BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

The ability of tetraethylene glycol dimethyl ether (tetraglyme) plasma deposited coatings exhibiting ultralow fibrinogen adsorption to reduce blood activation was studied with six in vitro methods, namely fibrinogen and von Willebrand's factor adsorption, total protein adsorption, clotting time in recalcified plasma, platelet adhesion and procoagulant activity, and whole blood thrombosis in a disturbed flow catheter model. Surface plasmon resonance results showed that tetraglyme surfaces strongly resisted the adsorption of all proteins from human plasma. The clotting time in the presence of tetraglyme surfaces was lengthened compared with controls, indicating a lower activation of the intrinsic coagulation cascade. Platelet adhesion and thrombin generation by adherent platelets were greatly reduced on tetraglyme-coated materials, compared with uncoated and Biospan-coated glass slides. In the in vitro disturbed blood flow model, tetraglyme plasma coated catheters had 50% less thrombus than did the uncoated catheters. Tetraglyme-coated materials thus had greatly reduced blood interactions as measured with all six methods. The improved blood compatibility of plasma-deposited tetraglyme is thus not only due to their reduced platelet adhesion and activation, but also to a generalized reduction in blood interactions.

We duplicated the "popcorn effect" of non-contact laser use in vitro. In this model, the technique results in a significant decrease in stone burden (up to 63%) in just 2 minutes. Adequate energy and high frequency seemed to optimize the effectiveness of the method, but excessive energy and frequency produced diminishing returns.

BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

Background The role of preoperative androgen deprivation therapy (ADT) for localized prostate cancer is controversial; prospective assessments have yielded varying results. We sought to define a subset of patients with a higher likelihood of benefit from preoperative ADT. Methods An institutional database including consecutive patients receiving definitive surgery for localized prostate cancer was interrogated. Patients recorded as having received preoperative ADT were matched in a 1:2 fashion to patients who had not received prior ADT. Patients were matched on the basis of clinicopathologic characteristics, use of adjuvant treatment strategies, and duration of PSA follow-up. Time to biochemical recurrence (TTBR) was compared using the Kaplan-Meier method and log-rank test for the overall study population and in subsets defined by D’Amico risk. Results No significant differences in clinicopathologic characteristics were noted between recipients (n=101) and matched non-recipients (n=196) of preoperative ADT. Although not statistically significant, positive surgical margin rates, seminal vesicle invasion and extracapsular extension were less frequent in patients receiving preoperative ADT. Furthermore, a lesser incidence of perioperative complications was noted in this group (7.4% v 18.4%). No significant differences were noted in TTBR between recipients and non-recipients of preoperative ADT in the overall study population. However, amongst patients with high-risk disease, TTBR was significantly longer in those patients who had received preoperative ADT (P=0.004). Conclusions The data presented herein suggest a potential benefit with preoperative ADT in patients with high-risk localized prostate cancer. Consideration should be given to enriching for this subset in preoperative studies of novel endocrine therapies.

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Using color duplex ultrasound (CDU) surveillance of autogenous infrainguinal bypasses, a peak systolic flow velocity (PSFV) ratio of greater than 3 to 1 within the graft relative to adjacent PSFV has been accepted as predicting significant stenosis mandating revision. At the proximal anastomosis, where significant vessel diameter differences and turbulent flow exist, the validity of these criteria is less clear. Our purpose was to review our experience with proximal anastomotic abnormalities in a CDU surveillance protocol. Routine CDU surveillance for all infrainguinal bypass gratis consisted of evaluation in an accredited vascular laboratory at 1 month postoperatively, every 3 months for the first year, every 6 months in the second year, and annually thereafter. Grafts with a PSFV ratio of >3 at the proximal anastomosis on any CDU study were included in this review. From our results we conclude that currently accepted CDU criteria for graft-threatening stenosis may not be valid for abnormalities at the proximal anastomosis of infrainguinal grafts. Regression of these abnormalities is common. Better CDU criteria are needed for predicting not only severity of proximal anastomotic stenosis but also likelihood of graft thrombosis.