eluting stent implantation to the zotarolimus-eluting Endeavor Sprint stent (Medtronic, Santa Rosa, CA, USA) or the sirolimus-eluting Cypher Select Plus stent (Cordis, Johnson & Johnson, Warren, NJ, USA). Randomisation of participants was achieved by computer-generated block randomisation and a telephone allocation service. The primary endpoint of the SORT OUT III study was a composite of major adverse cardiac events—cardiac death, myocardial infarction, and target vessel revascularisation—at 9 months' follow-up. In this study, endpoints included the occurrence of major adverse cardiac events and definite stent thrombosis at follow-up times of up to 5 years. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00660478. Findings We randomly allocated 1162 patients to receive the zotarolimus-eluting stent and 1170 to the sirolimus-eluting stent. At 5-year follow-up, rates of major adverse cardiac events were similar in patients treated with both types of stents (zotarolimus-eluting stents 197/1162 17·0% vs sirolimus-eluting stents 182/1170 15·6%; odds ratio OR 1·10, 95% CI 0·88–1·37; p=0·40). This finding was indicative of the directly contrasting results for rates of major adverse cardiac events at 1-year follow up (zotarolimus 93/1162 8·0% vs sirolimus 46/1170 3·9%; OR 2·13, 95% CI 1·48–3·07; p<0·0001) compared with those at follow-up between 1 and 5 years (104 9·0% vs 136 11·6%; OR 0·78, 95% CI 0·59–1·02; p=0·071). At 1-year follow-up, definite stent thrombosis was more frequent after implantation of the zotarolimus-eluting stent (13/1162 1·1%) than the sirolimus-eluting stent (4/1170 0·3%; OR 3·34, 95% CI 1·08–10·3; p=0·036), whereas the opposite finding was recorded for between 1 and 5 years' follow-up (zotarolimus-eluting stent 1/1162 0·1% vs sirolimus-eluting stent 21/1170 1·8%, OR 0·05, 95% CI 0·01–0·36; p=0·003). 26 of 88 (30%) target lesion revascularisations in the zotarolimus-eluting stent group occurred between 1 and 5 years' follow-up, whereas 54 of 70 (77%) of those in the sirolimus-eluting stent group occurred during this follow-up period. Interpretation The superiority of sirolimus-eluting stents compared with zotarolimus-eluting stents at 1-year follow-up was lost after 5 years. The traditional 1-year primary endpoint assessment therefore might be insufficient to predict 5-year clinical outcomes in patients treated with coronary drug-eluting stent implantation. Funding Cordis and Medtronic.
Summary Background Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. ...We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. Methods We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov , number NCT01960933. Findings From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004). Interpretation In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. Funding Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.
Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.
Summary Background Third-generation biodegradable polymer drug-eluting stents might reduce the risk of stent thrombosis compared with first-generation permanent polymer drug-eluting stents. We aimed ...to further investigate the effects of a biodegradable polymer biolimus-eluting stent compared with a durable polymer-coated sirolimus-eluting stent in a population-based setting. Methods This randomised, multicentre, all-comer, non-inferiority trial was undertaken at three sites across western Denmark. Eligible patients were aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes, and at least one coronary artery lesion (>50% diameter stenosis). We randomly assigned patients (1:1) using an independently managed computer-generated allocation sequence to receive either a biolimus-eluting biodegradable polymer stent (Nobori, Terumo, Tokyo, Japan) or a sirolimus-eluting permanent polymer stent (Cypher Select Plus, Cordis, Johnson & Johnson, Warren, NJ, USA). The primary endpoint was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularisation) at 9 months, analysed by intention to treat (non-inferiority margin of 0·02). This trial is registered with ClinicalTrials.gov , number NCT01254981. Findings From July, 2009, to January, 2011, we assigned 1229 patients (1532 lesions) to receive the biolimus-eluting stent and 1239 (1555 lesions) to receive the sirolimus-eluting stent. One patient was lost to follow-up because of emigration. Intention-to-treat analysis showed that 50 (4·1%) patients who were assigned the biolimus-eluting stent and 39 (3·1%) who were assigned the sirolimus-eluting stent met the primary endpoint (risk difference 0·9% upper limit of one-sided 95% CI 2·1%; pnon-inferiority =0·06). Significantly more patients in the biolimus-eluting stent group had definite stent thrombosis at 12 months than did those in the sirolimus-eluting stent group (9 0·7% vs 2 0·2%, risk difference 0·6% 95% CI 0·0–1·1; p=0·034). Per-protocol analysis showed that 45 (3·8%) of 1193 patients who received a biolimus-eluting stent and 39 (3·2%) of 1208 who received a sirolimus-eluting stent met the primary endpoint (risk difference 0·5% upper limit of one-sided 95% CI 1·8%; pnon-inferiority =0·03). Interpretation At 1 year follow-up, the biodegradable polymer biolimus-eluting Nobori stent did not improve clinical results compared with a first-generation sirolimus-eluting stent. We will need to obtain long-term data before we can make recommendations for the role of this biolimus-eluting stent in routine clinical practice. Funding Terumo and Cordis (Johnson & Johnson).
Summary Background 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. Methods 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 composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat. The trial was powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent with a predetermined non-inferiority margin of 0·025. This trial is registered with ClinicalTrials.gov , number NCT01956448. Findings Of 7103 screened, 1502 patients with 1883 lesions were assigned to receive the durable-polymer zotarolimus-eluting stent and 1497 patients with 1791 lesions to receive the biodegradable-polymer biolimus-eluting stent. 79 (5·3%) and 75 (5·0%) patients, respectively, met the primary endpoint (absolute risk difference 0·0025, upper limit of one-sided 95% CI 0·016%; p=0·004). The individual components of the primary endpoint did not differ significantly between stent types at 12 months. Interpretation The durable-polymer-coated zotarolimus-eluting stent was non-inferior to the biodegradable-polymer-coated biolimus-eluting stent in unselected patients. Funding Medtronic Cardiovascular and Biosensors Interventional Technologies.
Diabetes is associated with an increased risk of major adverse cardiac events after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus ...treated with the second-generation Endeavor zotarolimus-eluting stent (ZES) or the first-generation Cypher Select+ sirolimus-eluting stent (SES). We randomized 2,332 patients to treatment with ZESs (n = 1,162, n = 169 diabetics) or SESs (n = 1,170, n = 168 diabetics) and followed them for 18 months. Randomization was stratified by presence/absence of diabetes. The primary end point was major adverse cardiac events defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Secondary end points included these individual end points plus all-cause mortality and target lesion revascularization. In diabetic patients, use of ZES compared to SES was associated with an increased risk of major adverse cardiac events (18.3% vs 4.8%, hazard ratio 4.05, 95% confidence interval 1.86 to 8.82), myocardial infarction (4.7% vs 0.6%, hazard ratio 8.09, 95% confidence interval 1.01 to 64.7), target vessel revascularization (14.2% vs 3.0%, hazard ratio 4.99, 95% confidence interval 1.90 to 13.1), and target lesion revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59 to 47.1). In patients without diabetes differences in absolute risk decrease were smaller but similarly favored SES. In conclusion, implantation of ZESs compared to SESs is associated with a considerable increased risk of adverse events in patients with diabetes at 18-month follow-up.
Objectives This study sought to examine the 3-year clinical outcomes in patients treated with the Endeavor (Medtronic, Santa Rosa, California) zotarolimus-eluting stent (ZES) or the Cypher (Cordis, ...Johnson & Johnson, Warren, New Jersey) sirolimus-eluting stent (SES) in routine clinical practice. Background The long-term clinical outcome in patients treated with ZES in comparison with SES is unclear. Methods The authors randomized 2,332 patients to ZES (n = 1,162) or SES (n = 1,170) implantation. Endpoints included major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction, or target vessel revascularization; the individual endpoints of MACE; and definite stent thrombosis. Results At 3-year follow-up, the MACE rate was higher in patients treated with ZES than in patients treated with SES (148 12.9% vs. 116 10.1%; hazard ratio HR: 1.33, 95% confidence interval CI: 1.04 to 1.69; p = 0.022). Target vessel revascularization was more frequent in the ZES group compared with the SES group (103 9.1% vs. 76 6.7%; HR: 1.40, 95% CI: 1.04 to 1.89; p = 0.025), whereas the occurrence of myocardial infarction (3.8% vs. 3.3%) and cardiac death (2.8% vs. 2.8%) did not differ significantly. Although the rate of definite stent thrombosis was similar at 3-year follow-up (1.1% vs. 1.4%), very late (12 to 36 months) definite stent thrombosis occurred in 0 (0%) patients in the ZES group versus 12 (1.1%) patients in the SES group (p = 0.0005). Conclusions Although the 3-year MACE rate is higher in patients treated with ZES versus SES, our data highlight a late safety problem concerning definite stent thrombosis with the use of SES. This finding underscores the importance of long-term follow-up in head-to-head comparisons of drug-eluting stents. (Randomized Clinical Comparison of the Endeavor and the Cypher Coronary Stents in Non-selected Angina Pectoris Patients SORT OUT III; NCT00660478 )
Summary 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 efficacy 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. Methods We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five percutaneous coronary intervention centres between January, 2006, and August, 2007. Computer-generated block randomisation and a telephone allocation service were used to randomly assign patients to receive the zotarolimus-eluting or the sirolimus-eluting stent. Data for follow-up were obtained from national Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial is registered with ClinicalTrials.gov , number NCT00660478. Findings 1162 patients (1619 lesions) were assigned to receive the zotarolimus-eluting stent, and 1170 patients (1611 lesions) to receive the sirolimus-eluting stent. 67 patients (72 lesions) had stent failure, and six patients were lost to follow-up. All randomly assigned patients were included in analyses at 9-month follow-up; 2200 patients (94%) had completed 18-month follow-up by the time of our assessment. At 9 months, the primary endpoint had occurred in a higher proportion of patients treated with the zotarolimus-eluting stent than in those treated with the sirolimus-eluting stent (72 6% vs 34 3%; HR 2·15, 95% CI 1·43–3·23; p=0·0002). At 18-month follow-up, this difference was sustained (113 10% vs 53 5%; 2·19, 1·58–3·04; p<0·0001). For patients receiving the zotarolimus-eluting stent and those receiving the sirolimus-eluting stent, all cause-mortality was similar at 9-month follow-up (25 2% vs 18 2%; 1·40, 0·76–2·56; p=0·28), but was significantly different at 18-month follow-up (51 4% vs 32 3%; 1·61, 1·03–2·50; p=0·035). Interpretation The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care. Funding Cordis and Medtronic.
Objectives This study sought to report the 5-year follow-up results of the Nordic Bifurcation Study. Background Randomized clinical trials with short-term follow-up have indicated that coronary ...bifurcation lesions may be optimally treated using the optional side branch stenting strategy. Methods A total of 413 patients with a coronary bifurcation lesion were randomly assigned to a simple stenting strategy of main vessel (MV) and optional stenting of side branch (SB) or to a complex stenting strategy, namely, stenting of both MV and SB. Results Five-year clinical follow-up data were available for 404 (98%) patients. The combined safety and efficacy endpoint of cardiac death, non–procedure-related myocardial infarction, and target vessel revascularization were seen in 15.8% in the optional SB stenting group as compared to 21.8% in the MV and SB stenting group (p = 0.15). All-cause death was seen in 5.9% versus 10.4% (p = 0.16) and non–procedure-related myocardial infarction in 4% versus 7.9% (p = 0.09) in the optional SB stenting group versus the MV and SB stenting group, respectively. The rates of target vessel revascularization were 13.4% versus 18.3% (p = 0.14) and the rates of definite stent thrombosis were 3% versus 1.5% (p = 0.31) in the optional SB stenting group versus the MV and SB stenting group, respectively. Conclusions At 5-year follow-up in the Nordic Bifurcation Study, the clinical outcomes after simple optional side branch stenting remained at least equal to the more complex strategy of planned stenting of both the main vessel and the side branch.
Objectives The aim of the study was to compare long-term follow-up results of crush versus culotte stent techniques in coronary bifurcation lesions. Background The randomized Nordic Stent Technique ...Study showed similar 6-month clinical and 8-month angiographic results with the crush and culotte stent techniques of de novo coronary artery bifurcation lesions using sirolimus-eluting stents. Here, we report the 36-month efficacy and safety of the Nordic Stent Technique Study. Methods A total of 424 patients with a bifurcation lesion were randomized to stenting of both main vessel and side branch with the crush or the culotte technique and followed for 36 months. Major adverse cardiac events—the composite of cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization—were the primary endpoint. Results Follow-up was complete for all patients. At 36 months, the rates of the primary endpoint were 20.6% versus 16.7% (p = 0.32), index lesion restenosis 11.5% versus 6.5% (p = 0.09), and definite stent thrombosis 1.4% versus 4.7% (p = 0.09) in the crush and the culotte groups, respectively. Conclusions At 36-month follow-up, the clinical outcomes were similar for patients with coronary bifurcation lesions treated with the culotte or the crush stent technique. (Nordic Bifurcation Study. How to Use Drug Eluting Stents DES in Bifurcation Lesions? NCT00376571 )
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