Comparative influence of bleeding and ischemic risk factors on diabetic patients undergoing percutaneous coronary intervention with everolimus-eluting stents.

OBJECTIVE: To investigate the impact of ischemic and bleeding risk factors on long-term clinical outcomes of patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) with everolimus-eluting stents. BACKGROUND: Second-generation drug-eluting stents have substantially improved outcomes after PCI in the general population; however, DM patients continue to experience high rates of ischemic and bleeding complications. METHODS: DM patients from the pooled XIENCE V registry were divided into high or low bleeding and ischemic risk groups (HBR, LBR, HIR, and LIR) based on established bleeding (age ≥ 75 years; chronic kidney disease; anemia; prior stroke; oral anticoagulation; thrombocytopenia; prior major bleeding) and ischemic (acute coronary syndrome; prior myocardial infarction [MI]; ≥3 stents implanted; ≥3 vessels treated; ≥3 lesions treated; stent length > 60 mm; bifurcation treated with ≥2 stents; chronic total occlusion) risk factors. The primary outcomes were major adverse cardiac events (MACE; cardiac death, MI, or stent thrombosis) and major bleeding at 4-year follow-up. RESULTS: A total of 3,704 DM patients were divided into four groups (21.5% LBR/LIR; 39.0% LBR/HIR; 15.6% HBR/LIR; 23.9% HBR/HIR). Compared with LBR/LIR patients, those at HBR/HIR and HBR/LIR had a significantly higher risk of MACE (HR (95% CI) 2.7 (1.9-3.9) and 2.2 (1.5-3.2), respectively) and major bleeding (2.7 (1.6-4.8) and 2.6 (1.4-4.7), respectively), while LBR/HIR patients did not. CONCLUSIONS: Among DM patients undergoing PCI, presence of bleeding risk factors was associated with a higher risk of both ischemic and bleeding events, whereas commonly used features of ischemic risk did not impact long-term clinical outcomes.

Efficacy and Safety of the Absorb Bioresorbable Vascular Scaffold in Females and Males: Results of an Individual Patient-Level Pooled Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Because females are under-represented in coronary trials, this study sought to assess the relative safety and efficacy of Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) and the Xience everolimus-eluting stent in females compared with males. BACKGROUND: The Absorb everolimus-eluting BVS provides drug delivery and mechanical support similar to a metallic drug-eluting stent, followed by resorption and restoration of more normal vascular structure with the potential to improve late clinical outcomes. METHODS: The ABSORB II, ABSORB III, ABSORB Japan, and ABSORB China trials were pooled. Baseline clinical, angiography, procedural variables, and 2-year outcomes were analyzed by sex and device. RESULTS: Among 3,384 randomized patients, 932 (27.5%) were female. Females were older, more often had diabetes and hypertension, but had less everolimus-eluting stent, 3-vessel disease, and smoking compared with males (all p≤0.001). The 2-year rates of target lesion failure with BVS versus everolimus-eluting stent in females were 8.9% versus 6.2% (study-level adjusted hazard ratio: 1.47; 95% confidence interval [CI]: 0.88 to 2.46) and 8.9% versus 6.4% in males (HR: 1.40; 95% CI: 1.02 to 1.92; pinteraction = 0.85). There were no significant interactions between sex and device type for any of the components of target lesion failure. CONCLUSIONS: The relative treatment effects of BVS and everolimus-eluting stent for the 2-year rates of target lesion failure and other cardiovascular outcomes were consistent in females and males.

5-year results of a randomized comparison of XIENCE V everolimus-eluting and TAXUS paclitaxel-eluting stents: final results from the SPIRIT III trial (clinical evaluation of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions).

OBJECTIVES: This study sought to evaluate the long-term safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in patients with obstructive coronary artery disease. BACKGROUND: The use of EES compared to PES has been shown to result in improved clinical outcomes in patients undergoing PCI. However, there have been concerns regarding the durability of these benefits over longer-term follow-up. METHODS: SPIRIT III was a prospective, multicenter trial in which 1,002 patients were randomized 2:1 to EES versus PES. Endpoints included ischemia-driven target vessel failure (TVF) (death, myocardial infarction (MI), or ischemia-driven target vessel revascularization [TVR]), the pre-specified primary endpoint), target lesion failure (TLF) (cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization [TLR]), major adverse cardiac events (MACE) (cardiac death, MI, or ischemia-driven TLR), their individual components and stent thrombosis. RESULTS: Five-year follow-up was available in 91.9% of patients. Treatment with EES versus PES resulted in lower 5-year Kaplan-Meier rates of TVF (19.3% vs. 24.5%, p = 0.05), TLF (12.7% vs. 19.0%, p = 0.008), and MACE (13.2% vs. 20.7%, p = 0.007). EES also resulted in reduced rates of all-cause death (5.9% vs. 10.1%, p = 0.02), with nonsignificantly different rates of MI, stent thrombosis, and TLR, and no evidence of late catch-up of TLR over time. CONCLUSIONS: At 5 years after treatment, EES compared to PES resulted in durable benefits in composite safety and efficacy measures as well as all-cause mortality. Additionally, the absolute difference in TLR between devices remained stable over time without deterioration of effect during late follow-up.

Impact of routine angiographic follow-up after percutaneous coronary intervention with drug-eluting stents in the SPIRIT III randomized trial at three years.

Routine angiographic follow-up after bare-metal stent implantation has been associated with an increase in coronary revascularization. The impact of angiographic follow-up after drug-eluting stent placement remains poorly characterized. The prospective, randomized, single-blinded SPIRIT III trial assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were assessed by angiographic versus clinical-only follow-up at 8 months ± 28 days and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564 patients were assigned to angiographic follow-up at 8 months ± 28 days and 438 patients underwent clinical follow-up alone. Three-year major adverse cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased twofold at 9 months, but no difference was noted in ID-TLR for either device. Non-ID-TLR was significantly higher in patients in the angiographic group (4.5% vs 1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007) rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The landmark analysis showed no significant differences between the angiographic and clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In conclusion, routine angiographic follow-up in SPIRIT III did not increase rates of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven revascularization rates with angiographic follow-up of patients with PESs, none of the safety end points were adversely affected.

Side branch occlusion with everolimus-eluting and paclitaxel-eluting stents: three-year results from the SPIRIT III randomised trial.

AIMS AND METHODS: The rates of side branch occlusion and subsequent periprocedural MI during everolimus-eluting stent (EES) and paclitaxel-eluting stent (PES) placement were examined in the randomised SPIRIT III trial. Periprocedural myocardial infarction (MI) following drug-eluting stent placement is associated with long-term adverse outcomes. Occlusion of side branches may be an important factor contributing to periprocedural MIs. Consecutive procedural angiograms of patients randomly assigned to EES (n=669) or PES (n=333) were analysed by an independent angiographic core laboratory. Side branch occlusion was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 or 1. Clinical outcomes through three years were compared by stent type and presence of side branch occlusion. CONCLUSIONS: A total of 2,048 side branches were evaluated (EES N=1,345 side branches in 688 stented lesions, PES N=703 side branches in 346 stented lesions). Patients with compared to those without transient or final side branch occlusion had significantly higher non-Q-wave MI (NQMI) rates in-hospital (9.0% vs. 0.5%, p<0.0001). By multivariable analysis side branch occlusion was an independent predictor of NQMI (OR 4.45; 95% CI [1.82, 10.85]). Transient or final side branch occlusion occurred less frequently in patients receiving EES compared to PES (2.8% vs. 5.2%, p=0.009), contributing to the numerically lower rates of in-hospital NQMI with EES arm compared to PES (0.7% vs. 2.3%, p=0.05). Patients treated with EES rather than PES were less likely to develop side branch occlusion during stent placement, contributing to lower rates of periprocedural MI with EES compared to PES.

Detection of Listeria monocytogenes from a model food by fluorescence resonance energy transfer-based PCR with an asymmetric fluorogenic probe set.

It has been shown that fluorescence resonance energy transfer (FRET)-based PCR, including the TaqMan assay and molecular beacons, has potential for rapid detection of pathogens. In these promising real-time detection assays a single internal oligonucleotide probe labeled on both the 5' (reporter) and 3' (quencher) ends is used for selective generation of fluorescence. In this paper, we describe the use of a previously reported novel probe design for FRET-based PCR detection of Listeria monocytogenes in pure culture and in a model food commodity. In the assay described here an asymmetric probe set is used; this probe set consists of a long 5' fluorescein-labeled reporter probe and a short, complementary 3' DABCYL-labeled quencher oligonucleotide, which are used in a 5' nuclease amplification and detection assay. By using the listeriolysin O (hly) and p60 (iap) genes as amplification targets, the performance of two primer-probe sets in amplification and subsequent detection of target DNA was evaluated. In studies performed with pure cultures of L. monocytogenes, the PCR profiles indicated that the relative change in fluorescence intensity was correlated with both the initial number of cells and the accumulation of specific amplicons for both hly and iap gene fragments. Experiments were also done to determine the applicability of the method to the detection of L. monocytogenes by targeting hly DNA and its short-lived mRNA product in a model food commodity. Twenty-five-milliliter samples of reconstituted nonfat dry milk (NFDM) were seeded with L. monocytogenes and processed to concentrate the bacteria by centrifugation, and this was followed by nucleic acid extraction and amplification with hly-specific primers. Endpoint detection of PCR and reverse transcription-PCR amplicons could be achieved at inoculum levels of 10(3) and 10(4) CFU of L. monocytogenes/25 ml of NFDM, respectively. This study demonstrated that this asymmetric FRET-based amplification and detection protocol provides an alternative approach for endpoint detection of nucleic acid amplification products as applied to detection of pathogens in a model food.