Sjoerd H. Hofma

Unrestricted Utilization of Sirolimus-Eluting Stents Compared With Conventional Bare Stent Implantation in the “Real World” The Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Registry

Background—The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown. Methods and Results—Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the R apamycin-E luting S tent E valuated A t R otterdam C ardiology H ospital (RESEARCH) registry. Consecutive patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting stents (SES group) were compared with 450 patients who received bare stents in the period just before (pre-SES group). Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62 [95% CI, 0.44 to 0.89]; P =0.008). The 1-year risk of clinically driven target vessel revascularization in the SES group and in the pre-SES group was 3.7% versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P <0.001). Conclusions—Unrestricted utilization of sirolimus-eluting stents in the “real world” is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation.

Comparison of zotarolimus-eluting and everolimus-eluting coronary stents.

BACKGROUNDnNew-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration.nnnMETHODSnIn this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months.nnnRESULTSnAt least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events.nnnCONCLUSIONSnAt 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)

Clinical, Angiographic, and Procedural Predictors of Angiographic Restenosis After Sirolimus-Eluting Stent Implantation in Complex Patients An Evaluation From the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Study

Background—The factors associated with the occurrence of restenosis after sirolimus-eluting stent (SES) implantation in complex cases are currently unknown. Methods and Results—A cohort of consecutive complex patients treated with SES implantation was selected according to the following criteria: (1) treatment of acute myocardial infarction, (2) treatment of in-stent restenosis, (3) 2.25-mm diameter SES, (4) left main coronary stenting, (5) chronic total occlusion, (6) stented segment >36 mm, and (7) bifurcation stenting. The present study population was composed of 238 patients (441 lesions) for whom 6-month angiographic follow-up data were obtained (70% of eligible patients). Significant clinical, angiographic, and procedural predictors of post-SES restenosis were evaluated. Binary in-segment restenosis was diagnosed in 7.9% of lesions (6.3% in-stent, 0.9% at the proximal edge, 0.7% at the distal edge). The following characteristics were identified as independent multivariate predictors: treatment of in-stent restenosis (OR 4.16, 95% CI 1.63 to 11.01; P <0.01), ostial location (OR 4.84, 95% CI 1.81 to 12.07; P <0.01), diabetes (OR 2.63, 95% CI 1.14 to 6.31; P =0.02), total stented length (per 10-mm increase; OR 1.42, 95% CI 1.21 to 1.68; P <0.01), reference diameter (per 1.0-mm increase; OR 0.46, 95% CI 0.24 to 0.87; P =0.03), and left anterior descending artery (OR 0.30, 95% CI 0.10 to 0.69; P <0.01). Conclusions—Angiographic restenosis after SES implantation in complex patients is an infrequent event, occurring mainly in association with lesion-based characteristics and diabetes mellitus.

Coronary Restenosis After Sirolimus-Eluting Stent Implantation Morphological Description and Mechanistic Analysis From a Consecutive Series of Cases

Background We describe the clinical and morphological patterns of restenosis after sirolimus‐eluting stent (SES) implantation. Methods and Results From 121 patients with coronary angiography obtained >30 days after SES implantation, restenosis (diameter stenosis >50%) was identified in 19 patients and 20 lesions (located at the proximal 5‐mm segment in 30% or within the stent in 70%). Residual dissection after the procedure or balloon trauma outside the stent was identified in 83% of the proximal edge lesions. Lesions within the stent were focal, and stent discontinuity was identified in some lesions evaluated by intravascular ultrasound. Conclusions Sirolimus‐eluting stent edge restenosis is frequently associated with local trauma outside the stent. In‐stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Local conditions instead of intrinsic drug‐resistance to sirolimus are likely to play a major role in post‐SES restenosis. (Circulation. 2003; 108:257‐260.)

Reduction in Thrombotic Events With Heparin-Coated Palmaz-Schatz Stents in Normal Porcine Coronary Arteries.

BACKGROUNDnThe use of stents improves the result after balloon coronary angioplasty. Thrombogenicity of stents is, however, a concern. In the present study, we compared stents with an antithrombotic coating with regular stents.nnnMETHODS AND RESULTSnRegular stents were placed in coronary arteries of pigs receiving no aspirin (group 1; n = 8) or aspirin over 4 weeks (group 2, n = 10) or 12 weeks (group 3, n = 9). Stents coated with heparin (antithrombin III uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group 4). The other animals received aspirin and coated stents with a heparin activity of 12 pmol antithrombin III/stent (group 5, n = 10) or 20 pmol/stent (group 6, n = 10; group 7, n = 10). Quantitative arteriography was performed at implantation and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an additional 5 animals, five regular and five coated stents (20 pmol/stent) were placed and explanted after 5 days for examination of the early responses to the implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups 1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin-coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P < .001). Histological analysis at 4 weeks showed that the neointima in group 6 was thicker compared with its control group 2 (259 +/- 104 and 117 +/- 36 microns, P < .01), but at 12 weeks the thickness was similar (152 +/- 61 and 198 +/- 49 microns, respectively). Comparison at 5 days suggested delayed endothelialization of the coating.nnnCONCLUSIONSnHigh-activity heparin coating of stents eliminates subacute thrombosis in porcine coronary arteries.

Stent fracture and restenosis in the drug-eluting stent era.

Coronary stents, initially reserved for bailout situations, are now used in more than 80% of all cases. However, their efficacy is limited by the occurrence of in-stent restenosis, ranging from 15% to 35% of cases, depending on lesion morphology [1–3]. Recently, drugeluting stents have been proven very effective in suppressing neointimal proliferation and reduced restenosis to single digit numbers [4–6]. We report two cases of treatment failure with sirolimus-eluting stents (SESs) related to stent fractures.

Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries

OBJECTIVEnTo compare percutaneous transluminal coronary angioplasty (PTCA) and stent implantation with respect to the long-term changes they induce in the newly formed endothelium in porcine coronary arteries by studying both morphological and functional parameters of the endothelium at 2 weeks and 3 months after intervention.nnnBACKGROUNDnProblems affecting PTCA or stent implantation have been overcome to a large extent by means of better techniques and the availability of new drugs. Late problems, however, still exist in that restenosis affects a large number of patients. With an increasing number of patients being treated with stents, the problem of in-stent restenosis is of even greater concern, as this seems difficult to treat. A functional endothelial lining is thought to be important in controlling the growth of the underlying vascular tissue. We hypothesized that the enhanced neointimal hyperplasia observed after stenting is associated with a more pronounced and prolonged endothelial dysfunction.nnnMETHODSnArteries were analyzed using a dye-exclusion test and planimetry of permeable areas. Thereafter, the arteries were processed for light and scanning electron microscopy for assessment of morphology and proliferative response.nnnRESULTSnLeakage of the endothelium for molecules such as Evans blue-albumin as well as prolonged endothelial proliferation is observed as late as 3 months after the intervention, and is more pronounced after stenting. Permeability is associated with distinct morphologic characteristics: endothelial retraction, the expression of surface folds, and the adhesion of leukocytes.nnnCONCLUSIONSnStenting especially decreases long-term vascular integrity with respect to permeability and endothelial proliferation, and is associated with distinct morphologic characteristics.

Bioresorbable Scaffolds versus Metallic Stents in Routine PCI

BACKGROUND Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug‐eluting stents in percutaneous coronary intervention (PCI). We performed an investigator‐initiated, randomized trial to compare an everolimus‐eluting bioresorbable scaffold with an everolimus‐eluting metallic stent in the context of routine clinical practice. METHODS We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target‐vessel failure (a composite of cardiac death, target‐vessel myocardial infarction, or target‐vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end‐point events. RESULTS The median follow‐up was 707 days. Target‐vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2‐year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan–Meier estimates in time‐to‐event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2‐year cumulative event rates, 2.0% and 2.7%, respectively), target‐vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2‐year cumulative event rates, 5.5% and 3.2%), and target‐vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2‐year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2‐year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target‐vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow‐up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077.)

Sirolimus-Eluting Stent Implantation in ST-Elevation Acute Myocardial Infarction A Clinical and Angiographic Study

Background—Sirolimus-eluting stents (SES) have recently been proven to reduce restenosis and reintervention compared with bare stents. Safety and effectiveness of SES in acute myocardial infarction remain unknown. Methods and Results—Since April 16, 2002, a policy of routine SES implantation has been instituted in our hospital, with no clinical or anatomic restrictions, as part of the RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry. During 6 months of enrollment, 96 patients with ST-elevation acute myocardial infarction underwent percutaneous recanalization and SES implantation; these patients comprise the study population. The incidence of major adverse cardiac events (death, nonfatal myocardial infarction, reintervention) was evaluated. Six-month angiographic follow-up was scheduled per protocol. At baseline, diabetes mellitus was present in 12.5% and multivessel disease in 46.9%. Primary angioplasty was performed in 89 patients (92.7%). Infarct location was anterior in 41 (42.7%) of the cases, and 12 patients (12.5%) had cardiogenic shock. Postprocedural TIMI-3 flow was achieved in 93.3% of the cases. In-hospital mortality was 6.2%. One patient (1.1%) had reinfarction and target lesion reintervention the first day as a result of distal dissection and acute vessel occlusion. During follow-up (mean follow-up of 218±75 days), 1 patient died (1.1%), no patient had recurrent myocardial infarction, and there were no additional reinterventions. No early or late stent thromboses were documented. At angiographic follow-up (70%), late loss was −0.04±0.25, and no patient presented angiographic restenosis. Conclusions—In this study, sirolimus-eluting stent implantation for patients with ST-elevation acute myocardial infarction was safe without documented angiographic restenosis at 6 months.

Everolimus-eluting bioresorbable stent vs. durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction: results of the randomized ABSORB ST-segment elevation myocardial infarction-TROFI II trial.

Abstract Aims Patients with ST-segment elevation myocardial infarction (STEMI) feature thrombus-rich lesions with large necrotic core, which are usually associated with delayed arterial healing and impaired stent-related outcomes. The use of bioresorbable vascular scaffolds (Absorb) has the potential to overcome these limitations owing to restoration of native vessel lumen and physiology at long term. The purpose of this randomized trial was to compare the arterial healing response at short term, as a surrogate for safety and efficacy, between the Absorb and the metallic everolimus-eluting stent (EES) in patients with STEMI. Methods and results ABSORB-STEMI TROFI II was a multicentre, single-blind, non-inferiority, randomized controlled trial. Patients with STEMI who underwent primary percutaneous coronary intervention were randomly allocated 1:1 to treatment with the Absorb or EES. The primary endpoint was the 6-month optical frequency domain imaging healing score (HS) based on the presence of uncovered and/or malapposed stent struts and intraluminal filling defects. Main secondary endpoint included the device-oriented composite endpoint (DOCE) according to the Academic Research Consortium definition. Between 06 January 2014 and 21 September 2014, 191 patients (Absorb [n = 95] or EES [n = 96]; mean age 58.6 years old; 17.8% females) were enrolled at eight centres. At 6 months, HS was lower in the Absorb arm when compared with EES arm [1.74 (2.39) vs. 2.80 (4.44); difference (90% CI) −1.06 (−1.96, −0.16); Pnon-inferiority <0.001]. Device-oriented composite endpoint was also comparably low between groups (1.1% Absorb vs. 0% EES). One case of definite subacute stent thrombosis occurred in the Absorb arm (1.1% vs. 0% EES; P = ns). Conclusion Stenting of culprit lesions with Absorb in the setting of STEMI resulted in a nearly complete arterial healing which was comparable with that of metallic EES at 6 months. These findings provide the basis for further exploration in clinically oriented outcome trials.