bluuebunny/crossref_metadata_2025_split huggingface dataset:
252Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome and multivessel coronary artery disease: a post-hoc analysis of the TROPICAL-ACS trial
Authors: Rizas K D , Gross L , Trenk D , Komocsi A , Baylacher M , Orban M , Loew A , Massberg S , Aradi D , Sibbing D 
Published: October 2019

Abstract

Background
The TROPICAL-ACS trial showed that platelet function testing (PFT) guided de-escalation of P2Y12-inhibitor is a safe alternative treatment strategy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). No specific data are available on the efficacy of this strategy in patients with multivessel coronary artery disease (CAD).

Purpose
To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with multivessel CAD.

Methods
Two-thousand six-hundred-two biomarker-positive ACS patients were 1:1 randomized to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint (net clinical benefit) was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used log-rank statistics and Cox regression analysis with interaction testing to assess the effect of multivessel CAD on the primary and ischemic endpoints.

Results
Patients with multivessel (n=709) versus single-vessel CAD (n=1,901) exhibited a higher risk for the primary endpoint (10.2% vs. 7.6%; HR 1.36; 95% CI 1.02–1.81; p=0.034). Guided de-escalation was non-inferior to conventional treatment for the primary endpoint in both patients with single-vessel CAD (6.7% vs. 8.5%; pnon-inferiority = 0.001; Figure 1A) and multivessel CAD (9,5% vs. 10.9%; pnon-inferiority=0.041; Figure 1B). Moreover, there was no significant interaction in the prognostic value of guided de-escalation between single-vessel and multivessel CAD for both the primary (HR 0.78 [0.56–1.08]; p=0.137 in patients with single-vessel CAD vs. 0.86 [0.54–1.37; p=0.524 in patients with multivessel CAD; pinteraction=0.732) and combined ischemic endpoints (HR 0.80 [0.44–1.45]; p=0.456 in patients with single-vessel CAD vs. 0.71 [0.35–1. 46]; p=0.356 in patients with multivessel CAD; pinteraction=0.823).
Kaplan-Meier curves

Conclusion
A guided de-escalation of P2Y12-inhibitor appears to be safe and effective in ACS patients with both single-vessel and multivessel CAD.

Acknowledgement/Funding
Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.
284Outcomes after left atrial appendage occlusion with AMPLATZER Amulet and WATCHMAN device: Results from the ORIGINAL registry (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure)
Authors: Kretzler L , Wunderlich C , Christoph M , Langbein A , Spitzer S G , Gerk U , Schellong S , Ketteler T , Neuser H , Schwefer M , Strasser R H , Mues C , Ibrahim K , Schoen S P 
Published: October 2019

Abstract

Aims
Left atrial appendage occlusion (LAAO) is a therapeutic option for patients with non-valvular atrial fibrillation (NVAF) and high risk of bleeding. This study reports outcomes of patients enrolled in the prospective multicentre, investigator initiated real life registry in the Free State of Saxony (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure).

Methods and results
Data of all consecutive 521 patients (64.7% adult males, 35.3% adult females, mean age: 75.1 (SD 7.9) years with non-valvular atrial fibrillation undergoing interventional left atrial appendage occlusion procedure in the ORIGINAL prospective registry were analysed. The CHA2DS2-VASc and HAS-BLED scores were 4.3 (SD 1.5) and 3.7 (SD 1.1), respectively. 78.9% of the patients had a history of bleeding. 89.3% of the patients were considered as non-eligible for long term oral anticoagulation. A left atrial appendage occlusion device was successfully implanted in 97.5% of cases. A mean follow-up of 463 days could be reached in 386 patients. Among these, the distribution of the follow-up length reached was as follows: 1 year 205, 2 years 118, 3 years 65 and 4 years 17 patients. In the follow-up the annual frequency of stroke was very low (0.4%), which resulted in the 4.98% absolute risk reduction in the amount of thromboembolic strokes, which would have been expected according to the calculated CHA2DS2-VASc score in the hypothetic group not receiving any anticoagulant therapy. The occurrence of major and minor bleeding in the follow-up was 1.55% and 3.37% respectively.

Conclusions
In this prospective multicentre study we included the patients who are at high risk of stroke and bleeding. The annual ischemic stroke rate was 0.4%, the LAA could be sealed in 97.5%. Six months after the LAA closure only 3.63% of all patients were further on treated using oral anticoagulation. Considering the stroke reduction rates, the implantation of an LAAO device proves to be effective and safe in the clinical routine in the studied population.

Acknowledgement/Funding
None
287Diabetes mellitus is a risk factor for ischemic stroke in patients with and without coronary artery disease after coronary angiography
Authors: Olesen K K W , Madsen M , Gyldenkerne C , Thrane P G , Wurtz M , Thim T , Jensen L O , Eikelboom J W , Botker H E , Sorensen H T , Maeng M 
Published: October 2019

Abstract

Background
Diabetes (DM) and non-DM patients without coronary artery disease (CAD) by coronary angiography (CAG) have the same low risk of myocardial infarction.

Purpose
To study whether DM patients without CAD have the same risk of ischemic stroke as patients with neither DM nor CAD.

Methods
We conducted a cohort study of patients, who underwent CAG between 2004 and 2012 in the Western Denmark Heart Registry. Patients previously diagnosed with ischemic stroke or atrial fibrillation (AF) and those treated with an oral anticoagulant were excluded. Patients were stratified according to presence of DM and CAD. Follow-up started 30 days after CAG. We computed event rates and adjusted incidence rate ratios (IRRs) using patients with neither DM nor CAD as reference.

Results
A total of 68,829 patients were included. Median follow-up was 4.0 years. Patients with both DM and CAD were at the highest risk of ischemic stroke (1.25 events per 100 person-years; adjusted IRR 2.10, 95% CI 1.77–2.48) (Figure 1). Patients with CAD alone (0.70 events per 100 person-years; adjusted IRR 1.29, 95% CI 1.12–1.48) or DM alone (0.84 events per 100 person-years; adjusted IRR 1.79, 95% CI 1.41–2.26) were at intermediate risk while patients with neither DM nor CAD (0.46 events per 100 person-years) were at lowest risk. Among DM patients, extent of CAD was further predictive of risk (ptrend<0.001).
Figure 1

Conclusions
Not only CAD but also DM independently predict the risk of ischemic stroke after CAG. Their combination further increases the risk of ischemic stroke depending on the extent of CAD.
428In-hospital coronary angiography is associated with increased evidence based medications and better survival in patients hospitalized with acute heart failure - results from REALITY-AHF
Authors: Akiyama E , Konishi M , Okumura T , Kida K , Oishi S , Suzuki S , Yamamoto M , Kitai T , Matsue Y 
Published: October 2019

Abstract

Background
Coronary artery disease is a major cause of heart failure (HF). Urgent coronary angiography (CAG) is recommended for patients with acute HF (AHF) complicated with acute coronary syndrome (ACS); however, clinical usefulness of in-hospital CAG in AHF patients without ACS remains unknown.

Purpose
To investigate the association between in-hospital CAG and all-cause mortality at 1-year after hospital discharge and effects of medications at discharge on this association.

Methods
From the REALITY-AHF study, 1344 patients hospitalized with AHF were enrolled in this study and followed up for 1-year after hospital discharge.

Results
In-hospital CAG was undergone in 511 patients (38%). CAG group had a significantly lower 1-year mortality compared with non-CAG group (unadjusted hazard ratio [HR]; 0.30, 95%-confidence interval [CI] 0.21–0.43, P<0.001, after adjustment for MAGGIC score; HR 0.45, 95%-CI 0.29–0.70, P<0.001, in propensity-score matched 296 pairs; HR 0.60, 95%-CI 0.37–0.98, P=0.04). At discharge, aspirin, statins and beta blockers were prescribed more in CAG group compared with non-CAG group (aspirin 46% versus 30%, P<0.001, statins 51% versus 35%, P<0.001, and beta blockers 76% versus 65%, P=0.007). The prescription of aspirin or statins at discharge was associated with a better 1-year survival in patients with multivessel disease (P<0.001), but not in patients without significant stenosis or single vessel disease (P=0.95) (Figure).
CAG results, medications and mortality

Conclusions
In patients hospitalized with AHF, in-hospital CAG was associated with increased evidence based medications at discharge and a better long-term survival. Aspirin and statins at discharge might improve outcomes in AHF patients with multivessel disease.

Acknowledgement/Funding
This study was funded by The Cardiovascular Research Fund, Tokyo, Japan.
455Prediction of major bleeding in patients receiving DOACs for venous thromboembolism: a prospective cohort study
Authors: Vedovati M C , Mancuso A , Pierpaoli L , Paliani U , Conti S , Ascani A , Galeotti G , Di Filippo F , Caponi C , Agnelli G , Becattini C 
Published: October 2019

Abstract

Background
The accuracy of currently available bleeding scores in patients on treatment with direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) is undefined.

Purpose
In a prospective cohort of patients with VTE treated with DOACs, we evaluated the accuracy of the ATRIA, HAS-BLED, Kuijer, ORBIT, RIETE and VTE-BLEED risk scores in predicting major bleeding (according to ISTH definition).

Methods
The accuracy of different scores to correctly classify subjects into a defined risk category was assessed by the c-statistic.

Results
Overall, 1141 patients were evaluated and 1034 included in the study. The index event was pulmonary embolism in 509 patients (49.2%) and proximal deep vein thrombosis in the remaining patients (50.8%). During the 12-month study period, 26 major bleedings occurred in 25 patients (2.8% patient-year): 14 major bleedings occurred in the first 6 months of treatment and 12 from 6 to 12 months in the 654 patients remained on treatment.
In the 12-month study period, the VTE-BLEED score showed the best predictive value for bleeding complications (c-statistics 0.674, 95% CI 0.593–0.755). The lowest incidence of major bleeding (0.3%) was observed in the low risk category of VTE-BLEED which includes 38% of patients. The highest incidence of major bleeding (7.1%) was observed in the high-risk category of ORBIT which includes 10.9% of patients.

Conclusions
The VTE-BLEED score had the best accuracy in predicting major bleeding during treatment with DOACs for VTE. Whether the VTE-BLEED score can be used for decision making on anticoagulation should be tested in a management study.
456Risk of arterial calcification by conventional vitamin K antagonist treatment
Authors: Hasific S , Oevrehus K A , Gerke O , Hallas J , Busk M , Lambrechtsen J , Urbonaviciene G , Roennow Sand N P , Nielsen J S , Diederichsen L , Pedersen K B , Mickley H , Rasmussen L M , Lindholt J S , Diederichsen A 
Published: October 2019

Abstract

Background
Vitamin K antagonists (VKA) are the most frequently prescribed oral anticoagulants worldwide although new oral anticoagulants (NOAC) have become an important alternative. VKA inhibits Vitamin K1 necessary to produce coagulation factors but also Vitamin K2, which is essential in the activation of matrix-Gla protein, thought to be a strong local inhibitor of arterial calcifications.

Purpose
The aim was to investigate, whether VKA treatment is associated with coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD).

Methods
We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n=9,672) or research studies (n=14,166) in the period 2007–2017. Data on use of VKA and NOAC was obtained from the Danish National Health Service Prescription Database. The association between VKA treatment duration and categorized CAC score was investigated by ordered logistic regression while adjusting for covariates. The independent variables included in the model were: age, gender, smoking, body mass index (BMI), diabetes mellitus, hypertension, hypercholesterolemia and/or statin treatment, family history of CVD, estimated glomerular filtration rate, VKA treatment duration and NOAC treatment duration. The categorisation of CAC was: 0, 1–99, 100–399 and ≥400 AU, corresponding to no, mild, moderate and severe atherosclerotic plaque burden, respectively.

Results
The final study population consisted of 17,254 participants (median 67 years old, 75% males) with no prior CVD, of which 1,748 (10%) and 1,144 (7%) had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories (Figure). For each cumulative year of VKA treatment, the odds of being in a higher CAC category, i.e. having more severe atherosclerosis, increased (odds ratio (OR)=1.032, 95% CI 1.009–1.057). All traditional cardiovascular risk factors were also associated with CAC. In contrast, NOAC treatment duration was not associated with CAC category (OR=1.004, 95% CI 0.937–1.075). In a sensitivity analysis of patients without statin treatment (n=12,143), the association between VKA treatment and CAC category remained unchanged. There was no significant interaction between VKA treatment duration and age on CAC category.

Conclusion
Adjusted for cardiovascular risk factors, VKA treatment – in contrast to NOAC - is associated with more severe CAC. Additional studies are required to clarify the clinical importance of this association in terms of hard cardiovascular endpoints.

Acknowledgement/Funding
Novo Nordisk Foundation and Independent Research Fund Denmark
458Real world persistence with direct oral anticoagulants in anticoagulation naive patients with atrial fibrillation
Authors: Denas G , Costa G , Ferroni E , Gennaro N , Fedeli U , Corti M C , Zoppellaro G , Padayattil Jose S , Pengo V 
Published: October 2019

Abstract

Introduction
Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications.

Purpose
To assess persistence levels of DOACs and look for possible predictors of treatment discontinuity in NVAF patients.

Methods
We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression.

Results
Overall, 17920 patients initiated anticoagulation with DOACs in the study period. Most patients were older than 74 years old, while gender was almost equally represented. Comorbidities included hypertension (72%), diabetes mellitus (17%), congestive heart failure (9%), previous stroke/TIA (20%), and prior myocardial infarction (2%). After one year, the persistence to anticoagulation treatment was 82.7%, while the persistence to DOAC treatment was 72.9% with about 10% of the discontinuations being due to switch to VKAs. On multivariate analysis, factors negatively affecting persistence were female gender, younger age (<65 years), renal disease and history of bleeding. Conversely, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction.
Persistence to DOAC therapy

Conclusion
This real-world data show that within 12 months, one out of four anticoagulation-naïve patients stop DOACs, while one out of five patients stop anticoagulation. Efforts should be made to correct modifiable predictors and intensify patient education.
460Edoxaban versus warfarin in atrial fibrillation patients with low, mid and high body weight: analysis of outcomes in the engage AF TIMI 48 trial
Authors: Boriani G , Ruff C T , Kuder J F , Shi M , Lanz H , Antman E M , Braunwald E , Giugliano R P 
Published: October 2019

Abstract

Background
The impact on outcomes of oral anticoagulants in pts at extremes of body weight have not been well-characterized.

Aim
To analyse the outcomes of pts with atrial fibrillation (AF) enrolled in ENGAGE AF-TMI 48 randomized to warfarin (W) targeting INR 2.0–3.0, higher (HDE) or lower dose regimens of edoxaban (LDE), focusing on subgroups of patients at the extremes of weight.

Methods and results
Among 21105 pts enrolled in the trial we identified 3 subgroups: 1082 with low body weight (LBW) (<5th percentile, <55kg), 2153 with mid body weight (MBW) (45–55th percentile, 80–84 kg), and 1093 patients with high body weight (HBE) (>95th percentile, >120 kg). Baseline characteristics differed markedly (LWB pts were older and more likely Asian, women, with prior TIA/stroke, renal dysfunction) resulting in a trend towards higher rates of stroke/systemic embolism (SSE: 6.5% vs 4.7% in MBW vs 1.6% in HBW) and major bleeding (MB: 9.3% vs 7.7% in MBW vs 6.5% in HBW) in the warfarin arm. The risks of SSE (Pint = 0.52) were similar between W and HDE regardless of body weight, while the relative reduction in MB was greatest in LBW patients (HR reduction45%, 23%, 1% across weight groups; Pint = 0.35) (Figure). Net clinical outcomes (SEE/major bleeding/death) tended to be most favourable for LBW pts (HR 0.67 [0.50–0.90]; Pint 0.084) (Figure).
Main outcomes during follow up

Conclusions
In ENGAGE AF-TIMI 48 the profile of AF pts with LBW markedly differed suggesting a more fragile clinical status. Use of dose-adjusted edoxaban, as compared to W, was associated with similar efficacy regardless of weight, while bleeding and net outcomes were most favourable in LBW pts.
464Optimal timing of invasive coronary angiography following NSTEMI
Authors: Mahendiran T , Nanchen D , Meier D , Gencer B , Klingenberg R , Raber L , Carballo D , Matter C , Luscher T , Windecker S , Mach F , Rodondi N , Muller O , Fournier S 
Published: October 2019

Abstract

Introduction
Current guidelines recommend angiography within 24 hours of hospitalisation for patients with non-ST elevation myocardial infarction (NSTEMI). The recent VERDICT study found that angiography within 12 hours of hospitalisation was associated with improved cardiovascular outcomes among high-risk patients. We aimed to obtain a real-world perspective of the impact of angiography timing on one-year outcomes of patients admitted with NSTEMI.

Methods
Data was obtained from the SPUM-ACS registry, a cohort of consecutive patients hospitalised with acute coronary syndromes in four university hospitals in Switzerland between 2009 and 2017. Patients without a door-to-catheter (DTC) time and those with life-threatening features were excluded. Cox proportional hazards models evaluated the impact of DTC time on the primary endpoint, defined as one-year major adverse cardiovascular events (MACE: cardiovascular mortality, myocardial infarction, stroke), and on one-year all-cause mortality.

Results
Of 2,672 NSTEMI patients, 1,832 met the inclusion criteria. Among them, 1,464 patients underwent angiography within 12 hours of admission (12h group) while 368 patients underwent angiography between 12 and 24 hours (12–24h group). After 2:1 propensity score matching, 736 patients from the 12h group and 368 patients from the 12–24h group were deemed equivalent in terms of main baseline clinical characteristics. Multiple logistic regression identified admission out-of-hours (night or weekend) as the most significant factor associated with delayed angiography. Cox models found no significant association between early angiography and one-year MACE (12h group: n=57 (7.7%) vs. 12–24h group: n=27 (7.3%), HR: 1.050, 95% CI 0.637- 1.733, p=0.847), or one-year all-cause mortality (12h group: n=25 (3.4%) vs. 12–24h group: n=17 (4.6%), HR: 1.514, 95% CI 0.774- 2.962, p=0.225) (Figure 1A). After stratification based on GRACE score (>140 vs. ≤140), there was no significant difference in one-year MACE or one-year all-cause mortality in the 12h group compared with the 12–24h group (p for interaction=0.601 and 0.463, respectively) (Figure 1A + 1B).
Figure 1

Conclusion
In an unselected real-world cohort of NSTEMI patients, angiography within 12 hours of hospitalisation was not associated with improved one-year outcomes when compared with angiography between 12 and 24 hours, even among patients with an elevated GRACE score.