Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis

BACKGROUND: Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. METHODS AND RESULTS: The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020+/-283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2+/-2.4 mm(2) and evidence of vessel remodeling (index, 1.6+/-0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263+/-149 white blood cells per high-power field) and eosinophils (DES, 20+/-24 eosinophils per high-power field; sirolimus-eluting stents, 34+/-28; paclitaxel-eluting stents, 6+/-6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20+/-24) than in those from spontaneous acute myocardial infarction (7+/-10), early bare-metal stent ST (1+/-1), early DES ST (1+/-2), and late bare-metal stent ST (2+/-3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm(2) increase in ISA cross-sectional area. CONCLUSIONS: Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition.

Long-term outcomes of patients receiving zotarolimus-eluting stents in ST elevation myocardial infarction, non-ST elevation acute coronary syndrome, and stable angina: data from the Resolute program

BACKGROUND Outcome data are limited in patients with ST-segment elevation acute myocardial infarction (STEMI) or other acute coronary syndromes (ACSs) who receive a drug-eluting stent (DES). Data suggest that first generation DES is associated with an increased risk of stent thrombosis when used in STEMI. Whether this observation persists with newer generation DES is unknown. The study objective was to analyze the two-year safety and effectiveness of Resolute™ zotarolimus-eluting stents (R-ZESs) implanted for STEMI, ACS without ST segment elevation (non-STEACS), and stable angina (SA). METHODS Data from the Resolute program (Resolute All Comers and Resolute International) were pooled and patients with R-ZES implantation were categorized by indication: STEMI (n=335), non-STEACS (n=1416), and SA (n=1260). RESULTS Mean age was 59.8±11.3 years (STEMI), 63.8±11.6 (non-STEACS), and 64.9±10.1 (SA). Fewer STEMI patients had diabetes (19.1% vs. 28.5% vs. 29.2%; P<0.001), prior MI (11.3% vs. 27.2% vs. 29.4%; P<0.001), or previous revascularization (11.3% vs. 27.9% vs. 37.6%; P<0.001). Two-year definite/probable stent thrombosis occurred in 2.4% (STEMI), 1.2% (non-STEACS) and 1.1% (SA) of patients with late/very late stent thrombosis (days 31-720) rates of 0.6% (STEMI and non-STEACS) and 0.4% (SA) (P=NS). The two-year mortality rate was 2.1% (STEMI), 4.8% (non-STEACS) and 3.7% (SA) (P=NS). Death or target vessel re-infarction occurred in 3.9% (STEMI), 8.7% (non-STEACS) and 7.3% (SA) (P=0.012). CONCLUSION R-ZES in STEMI and in other clinical presentations is effective and safe. Long term outcomes are favorable with an extremely rare incidence of late and very late stent thrombosis following R-ZES implantation across indications.

Comparison of everolimus- and biolimus-eluting stents with everolimus-eluting bioresorbable vascular scaffold stents: study protocol of the randomized controlled EVERBIO II

BACKGROUND: Second-generation everolimus-eluting stents (EES) and third generation biolimus-eluting stents (BES) have been shown to be superior to first-generation paclitaxel-eluting stents (PES) and second-generation sirolimus-eluting stents (SES). However, neointimal proliferation and very late stent thrombosis is still an unresolved issue of drug-eluting stent (DES) implantation overall. The Absorb™ (Abbott Vascular, Abbott Park, IL, USA) is the first CE approved DES with a bioresorbable vascular scaffold (BVS) thought to reduce long-term complication rates. The EVERBIO II trial was set up to compare the BVS safety and efficacy with both EES and BES in all patients viable for inclusion. METHODS/DESIGN: The EVERBIO II trial is a single-center, assessor-blinded, randomized trial. The study population consists of all patients aged≥18 years old undergoing percutaneous coronary intervention. Exclusion criterion is where the lesion cannot be treated with BVS (reference vessel diameter>4.0 mm). A total of 240 patients will be enrolled and randomly assigned into 3 groups of 80 with either BVS, EES or BES implantation. All patients will undergo a follow-up angiography study at 9 months. Clinical follow-up for up to 5 years will be conducted by telephone. The primary endpoint is in-segment late lumen loss at 9 months measured by quantitative coronary angiography. Secondary endpoints are patient-oriented major adverse cardiac event (MACE) (death, myocardial infarction and target-vessel revascularization), device-oriented MACE (cardiac death, myocardial infarction and target-lesion revascularization), stent thrombosis according to ARC and binary restenosis at follow-up 12 months angiography. DISCUSSION: EVERBIO II is an independent, randomized study, aiming to compare the clinical efficacy, angiographic outcomes and safety of BVS, EES and BES in all comer patients. TRIAL REGISTRATION: The trial listed in clinicaltrials.gov as NCT01711931.

Comparison of zotarolimus- and everolimus-eluting coronary stents: final 5-year report of the RESOLUTE all-comers trial

BACKGROUND Newer-generation drug-eluting stents that release zotarolimus or everolimus have been shown to be superior to the first-generation drug-eluting stents. However, data comparing long-term safety and efficacy of zotarolimus- (ZES) and everolimus-eluting stents (EES) are limited. RESOLUTE all-comers (Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) trial compared these 2 stents and has shown that ZES was noninferior to EES at 12-month for the primary end point of target lesion failure. We report the secondary clinical outcomes at the final 5-year follow-up of this trial. METHODS AND RESULTS RESOLUTE all-comer clinical study is a prospective, multicentre, randomized, 2-arm, open-label, noninferiority trial with minimal exclusion criteria. Patients (n=2292) were randomly assigned to treatment with either ZES (n=1140) or EES (n=1152). Patient-oriented composite end point (combination of all-cause mortality, myocardial infarction, and any revascularizations), device-oriented composite end point (combination of cardiac death, target vessel myocardial infarction, and clinically indicated target lesion revascularization), and major adverse cardiac events (combination of all-cause death, all myocardial infarction, emergent coronary bypass surgery, or clinically indicated target lesion revascularization) were analyzed at 5-year follow-up. The 2 groups were well-matched at baseline. Five-year follow-up data were available for 98% patients. There were no differences in patient-oriented composite end point (ZES 35.3% versus EES 32.0%, P=0.11), device-oriented composite end point (ZES 17.0% versus EES 16.2%, P=0.61), major adverse cardiac events (ZES 21.9% versus EES 21.6%, P=0.88), and definite/probable stent thrombosis (ZES 2.8% versus EES 1.8%, P=0.12). CONCLUSIONS At 5-year follow-up, ZES and EES had similar efficacy and safety in a population of patients who had minimal exclusion criteria. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00617084.

Impact of body mass index on long-term clinical outcomes after second-generation drug eluting stent implantation: Insights from the international global RESOLUTE program

BACKGROUND An increased body mass index (BMI) is associated with a high risk of cardiovascular disease and reduction in life expectancy. However, several studies reported improved clinical outcomes in obese patients treated for cardiovascular diseases. The aim of the present study is to investigate the impact of BMI on long-term clinical outcomes after implantation of zotarolimus eluting stents. METHODS Individual patient data were pooled from the RESOLUTE Clinical Program comprising five trials worldwide. The study population was sorted according to BMI tertiles and clinical outcomes were evaluated at 2-year follow-up. RESULTS Data from a total of 5,127 patients receiving the R-ZES were included in the present study. BMI tertiles were as follow: I tertile (≤ 25.95 kg/m(2) -Low or normal weight) 1,727 patients; II tertile (>25.95 ≤ 29.74 kg/m(2) -overweight) 1,695 patients, and III tertile (>29.74 kg/m(2) -obese) 1,705 patients. At 2-years follow-up no difference was found for patients with high BMI (III tertile) compared with patients with normal or low BMI (I tertile) in terms of target lesion failure (I-III tertile, HR [95% CI] = 0.89 [0.69, 1.14], P = 0.341; major adverse cardiac events (I-III tertile, HR [95% CI] = 0.90 [0.72, 1.14], P = 0.389; cardiac death (I-III tertile, HR [95% CI] = 1.20 [0.73, 1.99], P = 0.476); myocardial infarction (I-III tertile, HR [95% CI] = 0.86 [0.55, 1.35], P = 0.509; clinically-driven target lesion revascularization (I-III tertile, HR [95% CI] = 0.75 [0.53, 1.08], P = 0.123; definite or probable stent thrombosis (I-III tertile, HR [95% CI] = 0.98 [0.49, 1.99], P = 0.964. CONCLUSIONS In the present study, the patients' body mass index was found to have no impact on long-term clinical outcomes after coronary artery interventions.

A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus: The RESERVOIR Clinical Trial.

OBJECTIVES The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM). BACKGROUND The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM. METHODS This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up. RESULTS A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group. CONCLUSIONS AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Acute Eosinophilic and Neutrophilic Pneumonia following Transarterial Chemoembolization with Drug-Eluting Beads Loaded with Doxorubicin for Hepatocellular Carcinoma: A Case Report.

At an intermediate or advanced stage, i.e. stage B or C, based on the Barcelona Clinic Liver Cancer classification of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) may be offered as a treatment of palliative intent. We report the case of a patient suffering from acute respiratory distress syndrome after TACE with drug-eluting beads loaded with doxorubicin for HCC. To our knowledge, this is the first case described where a bronchoalveolar lavage was performed, and where significant levels of alveolar eosinophilia and neutrophilia were evident, attributed to a pulmonary toxicity of doxorubicin following liver chemoembolization. © 2014 S. Karger AG, Basel.

Avaliação da endotelização de hastes de stents em artérias ilíacas de coelhos

FUNDAMENTO: A rápida endotelização pós-implante de stent é ocorrência desejável por teoricamente reduzir a possibilidade de trombose do stent. OBJETIVO: Avaliar a extensão da endotelização de hastes de stents eluidores de sirolimus (liberados da face luminal e abluminal e abluminal exclusivamente) em artérias ilíacas de coelhos. MÉTODOS: Foram implantados em artérias ilíacas de 10 coelhos quatro stents eluidores de sirolimus na face luminal e abluminal, três stents eluidores de sirolimus na face abluminal, seis stents recobertos com polímero e quatro stents sem recobrimento. Após quatro semanas, foi realizada eutanásia e utilizou-se microscopia eletrônica de varredura para quantificação da área de hastes de stent exposta e da porcentagem de endotelização. RESULTADOS: A área (média ± DP) (mm²) de hastes expostas de stent sem recobrimento, stent recoberto com polímero, stent eluidor de sirolimus na face luminal e abluminal e stent eluidor de sirolimus na face abluminal foi de 0,12 ± 0,08; 0,09 ± 0,12; 0,60 ± 0,67 e 0,05 ± 0,04 respectivamente (p = 0,120). A porcentagem de endotelização (média ± DP) (%) de stent sem recobrimento, stent recoberto com polímero, stent eluidor de sirolimus na face luminal e abluminal e stent eluidor de sirolimus na face abluminal foi de 99 ± 01; 99 ± 0; 97 ± 03 e 99 ± 0 respectivamente (p = 0,133). CONCLUSÃO: Após quatro semanas de implante em artérias ilíacas de coelhos, os stents com liberação de sirolimus tanto da face luminal e abluminal quanto da face abluminal exclusivamente apresentaram taxas de endotelização de hastes de stent semelhantes aos apresentados nos demais tipos de stents sem eluição de medicamento.

The impact of body mass index on the one year outcomes of patients treated by percutaneous coronary intervention with Biolimus- and Sirolimus-eluting stents (from the LEADERS Trial)

The aim of this analysis was to assess the effect of body mass index (BMI) on 1-year outcomes in patients enrolled in a contemporary percutaneous coronary intervention trial comparing a sirolimus-eluting stent with a durable polymer to a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients who underwent percutaneous coronary intervention were randomized to treatment with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n = 850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 1 year, the incidence of the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was assessed. In addition, rates of clinically justified target lesion revascularization and stent thrombosis were assessed. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 1-year mortality. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was significantly higher in the obese group (8.7% in normal-weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent predictor of stent thrombosis. Stent type had no impact on the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95% confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an independent predictor of major adverse cardiac events at 1-year clinical follow-up. The higher incidence of stent thrombosis in the obese group may suggest the need for a weight-adjusted dose of clopidogrel.

Pooled analysis of trials comparing titanium-nitride-oxide-coated stents with paclitaxel-eluting stents in patients undergoing coronary stenting

We performed a pooled analysis of three trials comparing titanium-nitride-oxide-coated bioactive stents (BAS) with paclitaxel-eluting stents (PES) in 1,774 patients. All patients were followed for 12 months. The primary outcomes of interest were recurrent myocardial infarction (MI), death and target lesion revascularization (TLR). Secondary endpoints were stent thrombosis (ST) and major adverse cardiac events (MACE) including MI, death and TLR. There were 922 patients in the BAS group and 852 in the PES group. BAS significantly reduced the risk of recurrent MI (2.7% vs. 5.6%; risk ratio 0.50, 95% CI 0.31-0.81; p = 0.004) and MACE (8.9% vs. 12.6%; risk ratio 0.71, 95% CI 0.54-0.94; p = 0.02) during the 12 months of follow up. In contrast, the differences between BAS and PES were not statistically significant with respect to TLR (risk ratio 0.98, 95% CI 0.68-1.41), death (risk ratio 0.96, 95% CI 0.61-1.51) and definite ST (risk ratio 0.28, 95% CI 0.05-1.47). In conclusion, the results of this analysis suggest that BAS is effective in reducing TLR and improves clinical outcomes by reducing MI and MACE compared with PES.

Long-term comparison of everolimus-eluting and sirolimus-eluting stents for coronary revascularization

Objectives This study sought to compare the unrestricted use of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention. Background It is unclear whether there are differences in safety and efficacy between EES and SES during long-term follow-up. Methods Using propensity score matching, clinical outcome was compared among 1,342 propensity score–matched pairs of patients treated with EES and SES. The primary outcome was a composite of death, MI, and target vessel revascularization. Results The median follow-up was 1.5 years with a maximum of 3 years. The primary outcome occurred in 14.9% of EES- and 18.0% of SES-treated patients up to 3 years (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.68 to 1.00, p = 0.056). All-cause mortality (6.0% vs. 6.5%, HR: 0.92, 95% CI: 0.68 to 1.25, p = 0.59) was similar, risks of myocardial infarction (MI) (3.3% vs. 5.0%, HR: 0.62, 95% CI: 0.42 to 0.92, p = 0.017), and target vessel revascularization (7.0% vs. 9.6%, HR: 0.75, 95% CI: 0.57 to 0.99, p = 0.039) were lower with EES than SES. Definite stent thrombosis (ST) (HR: 0.30, 95% CI: 0.12 to 0.75, p = 0.01) was less frequent among patients treated with EES. The reduced rate of MI with EES was explained in part by the lower risk of definite ST and the corresponding decrease in events associated with ST (HR: 0.25, 95% CI: 0.08 to 0.75, p = 0.013). Conclusions The unrestricted use of EES appears to be associated with improved clinical long-term outcome compared with SES. Differences in favor of EES are driven in part by a lower risk of MI associated with ST.

Head-to-head comparison of the neointimal response between metallic and bioresorbable everolimus-eluting scaffolds using optical coherence tomography

This study sought to compare the neointimal response of metallic everolimus drug-eluting stents (DES) and polymeric everolimus bioresorbable vascular scaffolds (BVS) by optical coherence tomography at 1 year.