bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis comparing impact of age, sex and renal function on the efficacy and safety of new oral anticoagulants vs. vitamin K antagonists for the treatment of acute venous thromboembolisms
Authors: She J , Zhuo B.Z 
Published: November 2020

Abstract

Background
New direct oral anticoagulants (NOACs), as a preferable treatment option for acute venous thromboembolism (VTE) have been recommended with practical advantages as compared to Vitamin K antagonists (VKAs) in clinical practice.

Purpose
In our study, we performed a meta-analysis to determine the efficacy and safety of NOACs vs. VKAs in patients with different age, sex and renal function for the treatment of VTE.

Methods
Electronic databases (accessed October 2019) were systematically searched to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban versus VKAs for the treatment of acute venous thromboembolism.

Results
NOACs was associated with a borderline higher efficacy in female (OR 0.79, 95% CI 0.62–1.02), and a significantly higher efficacy in patients with age more than 75 (OR 0.51, 95% CI 0.32–0.80) and creatinine clearance less than 50 mL/min (OR 0.57, 95% CI 0.32–0.99). NOACs also show advantage in terms of major or clinically relevant non-major bleeding in male (OR 0.72, 95% CI 0.60–0.86), and patients with creatinine clearance more than 50 mL/min (OR 0.75, 95% CI 0.67–0.84).

Conclusions
NOACs have exhibited clinical preference among patients with acute VTE as compared to VKA with significantly decreased thrombosis events and lower bleeding complications, especially in patients with age more than 75 and creatinine clearance less than 50 mL/min.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): This study was supported by the National Natural Science Foundation of China (81800390) and the Natural Science Foundation of Shaanxi province (2018KW067).
Effects of PCSK9 inhibitor on adverse limb outcomes in patients with critical limb ischemia
Authors: Sato Y , Uzui H , Aiki Y , Aoyama D , Yamaguchi J , Nodera M , Shiomi Y , Hasegawa K , Ikeda H , Tama N , Fukuoka Y , Morishita T , Ishida K , Miyazaki S , Tada H 
Published: November 2020

Abstract

Background
The proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-I), evolocumab, reduced the risk of cardiovascular event in patients with peripheral artery disease in FOURIER trial. However, the effects of evolocumab on favorable limb outcomes in patients with critical limb ischemia (CLI) is still unclear.

Purpose
The aim of this study was to evaluate the impacts of evolocumab on favorable limb outcomes and lipid profile in patients with CLI.

Methods
This was a single center, prospective observational study. A total of 39 patients with CLI were enrolled between November 2016 to May 2019. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated group: E group (mean 69.4±11.7 years, n=14) and evolocumab non-treated group: Non-E group (mean 74.0±8.8 years, n=25). Baseline characteristics were assessed at admission. Lipid profile was evaluated at admission, 1, 3, 6, 12 and 18 months. The primary outcome was defined 18-month amputation-free survival (AFS). The secondary outcomes were defined 18-month overall survival (OS) and wound-free limb salvage. Mean follow-up period was 18±11 months.

Results
The patients in E group had greater reduction in levels of LDL cholesterol and non-HDL cholesterol than those in Non-E group over time. The reduction in MDA-LDL level was maintained at 1, 3, 6, 12 months, respectively. The 18-month AFS rate in the E-group was significantly higher than those in the Non-E group (log-rank p=0.02). The patients receiving evolocumab had a lower hazard regarding AFS (hazard ratio, 0.12; 95% confidence interval, 0.02–0.94; P=0.043) and a higher proportion of wound-free limb salvage at 12 months (E group [92%] vs Non-E group [57%], P=0.034) and 18 months (92% vs 52%, P=0.03). Otherwise, evolocumab administration was not associated with 18-month OS (log-rank p=0.053).

Conclusions
Evolocumab administration may be associated with the favorable outcome of 18-month AFS in the patients with CLI. Additionally, long-term administration of evolocumab over 12 months may improve wound-free limb salvage.
Effects of evolocumab on limb outcomes

Funding Acknowledgement
Type of funding source: None
Sodium-glucose cotransporter-2 inhibitors and their combination with glucagon like peptide-1 receptor agonists improve endothelial glycocalyx and arterial stiffness in type-2 diabetes
Authors: Ikonomidis I , Pavlidis G , Thymis J , Birba D , Kalogeris A , Kousathana F , Kountouri A , Balampanis K , Parissis J , Andreadou I , Katogiannis K , Dimitriadis G , Bamias A , Iliodromitis E , Lambadiari V 
Published: November 2020

Abstract

Background/Introduction
Type-2 diabetes mellitus (T2DM) is associated with endothelial and arterial dysfunction.

Purpose
We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i)and their combination on endothelial and arterial function of T2DM patients.

Methods
A hundred-sixty T2DM patients (age: 58±10 years) were randomized to insulin (n=40), liraglutide (n=40), empagliflozin (n=40) or their combination (GLP-1RA+SGLT-2i) (n=40)as add-on to metformin. We measured at baseline, 4 and 12 months post-treatment: a) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25μm) using Sideview Darkfield imaging. Increased PBR indicates reduced glucocalyx thickness, b) pulse wave velocity (PWV-Complior), central systolic blood pressure (cSBP) and augmentation index (AI) of the aortic pulse wave.

Results
Twelve months post-treatment, all patients improved PBR, PWV and AI (p&lt;0.05). GLP-1RA, SGLT-2i and their combination showed a greater reduction of PBR, PWV and cSBP than insulin, despite a similar HbA1c reduction (p&lt;0.05). SGLT-2i or combined therapy with GLP-1RA and SGLT-2i showed a greater decrease of PWV (−10.1% and −13% vs. −3.6% and −8.6%) and cSBP (−3% and −5.5% vs. −0.8% and −1.5%)than insulin or GLP-1RA (p&lt;0.05 for all comparisons). GLP-1RA or GLP-1RA+SGLT-2i provided a greater decrease of AI (−42.7% and −48.6% vs. +6.2% vs. −3.8%) compared with insulin or SGLT-2i (Table). The dual therapy showed the greatest effect on measured markers in patients with LVEF &lt;55% (p&lt;0.05).

Conclusions
Twelve-month treatment with SGLT-2i and its combination with GLP-1RA, showed a greater improvement on arterial elastic properties than GLP1RA or insulin treatment in T2DM. The combined therapy as second line was superior to either insulin, or GLP-1RA and SGLT-2i separately.

Funding Acknowledgement
Type of funding source: None
Endovascular treatment of peripheral artery disease is associated with improved central hemodynamics and ventricular function
Authors: Messiha D , Halfmann L , Azizy O , Steinmetz M , Rassaf T , Rammos C 
Published: November 2020

Abstract

Background
Peripheral artery disease (PAD) is a major manifestation of atherosclerosis and a risk factor for morbidity and mortality. PAD itself is associated with increased arterial stiffness with impact on cardiac functions. Previous studies have demonstrated that augmentation index (AIx) and central blood pressure (CBP) correlate with increased cardiovascular mortality. This mechanism has been described as arterio-ventricular (AV) coupling with altered ventricular afterload and a depressed ventricular function, measured by global longitudinal strain (GLS). The impact of PAD-related endovascular treatment on arterial stiffness, central hemodynamics and potential impact on AV coupling has not been elucidated until now.

Purpose
Aim of the study was to investigate, if endovascular treatment of PAD improves cardiac function via enhanced central hemodynamics and AV coupling.

Methods
To this aim 77 patients with known symptomatic PAD who underwent interventions in the iliac and femoropopliteal arteries were included in a cross-sectional study. AIx, CBP and GLS were determined using dedicated waveform analysis and echocardiography before and after endovascular treatment.

Results
Mean age was 65.1±10.4 years with 66.2% male patients. Symptoms were classified by Fontaine classification (stage IIb 80.7%, stage III 5.8% and stage IV 13.5%). Iliac vessel intervention was performed in 16 and femoropopliteal intervention in 61 cases. A stentless approach was feasible in 55 patients with DCB treatment and atherectomy.
After endovascular treatment, peripheral perfusion was enhanced (ABI 0.45±0.6 vs 0.81±0.5, p&lt;0.0001). Moreover, central hemodynamics were improved (AIX 33.7±3% vs 27.9±2%, p=0.0008; AP 17.8±2 mmHg vs 14.0±2 mmHg, p=0.0004; central PP 52.4±6 mmHg vs 46.4±6 mmHg, p=0.0001). Impressively, left ventricular function was also significantly improved (GLS −15.7±2.3% vs −17.1±2.8%, p=0.005) with an improvement in AV coupling (PWV/GLS ratio −0.58m/sec% vs −0.56m/sec%, p&lt;0.01).

Conclusion
Our results demonstrate that endovascular treatment of the peripheral vessels is associated with an improvement of central hemodynamics and left ventricular function via enhanced AV coupling. These prognostic relevant markers of cardiovascular disease could point to an overall potential mortality benefit through PAD treatment. Further investigation of the underlying mechanisms of AV coupling in the setting of endovascular treatment of PAD with impact on cardiovascular mortality is needed in this high-risk population.

Funding Acknowledgement
Type of funding source: None
Clinical usefulness of Lipoprotein(a) for the prevalence and severity of peripheral artery disease among patients with acute coronary syndrome
Authors: Okubo R , Aikawa H , Matsumoto S , Noike R , Yabe T , Nakanishi R , Amano H , Toda M , Ikeda T 
Published: November 2020

Abstract

Background
Lipoprotein(a) [LP(a)] is known to be a robust lipid marker associated with cardiovascular events. Though coronary artery disease and peripheral artery disease (PAD) are often coexist, little is known about the relationship between LP(a) and PAD among patients with acute coronary syndrome (ACS).

Purpose
The purpose of this study is to examine if LP(a) is of predictive value for PAD among ACS patients in Japanese population.

Methods
Of consecutive 238 ACS patient who received successful primary PCI, a total of 175 patients were enrolled in the current study. We excluded the patients who received hemodialysis (n=10), required multidisciplinary treatment (n=36) and incomplete data (n=17). PAD was diagnosed as ankle brachial index &lt;0.9. Multiple lipid biomarkers [LP(a), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), malondialdehyde-modified LDL (MDA-LDL), docosahexaenoic acid and arachidonic acid] were compared between patients with PAD (n=21) and without PAD (n=154). Further, multivariable logistic regression models were used to assess if LP(a) was associated with PAD. In addition, serum LP(a) level were compared between 3 groups according to pattern of PAD [none (n=154), unilateral (n=10) and bilateral PAD (n=11), respectively].

Results
Compared to patients without PAD, those with PAD were older (74.4 vs. 65.4 years, p=0.003), and had a higher prevalence of chronic kidney disease (CKD) (61.9% vs. 20.1%, p&lt;0.001), diabetes mellitus (DM) (66.7% vs. 27.3%, p&lt;0.001). Serum LP(a) level was significantly higher in patients with PAD (36.4 vs. 18.5 mg/dl, p&lt;0.001), whereas LDL-C and MDA-LDL were significantly lower in PAD (92.0 vs. 109.5 mg/dl, p=0.015 and 98.6 vs. 119.5 mg/dl, p=0.046, respectively). After adjusting for LDL-C and MDA-LDL, LP(a) &gt;30 mg/dl was independently associated with a presence of PAD (OR 5.67, 95% CI 2.09–15.4, p=0.0006). When adjusting for CKD and DM in a different model, LP(a) &gt;30 mg/dl was similarly associated with PAD (OR 4.98, 95% CI 1.66–14.9, p=0.004). Serum LP(a) levels were significantly higher in bilateral PAD group compared to none PAD group (Figure).

Conclusion
LP(a) was a useful lipid biomarker for the prevalence and severity of PAD among patients with ACS in Japanese population.

Funding Acknowledgement
Type of funding source: None
Assessment of internal carotid artery stenosis and results of carotid stenting by angiography compared with intravascular ultrasound
Authors: Stechovsky C , Hajek P , Roland R , Horvath M , Veselka J 
Published: November 2020

Abstract

Background/Introduction
Intravascular imaging is commonly used in coronary interventions and improves outcomes. On the contrary, it is almost unrecognized for the guidance of carotid stenting (CAS).

Purpose
The aim of this study was to compare quantitative angiography (QA) and intravascular ultrasound (IVUS) in the assessment of the severity of carotid stenosis and residual stenosis in patients undergoing CAS and to provide reference values for IVUS measurements of the internal carotid artery (ICA) in the European population.

Methods
IVUS imaging was performed during 151 CAS procedures in 140 patients from April 2013 to December 2019. In total 162 self-expanding stents of different design were implanted (66% closed-cell, 22% open-cell, 8% hybrid, 4% double layer micromesh stents). IVUS was used to measure distal reference diameter and area of ICA, minimal luminal diameter (MLD) and minimal luminal area (MLA) before and after CAS. IVUS and QA were used to measure relative stenosis area (stenosis) at baseline and relative residual stenosis area (residual stenosis) after CAS. Relative stenosis area was calculated as [1 − (MLA / distal reference area)] x 100.

Results
Mean (±SD) distal reference diameter of ICA was 4.5±0.8 mm. MLD increased from 1.9±0.4 mm to 3.6±0.6 mm after CAS (p&lt;0.001). MLA increased from 3.9±1.7 mm2 to 12.0±3.4 mm2 after CAS (p&lt;0.001). Stenosis measured by QA and IVUS was 84±9% and 76±13% respectively (p=0.01). There was a moderate correlation (Pearson's correlation coefficient r=0.575; p=0.01) between QA and IVUS measurement of ICA stenosis severity. Residual stenosis measured by QA and IVUS was 12±10% and 40±16% (p&lt;0.001) respectively with only weak correlation (r=0.433; p&lt;0.001) between the two methods.

Conclusion
Angiography slightly overestimates stenosis of internal carotid artery and substantially underestimates residual stenosis after CAS compared to IVUS. Angiography alone is inaccurate in the assessment of ICA stenosis and results of carotid stenting.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): University Hospital Motol
Are there mortality differences between men and women in all types of intracranial hemorrhages: subarachnoid, intraparenchymal and subdural? An analysis of the Spanish population
Authors: Fernandez De Bobadilla Osorio J , Rey-Blas J.R , Gonzalez-Aguado N , Fuentes B , Masedo P , Iniesta A , Pena-Conde L , Rivero B , Severo A , Juarez V , Lopez De Sa E , Poveda D , Arbas E , Tebar D , Lopez-Sendon J.L 
Published: November 2020

Abstract

Objectives
There are 3 types of intracranial hemorrhage (ICH): 1) subarachnoid hemorrhage (SAH), CIE10:I60; 2) intraparenchymal hemorrhage (IPH), I61 and 3) subdural hemorrhage (SDH) I62. Epidemiological data on this field are scarce in Mediterranean countries. Our goal was to determine whether the relationship of ICH mortality with gender and age was different for the 3 types of HIC.

Methods
Data were retrospectively obtained from the Spanish National Institute of Statistics. Deaths/100.000 population of SAH, IPH and SDH were assessed for the entire Spanish population since 2008 to 2017 (n=46,527,039). Year 2017 was the last available for analysis. Incidence was analyzed for men and women and for age strata (&lt;1 years of age, 2–10, 11–20, 21–30, 31–40, 41–50, 51–60, 61–70, 71–80; &gt;80).

Results
In order to fit in the abstract space, only data of 2017 are presented, although years 2008 to 2017 were also analyzed and results were similar. Mortality/100,000 of IPH stayed very low under 40 years of age and then grew exponentially in both, men and women, and was significantly higher for men for all age strata. Mortality of SDH was much lower but behaved in a similar way: exponential growth since 40s and lower incidence in women. SAH behaved differently: it started to be significant since 20 years of age and there were no gender differences.

Conclusion
Mortality of intraparenchymal and subdural hemorrhage increases exponentially since 40 years of age and is lower in women. On the contrary, mortality of subarachnoid hemorrhage increases earlier and there are no gender differences.
Death/100.000 intracranial hemorrhage

Funding Acknowledgement
Type of funding source: None
Endovascular treatment in acute ischemic stroke: collaboration between neurologists and cardiologists in a single center
Authors: Petrov I , Klissurski M , Stankov Z , Tasheva I , Polomski P 
Published: November 2020

Abstract

Background
Several randomized trials have indicated a benefit from endovascular therapy in acute ischemic stroke (AIS) patients. In some centers, interventional cardiologists with previous large carotid stenting experience can play significant role for this treatment.

Objectives
We present retrospective analysis of prospectively collected data of endovascular treatment of stroke (EVTS) performed by interventional cardiologists in collaboration with neurologists in 46 patients in single center.

Methods
Between 2014 and 2017 46 consecutive AIS patients underwent EVT, men 69.7% (7 with posterior circulation stroke and 5 with wake-up stroke), with mean age 64.6±13 years and average National Institutes of Health Stroke Scale (NIHSS) score of 12.2±5 at presentation. During the same period of time 20 patients, 16 men, at mean age 69.4±12, and NIHSS score 11.8±7 received IVT. In the EVT group two methods were applied:
Method 1, Supraselective intra-arterial thrombolysis (IAT) alone or IAT plus balloon angioplasty (PBA);
Method 2, Aspiration with Penumbra aspiration system (PAS) or Combination of PAS plus low dose IAT.

Results
The mean symptoms onset-to-treatment (needle) time (ONT) in the EVT group was 221.7±121.5 minutes, and 185.5±34.9 in the IVT group (p=0.19T). Conscious sedation and local anesthesia was used in 84.7% of the patients (40), general anesthesia in 15.2%; preprocedural MRI was performed in 58.7% and CT in 71.7% of the patients. In the EVT group successful reperfusion (TICI 2b-3 flow) was achieved in 35 (76.1%) patients: in 73.9% with Method 1 and in 86.7% with Method 2 (p=0.44). Poor or no recanalization (TICI 0–1-2a) was observed in 26.1%. Twenty six of 46 patients (56.5%) treated with endovascular methods and respectively 9 (45%) with IVT demonstrated favorable clinical outcome of mRS score 0–2 at 90 days (p=0.91). The overall 3-month mortality was 15.2%, 13% after EVT and 20% after IVT (p=0.48).

Conclusions
Our initial experience with EVT of AIS performed by trained cardiologists with carotid experience is encouraging, with a relatively moderate to high rate of successful angiographic recanalization and good clinical results.

Funding Acknowledgement
Type of funding source: None
Efficacy of rivaroxaban compared to standard of care in preventing ischemic stroke in adults with coronary or peripheral vascular disease: an integrated analysis using patient-level data
Authors: Barnathan E.S , Deng H , Sun X , Dong X , La Police D , Suh E , Yuan Z , Berlin J.A 
Published: November 2020

Abstract

Background
Ischemic stroke is a leading cause of morbidity and mortality. Rivaroxaban has been evaluated in multiple studies of patients with coronary artery disease and/or peripheral artery disease (CAD/PAD) in which ischemic stroke was assessed.

Purpose
To determine the efficacy of rivaroxaban compared with standard of care (SOC) in reducing ischemic stroke in adults with CAD/PAD.

Methods
Randomized, active- or placebo-controlled Phase 2 or 3 studies evaluating rivaroxaban (2.5 mg twice daily) in adults with CAD/PAD in which ischemic stroke was collected as an efficacy endpoint were included using patient-level data. All stroke was also evaluated as a secondary outcome. ISTH major bleeding (MB) was assessed on treatment + 2 days. Hazard ratios (HR) and p-values for the treatment effect were estimated using Cox proportional hazards models and log-rank tests, respectively, with study as the stratification factor. Mixed effect Cox models (frailty models) were used with treatment as the fixed effect and study as the random effect. Cumulative risk of time-to-first event was assessed using the Kaplan-Meier method.

Results
Six studies were included: ATLAS-1, ATLAS-2, COMPASS, COMMANDER HF, GEMINI ACS1 and PIONEER AF-PCI (n=38,283). Compared with SOC, rivaroxaban significantly reduced the risk of ischemic stroke (HR, 0.63, 95% CI, 0.52–0.77, P&lt;0.001) and all stroke (HR, 0.71, 95% CI, 0.59–0.84, P&lt;0.001), without significant heterogeneity. The frailty model results were consistent. The risk of MB was significantly higher with rivaroxaban compared with SOC (HR, 1.58, 95% CI, 1.37–1.83, P&lt;0.001).

Conclusion
Rivaroxaban (2.5 mg twice daily) significantly reduced ischemic stroke and all stroke compared with SOC in patients with acute or chronic CAD/PAD while increasing MB.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Janssen Research and Development
Stroke prevention by Non-vitamin K Oral Anticoagulant (NOAC) agents in the absence of atrial fibrillation: meta-analysis of randomized control trials
Authors: Lander K , Thakeria P , Andrew H , Nayyar S 
Published: November 2020

Abstract

Background
Anticoagulation to prevent stroke is a mainstay of atrial fibrillation (AF) management. Patients with established cardiovascular disease (CVD) may have conditions that fulfil Virchow's triad for thrombogenesis even in sinus rhythm. Previous investigation into the benefit of warfarin compared to placebo or antiplatelet drug in sinus rhythm found a reduction in stroke rates, but with an increase in bleeding. The efficacy and safety of non-vitamin K oral anticoagulant (NOAC) agents has not been studied.

Purpose
To assess the safety and efficacy of NOAC agents in patients without AF.

Methods
An electronic database search for randomized controlled trials that evaluated a NOAC and control drug (placebo or antiplatelet) in non-AF patients with CVD was conducted up until 1 September 2019. The primary efficacy and safety outcomes were ischemic stroke and major bleeding, respectively. The net clinical benefit (NCB) was calculated as a weighted sum of rate differences of ischemic stroke and major bleeding. Groups were stratified according to intensity of anticoagulation (full vs. low dose NOAC).

Results
Twelve randomized controlled trials were identified with a total of 83,008 patients (50,617 on NOAC, 32391 on control drug; mean age 66±2.7 years). CVD included coronary artery disease (78.3%), hypertension (73.7%), diabetes mellitus (34.7%), peripheral arterial disease (30.3%), previous stroke (21.7%), renal disease (22.9%) and heart failure (18.4%). Over a mean follow-up of 17.3 months, 1347 (1.6%) ischemic strokes occurred. Use of NOAC was associated with 28% reduction in ischemic stroke (odds-ratio [OR] 0.72, 95% confidence-interval [CI] 0.60 to 0.87; 1.1 vs. 1.8 events per 100-person years), with numbers needed to treat of 145 patients to prevent one stroke. Major bleeding was increased nearly 2-fold (OR 1.83, 95% CI 1.46 to 2.29; 2.1 vs. 1.0 events per 100-person years). The NCB demonstrated overall harm with the use of NOAC agents in this patient population (NCB = −0.28, 95% CI: −0.79 to 0.23). Use of full dose NOAC was widely unsafe (NCB = −0.35, 95% CI: −1.25 to 0.54) and low dose NOAC approached null therapeutic safety advantage (NCB = −0.06, 95% CI: −0.47 to 0.35).

Conclusion
Patients with CVD are at increased of ischemic stroke in the absence of AF. The use of NOAC agents in this non-AF population reduces rate of ischemic stroke however overall risk of bleeding exceeds antithrombotic benefit. Low-dose NOACs demonstrate a neutral NCB suggesting a point of clinical equipoise and deserve further scrutiny.
Ischemic stroke vs major bleeding

Funding Acknowledgement
Type of funding source: None