Objectives The aim of this study was to compare the 3-year efficacy and safety of biodegradable polymer with permanent polymer stents and of everolimus-eluting stents (EES) with sirolimus-eluting ...stents (SES). Background Biodegradable polymer drug-eluting stents (DES) offer potential for enhanced late outcomes in comparison with permanent polymer stents. In addition, there is increasing interest in the comparison of EES (Xience, Abbott Vascular, Abbott Park, Illinois) versus SES (Cypher, Cordis Corporation, Miami Lakes, Florida). Methods The ISAR-TEST 4 (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents-4) was a randomized clinical trial with broad inclusion criteria, enrolling 2,603 patients at 2 clinics in Munich, Germany. Patients were randomized to either biodegradable polymer (n = 1,299) or permanent polymer stents (n = 1,304); patients treated with permanent polymer stents were randomly allocated to EES (n = 652) or SES (n = 652). The primary endpoint was the composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization. Results Clinical events continued to accrue at a low rate out to 3 years in all groups. Overall, there was no significant difference between biodegradable polymer and permanent polymer DES with regard to the primary endpoint (20.1% vs. 20.9%, hazard ratio HR: 0.95, 95% confidence interval CI: 0.80 to 1.13; p = 0.59). Rates of definite/probable stent thrombosis were also similar in both groups (1.2% vs. 1.7%, respectively; HR: 0.71, 95% CI: 0.37 to 1.39; p = 0.32). In patients treated with permanent polymer stents, EES were comparable to SES with regard to the primary endpoint (19.6% vs. 22.2%, respectively; HR: 0.87, 95% CI: 0.68 to 1.11; p = 0.26) as well as definite/probable stent thrombosis (1.4% vs. 1.9%, HR: 0.75, 95% CI: 0.32 to 1.78; p = 0.51). Conclusions Biodegradable polymer and permanent polymer DES are associated with similar clinical outcomes at 3 years. In addition, EES are comparable to SES in terms of overall clinical efficacy and safety. (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting STents ISAR-TEST 4: Prospective, Randomized Trial of 3-limus Agent-eluting Stents With Different Polymer Coatings; NCT00598676 )
Background Concern regarding the rate of delayed acute stent thrombosis associated with drug-eluting stent (DES) treatment has resulted in upward revision of the advised duration of dual antiplatelet ...therapy after DES implantation by both European and United States guideline writing committees. In fact, the corroboration of an increased rate of late thrombotic events remains outstanding, and these clinical practice guidelines are limited by an inadequate evidence base on which to ground their recommendations. Hypothesis We postulate that a 6-month duration of clopidogrel therapy after DES implantation is associated with a clinical outcome that is not inferior to that of a 12-month therapy. Study design The I ntracoronary S tenting and A ntithrombotic R egimen: S afety A nd E F ficacy of Six Months Dual Antiplatelet Therapy After Drug- E luting Stenting (ISAR-SAFE) is a multinational, double-blind, placebo-controlled, randomized trial designed to examine the effects of a 6-month duration of clopidogrel therapy after DES implantation compared to that of 12 months. Patients on clopidogrel therapy at 6 months after DES implantation will be randomized in a 1:1 fashion to discontinuation of clopidogrel versus a further 6 months of treatment. The primary end point is a composite of death, myocardial infarction, stent thrombosis, stroke, or thrombolysis in myocardial infarction major bleeding. Clinical follow-up is scheduled at 9 months postrandomization (15 months postintervention). According to power calculations based on a noninferiority design, it is estimated that 6,000 patients are required to be enrolled. Summary There is clinical equipoise on the issue of optimal duration of dual antiplatelet treatment after percutaneous intervention with DES. The ISAR-SAFE trial aims to assess whether discontinuation of clopidogrel 6 months after DES implantation is noninferior to routine prolongation of such therapy out to 1 year.
Summary Background The best way to manage restenosis in patients who have previously received a drug-eluting stent is unknown. We investigated the efficacy of paclitaxel-eluting balloons (PEB), ...paclitaxel-eluting stents (PES), and balloon angioplasty in these patients. Methods In this randomised, open-label trial, we enrolled patients older than 18 years with restenosis of at least 50% after implantation of any limus-eluting stent at three centres in Germany between Aug 3, 2009, and Oct 27, 2011. Patients were randomly assigned (1:1:1; stratified according to centre) to receive PEB, PES, or balloon angioplasty alone by means of sealed, opaque envelopes containing a computer-generated sequence. Patients and investigators were not masked to treatment allocation, but events and angiograms were assessed by individuals who were masked. The primary endpoint was diameter stenosis at follow-up angiography at 6–8 months. Primary analysis was done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00987324. Findings We enrolled 402 patients, of whom 137 (34%) were assigned to PEB, 131 (33%) to PES, and 134 (33%) to balloon angioplasty. Follow-up angiography at 6-8 months was available for 338 (84%) patients. PEB was non-inferior to PES in terms of diameter stenosis (38·0% SD 21·5 vs 37·4% 21·8; difference 0·6%, one-sided 95% CI 4·9%; pnon-inferiority =0·007; non-inferiority margin of 7%). Findings were consistent in per-protocol analysis (pnon-inferiority =0·011). PEB and PES were superior to balloon angioplasty alone (54·1% 25·0; psuperiority <0·0001 for both comparisons). Frequency of death, myocardial infarction, or target lesion thrombosis did not differ between groups. Interpretation By obviating the need for additional stent implantation, PEB could be a useful treatment for patients with restenosis after implantation of a drug-eluting stent. Funding Deutsches Herzzentrum.
Summary Background Comparative assessment of clinical outcomes after use of drug-eluting stents versus bare-metal stents for treatment of aortocoronary saphenous vein graft lesions has not been ...undertaken in large randomised trials. We aimed to undertake a comparison in a randomised trial powered for clinical endpoints. Methods In this randomised superiority trial, patients with de-novo saphenous vein graft lesions were assigned by computer-generated sequence (1:1:1:3) to receive either drug-eluting stents (one of three types: permanent-polymer paclitaxel-eluting stents, permanent-polymer sirolimus-eluting stents, or biodegradable-polymer sirolimus-eluting stents) or bare-metal stents. Randomisation took place immediately after crossing of the lesion with a guidewire, and was stratified for each participating centre. Investigators assessing data were masked to treatment allocation; patients were not masked to allocation. The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularisation at 1 year. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov , number NCT00611910. Findings 610 patients were allocated to treatment groups (303 drug-eluting stent, 307 bare-metal stent). Drug-eluting stents reduced the incidence of the primary endpoint compared with bare-metal stents (44 15% vs 66 22% patients; hazard ratio HR 0·64, 95% CI 0·44–0·94; p=0·02). Target lesion revascularisation rate was reduced by drug-eluting stents (19 7% vs 37 13% patients; HR 0·49, 95% CI 0·28–0·86; p=0·01). No significant differences were seen between drug-eluting stents and bare-metal stents regarding all-cause mortality (15 5% vs 14 5% patients; HR 1·08, 95% CI 0·52–2·24; p=0·83), myocardial infarction (12 4% vs 18 6%; HR 0·66, 95% CI 0·32–1·37; p=0·27), or definite or probable stent thrombosis (2 1% in both groups; HR 1·00, 95% CI 0·14–7·10; p=0·99). Interpretation In patients undergoing percutaneous coronary intervention for de-novo saphenous vein graft lesions, drug-eluting stents are the preferred treatment option because they reduce the risk of adverse events compared with bare-metal stents. Funding Deutsches Herzzentrum.
Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current ...therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.
With the use of in vivo fluorescence microscopy we have analyzed microvascular reperfusion injury of small bowel isograft transplants in rats. Following 1 hr cold storage in University of Wisconsin ...solution, the small bowel was transplanted heterotopically, and the intestinal microcirculation was quantitatively analyzed 20-60 min after onset of reperfusion. The intestinal grafts' capillary perfusion of both the mucosa and the circular and longitudinal muscles was not found altered when compared with the intestinal capillary perfusion of sham-operated controls. In contrast, leukocyte-endothelial cell interaction, including leukocyte rolling (40 +/- 5%) and sticking (280 +/- 100 mm-2) in submucosal postcapillary venules, was significantly increased when compared with nontransplanted controls (12 +/- 8% and 20 +/- 10 mm-2, P < 0.01 and P < 0.05, respectively). Leukocyte-endothelial cell interaction was associated with a marked alteration of lymphatic capillary drainage, as indicated by the low functional density of lymphatic microvessels of 10.2 +/- 6.1 cm-1 (P < 0.01 vs. sham-operated controls (39.2 +/- 6.1 cm-1)). From these results we propose that leukocyte-endothelial cell interaction, not capillary "no-reflow," is the primary step in the manifestation of microvascular reperfusion injury following a short period of cold ischemia in small bowel grafts.
Background: Apart from rejection-related events, the manifestation of ischemia/reperfusion (I/R) injury remains a major problem, hampering success in human small bowel transplantation (SBTx). ...Therefore the aim of this study was to determine the potential of Carolina rinse (CR) to attenuate microvascular reperfusion injury in rat intestinal isografts.
Methods: After 18 hours of cold preservation in 4° C University of Wisconsin solution (UW), rat SBTx was performed. Immediately before reperfusion the intestine was flushed with 4° C or 37° C Ringer's lactate (RL, groups 1 and 2) or CR (groups 3 and 4), respectively. In vivo fluorescence microscopy was used to analyze the grafts' microcirculation.
Results: In group 1 severe microvascular I/R injury was observed in mucosa and muscle layers. Microcirculatory deterioration was paralleled by enhanced leukocyte accumulation in submucosal venules and by impaired subserosal lymphatic capillary drainage (FC
LD). Rinsing the grafts with 37° C RL attenuated leukocyte-endothelial cell interaction and improved subserosal FC
LD; however, it did not affect mucosal microvascular reperfusion damage. In contrast, 4° C CR dramatically improved nutritive perfusion within muscle and mucosa (
p < 0.05) and attenuated leukocyte adherence within submucosal venules (
p < 0.05). Additional prewarming of CR almost completely prevented mucosal I/R injury (
p < 0.05 versus group 3) and caused a fourfold increase of FC
LD.
Conclusions: With this study we demonstrate that CR in combination with rewarming of the graft before reperfusion is an effective regimen to prevent leukocyte accumulation and to counteract microvascular injury after SBTx. (Surgery 1998;123:181-90.)
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