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Objectives: We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents. Background: Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans. Methods: Venous blood samples in a subset of 39 patients were drawn just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method. Results: The total dose of everolimus received by the patients ranged from 53 to 588 μg. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T max values ranged from 0.13 and 2.17 hours; individual C max ranged from 0.14 to 2.79 ng/mL. Conclusion: This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely. [Copyright &y& Elsevier]

Background: The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents.Methods: We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up.Results: At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002).Conclusions: In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target-vessel failure, myocardial infarction, stent thrombosis, and target-vessel revascularization at 1 year. (Funded by Boston Scientific; TUXEDO-India Clinical Trials Registry-India number, CTRI/2011/06/001830). [ABSTRACT FROM AUTHOR]

Background: Procedural technique may affect clinical outcomes after bioresorbable vascular scaffold (BVS) implantation. Prior studies suggesting such a relationship have not adjusted for baseline patient and lesion characteristics that may have influenced operator choice of technique and outcomes.Objectives: This study sought to determine whether target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) and scaffold thrombosis (ScT) rates within 3 years of BVS implantation are affected by operator technique (vessel size selection and pre- and post-dilation parameters).Methods: TLF and ScT rates were determined in 2,973 patients with 3,149 BVS-treated coronary artery lesions from 5 prospective studies (ABSORB II, ABSORB China, ABSORB Japan, ABSORB III, and ABSORB Extend). Outcomes through 3 years (and between 0 to 1 and 1 to 3 years) were assessed according to pre-specified definitions of optimal technique (pre-dilation, vessel sizing, and post-dilation). Multivariable analysis was used to adjust for differences in up to 18 patient and lesion characteristics.Results: Optimal pre-dilation (balloon to core laboratory-derived reference vessel diameter ratio ≥1:1), vessel size selection (reference vessel diameter ≥2.25 mm and ≤3.75 mm), and post-dilation (with a noncompliant balloon at ≥18 atm and larger than the nominal scaffold diameter, but not by >0.5 mm larger) in all BVS-treated lesions were performed in 59.2%, 81.6%, and 12.4% of patients, respectively. BVS implantation in properly sized vessels was an independent predictor of freedom from TLF through 1 year (hazard ratio [HR]: 0.67; p = 0.01) and through 3 years (HR: 0.72; p = 0.01), and of freedom from ScT through 1 year (HR: 0.36; p = 0.004). Aggressive pre-dilation was an independent predictor of freedom from ScT between 1 and 3 years (HR: 0.44; p = 0.03), and optimal post-dilation was an independent predictor of freedom from TLF between 1 and 3 years (HR: 0.55; p = 0.05).Conclusions: In the present large-scale analysis from the major ABSORB studies, after multivariable adjustment for baseline patient and lesion characteristics, vessel sizing and operator technique were strongly associated with BVS-related outcomes during 3-year follow-up. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281; ABSORB III Randomized Controlled Trial [RCT] [ABSORB-III]; NCT01751906; A Clinical Evaluation of Absorb Bioresorbable Vascular Scaffold [Absorb BVS] System in Chinese Population-ABSORB CHINA Randomized Controlled Trial [RCT] [ABSORB CHINA]; NCT01923740; ABSORB EXTEND Clinical Investigation [ABSORB EXTEND]; NCT01023789; AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284). [ABSTRACT FROM AUTHOR]