bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4725Prognostic relevance of the COAPT inclusion criteria in real-world patients with secondary mitral regurgitation undergoing mitraclip implantation
Authors: Iliadis C , Metze C , Koerber M I , Baldus S , Pfister R 
Published: October 2019

Abstract

Background
The recently published Cardiovascular Outcomes Assessment of the mitraclip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) randomized trial has shown a huge benefit in the survival of patients with systolic heart failure and functional mitral regurgitation treated with MitraClip. However, patients in COAPT were highly selected and the clinical course in real-world patients with and without fulfilment of the trial inclusion criteria is unclear.

Methods
Our study examined the clinical outcome in consecutive patients from our Heart Centre with reduced left-ventricular ejection fraction (EF<50%) undergoing mitraclip for mitral regurgitation of dominant functional etiology by the presence of the inclusion criteria of the COAPT trial (left ventricular ejection fraction >20%, left ventricular end-systolic dimension <70 mm, non-commissural primary jet, estimated pulmonary artery systolic pressure <70 mmHg, mitral valve orifice area >4 cm2, no prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve or any prior transcatheter mitral valve procedure). The composite endpoint of all-cause mortality or heart failure hospitalization and the endpoint of heart failure hospitalization were analysed.

Results
Among 123 patients who underwent mitraclip implantation 60.2% fulfilled the inclusion criteria of COAPT. Overall, 54 patients (46.6%) died or were hospitalized for heart failure during a median follow-up time of 19 months. The composite endpoint was significantly less frequent (p=0.01) in patients fulfilling the COAPT selection criteria than in those not fulfilling the criteria, with an estimated 1-year event rate of 24.6% vs 49.1%. Patients with COAPT inclusion criteria had a 49% lower hazard of the composite endpoint (95% CI 12–70%, p=0.015). Heart failure hospitalization was significantly less frequent (p=0.039) in patients fulfilling COAPT selection criteria than in those who did not, with an estimated 1-year event rate of 19% vs. 36.8%. Patients with COAPT inclusion criteria had a 50% lower hazard for heart failure hospitalization (95% CI 1–75%, p=0.046). Of note, the 1-year all-cause mortality in our patients fulfilling COAPT inclusion criteria was lower compared to the renowned COAPT trial (10% vs. 19%).

Conclusion
In this single center study the outcome of patients with functional mitral regurgitation undergoing mitraclip therapy was significantly worse in patients not fulfilling COAPT inclusion criteria, indicating that these criteria might help identify futility. The remarkable difference in outcome between real-world patients and COAPT trial patients warrants further study to elucidate underlying causes, which might affect the transferability of the COAPT results.
P4731Procedure-related acute thrombosis after surgical left atrial appendage occlusion for atrial fibrillation
Authors: Inoue T , Shimizu T , Yoshimoto A , Suematsu Y 
Published: October 2019

Abstract

Background/Introduction
Left atrial appendage (LAA) occlusion is an effective strategy for thromboembolism prevention in patients with atrial fibrillation (AF), and the novel methods of occlusion is various. The acute thrombosis after percutaneous LAA occlusion devices has been recently reported, but thrombus formation after surgical LAA occlusion is still unclear.

Purpose
This study aimed to analyse the incidence and prognosis of thrombus formation on closure stump line in patients with AF who underwent surgical LAA occlusion.

Methods
This study retrospectively analised the data from patients treated with two methods of surgical LAA closure, resection or clipping, from January 2014 to November 2018.

Results
A total of 187 consecutive patients with AF underwent surgical LAA closure (31 clipping and 156 stapler resection). 170 patients (91%) underwent cardiac CT for LAA imaging on postoperative day 2. The incidence of acute procedure-related thrombus formation in full cohort was 19% (35 cases). The incidence of acute thrombus in patients with clipping and resection was 19% and 16%, respectively (Fisher's exact test, p=0.8). All of 35 patients who had thrombus on LAA closure stump line underwent cardiac CT again 3 months after the primary CT. In all patients with secondary cardiac CT, thrombus on LAA closure stump line disappeared. No symptomatic thromboembolism occurred during the follow-up from operation to secondary CT scan.

Conclusion(s)
Thrombus formation on stump after surgical LAA closure may often occur on acute phase. The optimal LAA imaging and anti-coagulation therapy after surgical LAA occlusion will prevent patients with acute thrombus from thromboembolism.
P4733Risk of myocardial infarction with coronary artery bypass grafting versus percutaneous coronary intervention: a systematic review and meta-analysis of fifteen randomised trials
Authors: Lee P H , Park H B , Lee J S , Lee S W , Lee C W 
Published: October 2019

Abstract

Background
It remains controversial whether coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is more effective in the prevention of myocardial infarction (MI). MI has been evaluated only as a secondary endpoint without a focused systematic review in multiple meta-analyses.

Purpose
To compare the risk of MI at the latest follow-up available between CABG versus PCI with stents in patients with multivessel or left main coronary artery disease in a pairwise meta-analysis of randomised controlled trials (RCT).

Methods
We searched EMBASE, Cochrane, and Pubmed databases for articles comparing CABG versus PCI for the treatment of multivessel or left main disease. We utilised random-effects model to calculate pooled risk ratio (RR) and 95% confidence interval (CI). Fifteen trials with a total of 13,592 patients treated with either CABG (n=6,596) or PCI (n=6,996) were eligible and included. A multivariable random-effects meta-regression model, including variables such as age, sex, diabetes mellitus, publication year, follow-up duration, type of stent used, and type of coronary artery disease, was used to explore the source of potential heterogeneity of the primary result.

Results
After a weighted follow-up of 4.3 years, patients treated with CABG had a significantly lower risk of MI than patients treated with PCI (RR 0.75, 95% CI 0.58–0.96, P=0.024, I2=66%). The lower risk of MI with CABG as compared to PCI was more evident during a longer duration of follow-up (≥3 years, RR 0.69, 95% CI 0.52–0.91, P=0.008; ≥5 years, RR 0.64, 95% CI 0.48–0.86, P=0.003) and in diabetic population (RR 0.55, 95% CI 0.44–0.70, P<0.001). There was a statistically meaningful trend toward fewer MIs with CABG with a similar magnitude of risk reduction across patients with left main disease (RR 0.74, 95% CI 0.47–1.15) and multivessel disease (RR 0.72, 95% CI 0.53–0.99). Moderate inter-study heterogeneity could not be explained by the clinical and trial-based variables tested in meta-regression, and is likely because of differences in definitions of MI, risk profile of enrolled patients, and procedural specifics.
Forest plots

Conclusions
In patients undergoing revascularization for multivessel or left main disease, the risk of MI was lower with CABG compared to PCI. The quality assurance for MI definition and treatment-specific procedures should be emphasized for future RCTs.
P4738New combined risk score to predict atrial fibrillation after cardiac surgery
Authors: Burgos L M , Gil Ramirez A , Espinoza J C , Seoane L , Furmento J F , Miranda P R , Villalba L , Cracco M A , Polero L D , Baro Vila R , Berton F , Navia D , Benzadon M N 
Published: October 2019

Abstract

Introduction
Atrial fibrillation after cardiac surgery (AFCS) is associated with an increase in adverse events. The scores POAF, CHA2DS2-VASc and HATCH demonstrated a validated predictive to predict AF after CS (AFCS).

Purpose
To develop and validate a new risk score from the combination of the variables with highest predictive value of POAF, CHA2DS2-VASc and HATCH risk scores to predict AFCS.

Methodology
We conducted a single-center cohort study, performing a retrospective analysis of prospectively collected data. The study included consecutive patients undergoing CS between 2010–2016. The primary outcome was the development of new-onset AFCS during hospitalization. The variables of each score were evaluated in a multivariate regression model to determine the predictive impact. Discrimination was evaluated with area under the ROC curve (AUC-ROC) and calibration using the Hosmer-Lemeshow (HL) test. The Youden index was used to establish the best cut-off point for the score. The statistical difference between the ROC curves was evaluated with the method of DeLong et al.

Results
3113 patients were included. Coronary artery bypass graft surgery 45%, valve replacement 24%, combined procedure (revascularization-valve surgery) 15%, and other procedures 16%. 21% (n=654) presented AFCS. Variables finally included in the new score were: age (≥75: 2, 65–74: 1), heart failure (2), female sex (1), hypertension (1), diabetes (1), previous stroke (1). The new score presented an AUC of 0.78 (95% CI 0.78–0.80), the rest of the scores presented lower discrimination ability (P<0.001): CHAD2DS2-VASc AUC 0.76, POAF 0.71 and HATCH 0.70. The HL test showed a p>0.05. For the new score, the best cut-off point was 2, with a sensitivity of 82% and specificity of 65.9%, presenting high negative predictive value: 92.9%.
Variables OR (CI 95%) P Age (years)   65–74 3.14 (2.29–4.31) <0.001   ≥75 8.68 (6.32–11.93) <0.001 Female sex 3.36 (2.68–4.22) <0.001 Heart failure 2.45 (1.82–3.31) <0.001 Stroke/TIA 2.33 (1.45–3.76) <0.001 Hypertension 1.68 (1.28–2.2) <0.001 Diabetes 1.72 (1.31–2.25) <0.001

Conclusion
From the combination of variables with higher predictive value included in the POAF, CHA2DS2-VASc, and HATCH scores, a new risk system was created to predict AFCS, presenting a greater predictive ability than the original ones. Being necessary future prospective validations.
P4743Inappropriate dosing of non-vitamin K oral anticoagulants (NOACs) in atrial fibrillation patients in Europe
Authors: Palau I , Heinz S , Cheng B Y , Brown S 
Published: October 2019

Abstract

Background
Prescription of Non-vitamin K oral anticoagulants (NOACs) has increased since the first therapies were launched in Europe in 2011, and they are becoming the standard of care in prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). There are concerns about inappropriate NOAC dosing in clinical practice.

Purpose
This paper examines the extent of inappropriate dose prescription among NOAC patients in Germany, Italy, Spain and United Kingdom. Inappropriate dosing refers to patients who do not meet the criteria for dose reduction (under-dose) or patients who should be on the reduced dose as they meet the criteria for dose reduction (overdose).

Methods
Ipsos' Stroke Prevention in Atrial Fibrillation Therapy Monitor was fielded for 6 weeks between January 2017 to February 2017 and 6 weeks between January 2018 to March 2018, with 450 treating doctors in 2017 and 509 in 2018 providing data from 5,692 (2017: n=2,497, 2018: n=3,195) patients with non-valvular atrial fibrillation in Europe. We analysed the results for the 3,477 patients with a NOAC prescription that had sufficient data to decide on the appropriate dose.

Results
Overall, 23.4% of patients (n=813) were receiving an inappropriate dose of dabigatran, rivaroxaban, apixaban or edoxaban. Receiving an under-dose was more common than an overdose (19.2% vs 4.2%).
Ipsos data indicate 32.8% of NOAC patients in EU4 (n=1,139) were prescribed a reduced dose, and Italy had a higher proportion of patients who received a reduced dosed; Italy: 41.0% (n=345), Germany: 30.2% (n=402), Spain: 30.6% (n=216) and UK: 29.4% (n=176). Among these patients, a considerable proportion did not meet the criteria for dose reduction in EU4 (58.6%). This suggests that reduced dose is frequently prescribed to patients when not indicated.

Conclusion
Overall, the majority of patients were prescribed a correct dose according to the product label. However, we see evidence that nearly half of patients receiving a reduced dose were not indicated for a dose reduction. Further research is needed to identify reasons prompting the over-use of reduced dose.
P4745Concomitant oral anticoagulant and antidepressant therapy in patients with atrial fibrillation and risk of stroke and bleeding: a population based cohort study
Authors: Komen J J , Hjemdahl P , Mantel - Teeuwisse A K , Klungel O H , Wettermark B , Forslund T 
Published: October 2019

Abstract

Background
Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds.

Objective
To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk.

Methods
All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings.

Results
Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02).
Incidence rates of strokes and bleeds

Conclusion
Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population.

Acknowledgement/Funding
Swedish Heart Lung Foundation
P4747Impact of different estimates of renal function on cardiovascular mortality and major bleeding in patients with atrial fibrillation on oral anticoagulation
Authors: Hijazi Z , Granger C B , Hohnloser S H , Westerbergh J , Lindback J , Alexander J H , Keltai M , Parkhomenko A , Lopez-Sendon J L , Lopes R D , Siegbahn A , Wallentin L 
Published: October 2019

Abstract

Background
Renal dysfunction is associated with increased risk of cardiovascular events in atrial fibrillation (AF). Estimated glomerular filtration rate (eGFR) can be calculated by different equations based on creatinine or cystatin C. We compared different methods of assessing eGFR and their association with cardiovascular (CV) death and major bleeding in 14,980 AF patients in the ARISTOTLE trial.

Methods
eGFR was calculated using equations based on creatinine (Cockcroft-Gault, MDRD, and CKD-EPI) and/or cystatin C (CKD-EPIcys and CKD-EPIcys+crea). In total five eGFR equations as well as a model based on the variables within the equations were assessed. Associations were evaluated by Spearman correlation, and discriminatory ability for CV-death and major bleeding by Harrell's c-index.

Results
Median age was 70.0 years, and 35.6% were women. Median eGFR (mL/min) were: Cockcroft-Gault 74.1, MDRD 66.5, CKD-EPI 68.5, CKD-EPIcys 74.2, and CKD-EPIcys+crea 72.6. Correlation ranged from 0.49 (Cockroft-Gault and CKD-EPIcys) to 0.99 (MDRD and CKD-EPI). Among the eGFR equations, those based on cystatin C yielded the highest c-indices for CV-death and major bleeding, 0.628 (CKD-EPIcys) and 0.612 (CKD-EPIcys+crea), respectively. A model based on the variables within the eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, 0.673 and 0.656, respectively.
Figure 1

Conclusions
In patients with AF on anticoagulation, correlation between eGFR methods varied greatly. Cystatin C-based eGFR seem to provide the most robust balance in reflecting the risk of death and bleeding. However, a model based on the individual variables within the eGFR equations provided the highest discriminatory value.

Acknowledgement/Funding
The ARISTOTLE trial was funded by Bristol-Myers Squibb, Co Princeton, NJ and Pfizer Inc., New York, NY.
P4750Uninterrupted and minimally-interrupted direct oral anticoagulant therapy in patients undergoing catheter ablation for atrial fibrillation. An updated meta-analysis
Authors: Ottoffy M , Hegyi P , Habon T 
Published: October 2019

Abstract

Background
Adequate anticoagulation in catheter ablation of atrial fibrillation (AF) is crucial in preventing both thromboembolic events and life-threatening bleeding. As clinicians gain more experience and reassurance with data from clinical trials, the usage of Direct Oral Anticoagulants (DOAC) in patients undergoing catheter ablation of AF has rapidly increased over the last years. The purpose of this updated meta-analysis was to assess the latest evidence and compare the safety and efficacy of uninterrupted and minimally interrupted periprocedural DOAC anticoagulation protocols with uninterrupted Vitamin K Antagonists (VKA) in this setting.

Methods
Randomized or prospective controlled observational studies comparing DOACs to VKAs were identified with multiple databases (Embase, PubMed, Cochrane, and Scopus). Uninterrupted and minimally interrupted DOAC (single dose of dabigatran or apixaban withheld) were distinguished, VKA therapy was always uninterrupted. The primary outcomes were stroke or transient ischemic attack (TIA), major bleeding, and net clinical benefit.

Results
32 studies were included in the final analysis, encompassing a total of 19.437 patients. The incidence of thromboembolic events was rare (less than 0.2%), with no significant difference between groups. Occurrence of major bleeding and net clinical benefit were significantly improved in patients assigned to uninterrupted DOAC treatment compared to VKAs (1.5% vs 2.2%, POR: 0.74, CI: 0.56–0.98, I2=0,0% and 1.7% vs 2.4%, POR: 0.76; CI: 0.59–0.99, I2=0,0%, respectively).
Net clinical benefit

Conclusion
This updated meta-analysis, based on a large database, showed that DOAC therapy is equally effective as VKA in preventing stroke and TIA. Minimally-interrupted DOAC therapy is a non-inferior peri-procedural anticoagulation strategy, however, uninterrupted DOAC therapy showed superiority when compared to VKA regarding major, life-threatening bleeding. Our findings showed that uninterrupted periprocedural DOAC therapy is a safe and preferable alternative to VKAs in patients undergoing catheter ablation for atrial fibrillation.

Acknowledgement/Funding
This study was supported by an Economic Development and Innovation Operative Programme Grant (GINOP 2.3.2-15-2016-00048).
P4754Time to discontinuation of non-vitamin k antagonist oral anticoagulants in patients with non-valvular atrial fibrillation
Authors: Garcia Rodriguez L A , Vora P , Brobert G , Lenz Y , Ruigomez A 
Published: October 2019

Abstract

Background
Despite widespread use of non-vitamin K antagonist oral anticoagulants (NOACs), real-world data on time to discontinuation and time to re-initiation of the NOAC treatment are still scarce.

Purpose
To identify patterns of time to discontinuation as well as time to re-initiation of NOACs in patients with NVAF during the first year of treatment in UK primary care.

Methods
This population-based retrospective cohort study included 11,481 patients with NVAF, aged 18 and above, enrolled in The Health Improvement Network (THIN) with at least 1 year of follow-up after first recorded prescription of apixaban, dabigatran, or rivaroxaban between Jan 2012 to Dec 2016, and received two or more prescriptions of index NOAC. Discontinuation was defined as an interval greater than 30 days between the end of supply of the index NOAC and the date of the next prescription of the index NOAC. Discontinuers were further categorized as switchers, re-initiators or non-re-initiators. Re-initiators were patients who re-started OAC therapy after they discontinued treatment. Proportion of patients who discontinued NOAC treatment as well as mean duration (months) on treatment was calculated.

Results
The majority of patients were continuous users of their initial NOAC; discontinuation within the first year of treatment accounted for 26.1% of the apixaban cohort, 40.0% of the dabigatran cohort, and 29.6% of the rivaroxaban cohort.
Time to discontinuation: Among discontinuers, the mean time patient stayed on initial treatment was the least for dabigatran (4.5 months), followed by apixaban (4.7 months) and highest for rivaroxaban (4.9 months). Discontinuers who did not later reinitiate any OAC therapy had a slightly longer time to discontinuation (mean 5.5 months) than those who later reinitiated OAC therapy (either on the same NOAC, a different NOAC or VKA; mean 4.6 months), or who switched treatment (4.0 months).
Time to re-initiation: Among OAC reinitiators, no difference was seen in the time to re-initiation between NOACs (apixaban – 1.9 months, dabigatran – 2.1 months, and rivaroxaban – 2.0 months.

Conclusion
The proportion of discontinuation among new users of NOAC with NVAF in the first year was 30%. Average time on treatment for switchers, re-initiators and those who completely discontinued shows that such activities occurs around 4–5 months after initiating NOAC treatment, which is when further monitoring might be required. Once discontinued, re-initiation of NOAC treatment on average took 55–65 days.

Acknowledgement/Funding
The study is funded by Bayer AG