Five-year angiographic, OCT and clinical outcomes of a randomized comparison of everolimus and biolimus-eluting coronary stents with everolimus-eluting bioresorbable vascular scaffolds.

AIMS: To compare 5-year angiographic, optical coherence tomography (OCT), and clinical outcomes between patients treated with bioresorbable vascular scaffolds (BVS) and drug-eluting stents (DES). METHODS: The EverBio-2 trial (Comparison of Everolimus- and Biolimus-Eluting Coronary Stents with Everolimus-Eluting Bioresorbable Vascular Scaffold) was a single-center, assessor-blinded, randomized controlled trial in which 240 patients were randomly allocated (1:1:1) to BVS, everolimus-eluting (EES) or biolimus-eluting (BES) DES. Clinical follow-up was scheduled up to 5 years. All patients, alive and who did not have repeat revascularization of the target lesion during follow-up were asked to return for angiographic follow-up at 5 years. RESULTS: Five-year angiographic follow-up was completed in 122 patients (51%) and OCT analysis was performed in 86 (36%) patients. In-stent late lumen loss was similar in both groups with 0.50 ± 0.38 mm in BVS versus 0.58 ± 0.36 mm in EES/BES, p = 0.20. Clinical follow-up was complete in 232 patients (97%) at 5 years. The rate of the device-oriented endpoint was 22% in the BVS and 18% in the EES/BES group (p = 0.49). The patient-oriented composite endpoint occurred in 40% of BVS- and 43% of EES/BES-treated patients (p = 0.72) at 5 years. No acute coronary syndrome due to stent thrombosis was detected after 2 years. Complete BVS strut resorption was observed at 5 years in the OCT subgroup. CONCLUSION: Five-year clinical outcomes were similar between BVS and DES patients as well as angiographic outcomes in a selected subgroup. However, a definitive conclusion cannot be drawn because the EverBio-2 trial was not powered for clinical and angiographic endpoints at 5 years of follow-up.

Multianalysis with optical coherence tomography and vasomotion in everolimus-eluting stents and everolimus-eluting biovascular scaffolds: the MOVES trial.

Aims: To compare endothelium-dependent vasomotor function and vascular healing 15 months after implantation of two new-generation drug-eluting stents and biovascular scaffolds (BVS). Methods and results: A total of 28 patients previously treated with a SYNERGY stent (bioabsorbable polymer everolimus-eluting stents (BP-EES)), a PROMUS stent (persistent polymer everolimus-eluting stents (PP-EES)) or an ABSORB (BVS) underwent control coronary angiography, 15 months after implantation, coupled with optical coherence tomography imaging and supine bicycle exercise. Intracoronary nitroglycerin was administered after exercise testing. Coronary vasomotor response was assessed using quantitative coronary angiography at rest, during supine bicycle exercise and after nitroglycerin. The primary end point was the percent change in mean lumen diameter compared with baseline. Secondary end points were strut coverage and apposition.There were no significant differences in vasomotor response between the three treatment groups. Patients with PP-EES showed significant vasoconstriction of the proximal peristent segment at maximum exercise (P=0.02). BP-EES (2.7%, 95% CI 0 to 5.5) and BVS (3.2%, 95% CI 0 to 6.7) showed less uncovered struts than PP-EES (12.1%, 95% CI 2.9 to 21.3, P=0.02 and 0.09, respectively). Complete strut apposition was more frequently seen with BP-EES (99.6%, 95% CI 99.2 to 100) than with BVS (98.9%, 95% CI 98.2 to 99.6, P=0.04) or PP-EES (95.0%, 95% CI 91.6 to 98.5, P=0.001). Conclusion: BVS and thin strut BP-EES have a reassuring vasomotion profile, suggesting minimal endothelial dysfunction 15 months after implantation.

Comparison of everolimus- and biolimus-eluting coronary stents with everolimus-eluting bioresorbable vascular scaffolds: Two-year clinical outcomes of the EVERBIO II trial.

BACKGROUND: Data from randomized controlled trials have shown that the ABSORB BVS is non-inferior to Cobalt Chromium everolimus-eluting stents at 2years. METHODS & RESULTS: The EVERBIO II trial (Comparison of Everolimus- and Biolimus-Eluting Coronary Stents with Everolimus-Eluting Bioresorbable Vascular Scaffold) is a single-center, assessor-blind, randomized controlled trial enrolling 240 patients with an allocation ration of 1:1:1 conducted at University and Hospital Fribourg, Switzerland. The studied devices were an everolimus-eluting persistent polymer stent (EES), a biolimus-eluting stent with bioabsorbable polymer (BES) and a fully bioresorbable vascular scaffold (BVS). Clinical end points collected at 9months, 12months, and 2years, were academic research consortium defined composites, device thrombosis and target-vessel revascularization. Clinical follow-up at 2years was available in 96% (N=77) of patients in the EES group, in 100% (N=80) in the BES and 99% (N=77) in the BVS group. The device-oriented composite end point of cardiac death, target-vessel myocardial infarction and target-lesion revascularization occurred in 13 (16%) patients treated with EES, in 7 (9%) patients treated with BES and in 16 (21%) patients treated with BVS. There was no significant difference when the metallic stents were compared to the BVS (p=0.12). There was one late scaffold thrombosis throughout the trial in the BVS group, and no definite stent thrombosis in either EES or BES treated patients. CONCLUSIONS: The current analysis shows no significant differences with regard to clinical outcomes at 2years between BVS and the best-in-class metallic DES. Event rates were numerically higher in BVS-treated patients. However, when BVS were compared to BES alone, the occurrence of device related adverse events was significantly increased.

Mastering Mitral Leaflets Coaptation After Valve Repair with Adjustable Mitral Annuloplasty Ring: Proof of Concept in Mock Loop Study.

This investigation sought to determine the feasibility of a novel mitral ring designed to reshape mitral annulus on beating heart, after surgery. The mitral ring is intended to improve mitral leaflets coaptation to correct residual and recurrent mitral regurgitations. It could also provide progressive correction of mitral regurgitation. The device was tested in ex vivo beating heart model. The novel mitral ring is selectively deformable in P1, P2, and P3 segments using a dedicated angioplasty-type balloon. The deformation should increase leaflets coaptation, reducing distance between the two leaflets. It was implanted using standard surgical techniques. The mock loop is based on passive beating heart. Mitral valve (MV) functioning was evaluated in terms of leaflets coaptation height at P2 level using epicardial echocardiography. The test has been completed on eight swine hearts. Ring size was 30 mm. The balloons were inserted in the connecting line. Each segment of the posterior annulus was independently activated over three progressive positions. Balloon inflation pressures were between 15 and 21 bar. Maximum coaptation height increase was 7 mm. Mean pressure gradient across the MV was 1.7 ± 0.3 mm Hg after complete activation of the device. The device allowed significant increase in coaptation height at P2 level after adjustments at P1, P2, and P3. Results were consistent and reproducible. This feasibility study demonstrates the possibility to reshape the mitral annulus on beating heart to precisely increase MV leaflets coaptation height.

Radiation Exposure of the Operator During Coronary Interventions (from the RADIO Study).

We sought to compare operator radiation exposure during procedures using right femoral access (RFA), right radial access (RRA), and left radial access (LRA) during coronary angiography (CA) and percutaneous coronary intervention (PCI). Because of an increased incidence of long-term malignancy in interventional cardiologists, operator radiation exposure is of rising concern. This prospective study included all consecutive patients who underwent elective or emergency CA ± PCI from September 2014 to March 2015. The primary end point was operator radiation exposure, quantified as the ratio of operator cumulative dose (CD) and patient radiation reported as dose-area product (DAP) (CD/DAP). Secondary end points included CD, DAP, and fluoroscopy time (FT). Overall 830 procedures (457 CA [55%] and 373 PCI [45%]) were performed, 455 (55%) through RFA, 272 (33%) through RRA, and 103 (12%) through LRA. The CD/DAP was lower in RFA (0.09 µSv/Gycm(2) [0.02 to 0.20]) compared with RRA (0.47 µSv/Gycm(2) [0.25 to 0.75], p <0.001). The LRA showed lower CD/DAP compared with RRA (p <0.001). CD was significantly lower in RFA (3 µSv [1 to 7]) compared with RRA (12 µSv [6 to 29], p <0.001). The LRA showed lower CD compared with RRA (p <0.001). There were no significant differences in DAP among the 3 access sites. FT was similar for the 3 groups (RFA 7 ± 7, RRA 5 ± 5, LRA 6 ± 5 minutes, RFA vs RRA: p = 1, RFA vs LRA: p = 0.16, RRA vs LRA: p = 0.52). In conclusion, the use of RFA during CA ± PCI is associated with significantly lower operator radiation exposure compared with RRA. LRA is associated with significantly lower operator radiation exposure compared with RRA.

Vascular response to everolimus- and biolimus-eluting coronary stents versus everolimus-eluting bioresorbable scaffolds--an optical coherence tomography substudy of the EVERBIO II trial.

QUESTIONS UNDER STUDY: Head-to-head optical coherence tomography (OCT) data comparing metallic stents with bioresorbable vascular scaffolds (BVS) are lacking. This study assessed vascular healing at 9-month follow-up after implantation of everolimus- and biolimus-eluting stents (EES; BES) and everolimus-eluting BVS. METHODS: OCT was performed in 74 patients enrolled in the EVERBIO II (NCT01711931) trial (23 with EES: 26 lesions, 7 625 struts; 23 with BES: 26 lesions, 6 140 struts; 28 with BVS: 33 lesions, 10 891 struts). OCT images were acquired using the pullback and nonocclusive flushing technique and analysed offline. RESULTS: BVS demonstrated fewer uncovered struts per patient (12 ± 27 [3.8 ± 8.4%] vs 59 ± 55 [21.8 ± 13.7%] in the EES&BES group, p <0.001), and thicker neointimal hyperplasia (BVS 102 ± 44 µm vs EES&BES 66 ± 36 µm, p <0.01). There was no significant difference with regard to malapposed struts (2.1 ± 2.7% in the BVS vs 4.4 ± 8.8% in the EES&BES group, p = 0.41). In a predefined signal intensity scale, quantitative analysis of the "key component" (black) revealed lower intensity in BVS than EES&BES (14 ± 23% vs 13 ± 12%, p = 0.007). Intensity was lower in polylactide-containing stents (BVS&BES) than in EES (15 ± 19% vs 10 ± 10%, p <0.001). CONCLUSIONS: BVS has fewer uncovered struts and presents with a thicker neointimal coverage compared with EES&BES. It is not known whether this improved capping correlates with superior vascular healing. Polylactide-containing stents (BVS and BES) demonstrate lower peristrut intensity compared with EES.

Comparison of endothelium-dependent and -independent vasomotor response after abluminal biodegradable polymer biolimus-eluting stent and persistent polymer everolimus-eluting stent implantation (COMPARE-IT).

BACKGROUND: Drug-eluting stents (DES) have been associated with local endothelial dysfunction in the segments proximal and distal to the stent (peristent segments) and increased thrombotic risk in long term follow-up. Little data exists on endothelial function post-implantation of new DES with biodegradable polymer. The aim of our study was to compare the local endothelial function assessed by exercise induced coronary vasomotion after implantation of a biolimus A9-eluting stent with biodegradable polymer (BES) with an everolimus-eluting stent with durable polymer (EES). METHODS: Coronary vasomotion was evaluated with quantitative coronary angiography at rest and during supine bicycle exercise in nine patients with EES and thirteen patients with BES, 16 months after stent implantation. Mean luminal diameter of the stent, peristent segments, and of a control vessel were determined at rest, during exercise, and after the administration of nitroglycerine. RESULTS: The control vessel showed exercise-induced vasodilatation in both groups (EES: +6.4±5.5%, p=0.07; BES: +7.8±10.1%, p=0.07). Vasomotion in the stented vessel segment was abolished. There was exercise-induced vasoconstriction in both groups in the segments proximal (EES: -9.6±4.5%; p=0.03; BES: -4.3±5.4%, p=0.02) and distal to the stent (EES: -3.2±9.3%; p=0.41, BES -8.6±8.0%, p<0.01). Sublingual nitroglycerin was associated with maximal vasodilatation of the peristent segments in both groups. CONCLUSION: Alike DES with durable polymer, stents with a biodegradable polymer are associated with exercise-induced paradoxical coronary vasoconstriction of the peristent segments. This data suggests that endothelial dysfunction after DES implantation is not primarily caused by the durability of the polymer coating.

Comparison of everolimus- and biolimus-eluting coronary stents with everolimus-eluting bioresorbable vascular scaffolds.

BACKGROUND: The first CE-approved bioresorbable vascular scaffold (BVS) is effective at treating simple lesions and stable coronary artery disease, but it has yet to be assessed versus the best-in-class drug-eluting stents (DES). OBJECTIVES: This study sought to compare the performance of a BVS with that of everolimus-eluting stents (EES) and biolimus-eluting stents (BES) in all-comer patients. METHODS: The EVERBIO II (Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents II) trial was a single-center, assessor-blinded study of 240 patients randomly assigned in a 1:1:1 ratio to EES, BES, or BVS. The only exclusion criterion was a reference vessel diameter >4.0 mm, which precluded treatment with BVS. The primary endpoint was angiographic late lumen loss (LLL) at 9 months. Secondary endpoints included patient-oriented major acute coronary events (MACE) (death, myocardial infarction [MI], and any revascularization), device-oriented MACE (cardiac death, MI, and target lesion revascularization), and stent thrombosis at the 9-month clinical follow-up. RESULTS: Follow-up angiography was performed in 216 patients (90.7%) at 9 months. In-stent LLL was similar between patients treated with BVS (0.28 ± 0.39 mm) and those treated with EES/BES (0.25 ± 0.36 mm; p = 0.30). Clinical outcomes were similar at 9 months: the patient-oriented MACE rate was 27% in BVS and 26% in the EES/BES group (p = 0.83) and the device-oriented MACE rate was 12% in BVS and 9% in the EES/BES group (p = 0.6). CONCLUSIONS: New-generation metallic DES (EES/BES) were not superior to BVS in terms of angiographic LLL and clinical outcomes. (Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents [EVERBIO II]; NCT01711931).

Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) and contrast-induced acute kidney injury after coronary angiogram.

QUESTIONS UNDER STUDY: Diagnosis of acute kidney injury (AKI) relies on measurement of serum creatinine (SCr). SCr is a late marker of impaired renal function. Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) has given encouraging results for an early and sensitive detection of AKI. This cohort study was conducted (1) to assess the value of uNGAL as early marker of contrast-induced AKI (CI-AKI) in unselected patients undergoing percutaneous coronary procedure (PCP) and (2) to investigate whether uNGAL levels correlate with the volume of contrast medium (CM) used during the procedure. METHODS: We enrolled 244 consecutive adult patients undergoing PCP done with the low-osmolar CM Iomeprolum (median volume of CM 122 [88-168] ml per procedure). uNGAL was measured at its peak with a standardised clinical laboratory platform (ARCHITECT uNGAL assay, Abbott). RESULTS: Overall, the post-PCP uNGAL levels were extremely low in our cohort with a median value of 7.7 [4.0-14.5] ng/ml (N ≤132 ng/ml). Twenty-five (10%) patients developed CI-AKI according to the classical diagnostic criteria (≥25% or ≥44.2 µmol/l increase in SCr) and 8 (3.3%) patients according to the AKIN criteria. Regardless of the definition considered, uNGAL levels did not significantly differ in patients with or without CI-AKI. Similarly, we found no significant correlation between the volume of CM used and the post-PCP uNGAL levels (r = -0.11). CONCLUSIONS: In a large cohort of unselected adult patients, uNGAL measured four to six hours after PCP was ineffective to predict the risk of CI-AKI and did not correlate with the volume of CM used during the procedure.

Long-term comparison of everolimus-eluting and biolimus-eluting stents.

AIMS: Second-generation everolimus-eluting stents (EES) are safer and more efficient than first-generation paclitaxel-eluting stents (PES). Third-generation biolimus-eluting stents (BES) have been found to be non-inferior to PES. To date, there is no available comparative study between EES and BES. We aimed to investigate the safety and efficacy of BES with biodegradable polymer compared to EES with durable polymer at a follow-up of two years in an unselected population of consecutively enrolled patients. METHODS AND RESULTS: A group of 814 consecutive patients undergoing percutaneous coronary intervention (PCI) was enrolled between 2007 and 2010, of which 527 were treated with EES and 287 with BES implantation. Clinical outcome was compared in 200 pairs using propensity score matching. The primary endpoint was a composite of death, myocardial infarction (MI) and target vessel revascularisation (TVR) at two-year follow-up. Median follow-up was 22 months. The primary outcome occurred in 11.5% of EES and 10.5% of BES patients (HR 1.11, 95% CI: 0.61-2.00, p=0.74). At two years, there was no significant difference with regard to death (HR 0.49, 95% CI: 0.18-1.34, p=0.17), cardiac death (HR 0.14, 95% CI: 0.02-1.14, p=0.66) or MI (HR 6.10, 95% CI: 0.73-50.9, p=0.10). Stent thrombosis (ST) incidence was evenly distributed between EES (n=2) and BES (n=2) (p-value=1.0). CONCLUSIONS: This first clinical study failed to demonstrate any significant difference regarding safety or efficacy between these two types and generations of drug-eluting stents (DES).

A randomized comparison of platelet reactivity in patients after treatment with various commercial clopidogrel preparations: the CLO-CLO trial.

BACKGROUND: The salt linked to the clopidogrel molecule in generic preparations is suspected to affect its clinical efficacy. There is a lack of information about inhibition of platelet reactivity by generic preparations. AIMS: To compare the effect of original clopidogrel (clopidogrel bisulphate [Plavix(®)]), generic clopidogrel preparations (clopidogrel hydrochloride [Clopidogrel-Mepha(®)]; clopidogrel besylate [Clopidogrel Sandoz(®)]) and prasugrel (Efient(®)) on platelet reactivity in patients with coronary artery disease. METHODS: Patients with coronary artery disease treated with stents received, in a random sequence, original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate. Platelet function was assessed with the Multiplate analyser after an initial loading dose (600 mg) and at day 10 after each treatment period. Prasugrel was given for another 10 days. An adenosine diphosphate (ADP) test value<46 antiaggregation units (U) was defined as therapeutic platelet inhibition. RESULTS: Sixty patients (mean age 69 ± 10 years; 50 men) were randomized. Original clopidogrel bisulphate, clopidogrel hydrochloride and clopidogrel besylate provided similar inhibition of platelet reactivity with values of 31 ± 25, 33 ± 28 and 28 ± 23 U, respectively (P not significant). Prasugrel provided better inhibition of platelet function (10 ± 11 vs. 31 ± 25 U for clopidogrel bisulphate; P<0.001). An ADP test value>46 U was measured in 11 patients (18%) with clopidogrel bisulphate, 13 (22%) with clopidogrel besylate and 13 (22%) with clopidogrel hydrochloride compared with only one (2%) with prasugrel. CONCLUSION: Generic clopidogrel preparations provided similar inhibition of platelet reactivity to original clopidogrel bisulphate, although prasugrel was more efficient.