Abstract 15084: A Retrospective Analysis of Atrial Fibrillation Patients Aged 80 Years and Older Prescribed a Low-dose Non-vitamin K Antagonist Anticoagulant

Background: The very elderly and those receiving low doses of the direct-acting oral anticoagulants (DOACs) were underrepresented in trials leading to the approval of Apixaban 2.5 mgs BID (A), Rivaroxaban 15mgs daily (R) and Edoxaban 30 mgs daily (E). Approval of dabigatran 75mgs BID (D) was based entirely on pharmacokinetic studies. Methods: Retrospective analysis of the electronic medical record of a multi-disciplinary practice of 396,064 patients between 1/1/11 (when first DOAC available) and 5/31/17. Results: 9,446 patients had Atrial Fibrillation (AF), with 2,660 prescribed a DOAC and 846 at the low dose with 514 ≥ 80 yrs (range 80 – 98) with a mean CHA 2 DS 2 -VASc score of 4.5, which did not differ between patients prescribed D, R or A (p = 0.66 by ANOVA). Fifty-three patients received D, first used on 2/26/11, 223 R, first used on 12/15/11, and 236 A, first used on 6/19/12, and one patient received E. Among 28 baseline variables there were no clinically relevant differences among D, R, and A. All outcomes were reported as time to first event. All-cause mortality, n = 5 (5.5%/yr) for D, n =15 (4.2%) for R, and n = 23 (9.5%) for A, p = 0.031 by log rank test (with A > R by pairwise log-rank, p = 0.013). Major bleeding n = 13 (14.3%/yr) for D, n = 50 (14.1%) for R, and n = 22 (9.1%) for A, p = 0.048 by log rank test (with A < R, p = 0.017). Intracranial bleeding n = 2 (2.2%/yr) for D, n = 6 (1.7%) for R, and n = 2 (0.8%) for A, p = 0.53. There were 7 ischemic strokes or systemic embolic events (SSE) in total (1.1%/yr): D, R, and A (p = 0.94). Comparisons involving D may be underpowered. 245 patients (47.7%) remained on their prescribed drug without an event for the observation period (p = 0.55). Conclusion: D, R and A were well tolerated in patients ≥ 80 yrs, with low SSE and intracranial bleed rates. Major bleeds were the most frequent outcome, lowest in patients prescribed A. A had a higher all-cause mortality.

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Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney Disease

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.06430518 ◽

2018 ◽

Vol 14 (1) ◽

pp. 125-136 ◽

Cited By ~ 5

Author(s):

Katherine G. Garlo ◽

David J.R. Steele ◽

Sagar U. Nigwekar ◽

Kevin E. Chan

Keyword(s):

Atrial Fibrillation ◽

Controlled Trial ◽

Clinical Care ◽

Oral Anticoagulants ◽

Contemporary Literature ◽

Clinical Equipoise ◽

Pharmacokinetic Studies ◽

Randomized Controlled ◽

Direct Acting

Patients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25–30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.

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P4753Impact of renal function on bleeding risk in patients with non-valvular atrial fibrillation treated with direct oral anticoagulants: Subanalysis of the DIRECT registry

European Heart Journal ◽

10.1093/eurheartj/ehz745.1129 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Hirata ◽

Y Sotomi ◽

T Kobayashi ◽

R Amiya ◽

A Hirayama ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Renal Dysfunction ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Rank Test ◽

Log Rank Test ◽

Kaplan Meier

Abstract Background Renal dysfunction is one of the high bleeding risk factors in patients with atrial fibrillation as presented in the HAS-BLED score. The impact of renal function on bleeding risk is, however, still to be investigated in the era of direct oral anticoagulants (DOAC). Methods We conducted a single-center prospective observational registry of NVAF patients with DOACs: the DIRECT registry (UMINehz745.112933283). All patients with NVAF (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from 2011 to 2017 were enrolled (71.6±10.8 years, mean follow-up duration: 407.2±388.3 days). In the present substudy, all patients were stratified by renal function. Creatinine clearance (CCr) was estimated with the Cockcroft-Gault equations with available creatinine at baseline. Patients were divided into 4 groups based on CCr. (CCr>80, CCr50–80, CCr30–50, and CCr<30). The primary endpoint was major bleeding according to the ISTH criteria. Clinical endpoints were compared between the groups (Kaplan-Meier analysis, Log-rank test). The influence of DOAC type in patients with renal dysfunction was also assessed for the primary endpoints of major bleeding. Results Kaplan-Meier estimated 2-year major bleeding rate significantly increased as renal function decreased (CCr>80 2.5%, CCr50–80 4.2%, CCr30–50 4.2%, CCr<30 7.8%, Log-rank test p<0.001). However, in patients with apixaban (low CCr 59.6±25.9ml), major bleeding does not appear to increase as renal function decreased.(CCr >80 9.2%, CCr 50–80 8.0%, CCr 30–50 10.3%, CCr<30 7.3%, Log-rank test p=0.97). Kaplan-Meier Analysis Conclusions Renal dysfunction increased bleeding risks in NVAS patients with DOACs. Apixaban might be safely used for patients with renal dysfunction.

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Prophylactic anticoagulation in patients with glioblastoma or brain metastases and atrial fibrillation: an increased risk for intracranial hemorrhage?

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03716-8 ◽

2021 ◽

Author(s):

Sina Burth ◽

Mona Ohmann ◽

Dorothea Kronsteiner ◽

Meinhard Kieser ◽

Sarah Löw ◽

...

Keyword(s):

Atrial Fibrillation ◽

Brain Metastases ◽

Intracranial Hemorrhage ◽

Stroke Risk ◽

Oral Anticoagulants ◽

Rank Test ◽

Log Rank Test ◽

Increased Risk ◽

Prophylactic Anticoagulation

Abstract Purpose Patients with glioblastoma (GBM) or brain metastases (MET) and atrial fibrillation (AF) might be at an increased risk of intracranial hemorrhage (ICH) due to anticoagulation (AC). Our aim was to assess this risk. Methods Our institution’s database (from 2005 to 2017) was screened for patients with GBM or MET and AF with an indication for AC according to their CHA2DS2VASc stroke risk score (≥ 2). Required follow-up was at least 3 months. AC was either performed with heparins, phenprocoumon or non-Vitamin K antagonist oral anticoagulants. Applying the propensity score approach, patient cohorts (matched according to primary tumor, age, sex) were generated (GBM [or MET] with AF ± AC, GBM [or MET] without AF/AC, no GBM [or MET] but AF on AC). ICH was defined as clinical deterioration caused by new blood on imaging. A log rank test was performed to compare the risk for ICH between the three groups. Results In total, 104 patients were identified of which 49 with GBM (37% on AC) and 37 with MET (46% on AC) were successfully matched. Median follow up was 8.6 and 7.2 months, respectively. ICH occurred in 10.2% of GBM + AF and 12.2% GBM-AF, whereas 8% of patients with AF on AC suffered ICH (p = 0.076). 13.5% of patients with MET + AF had ICHs, in the controls it was 16% for MET-AF and 8% for AF on AC (p = 0.11). Conclusion AC did not seem to influence the incidence of ICH in patients with glioblastoma or brain metastases within follow up of just under 9 months.

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Comparison of de novo and upgrade to resynchronization therapy: a propensity-score matched analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.0795 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Brandao ◽

J Goncalves Almeida ◽

J Monteiro ◽

F Montenegro Sa ◽

P Fonseca ◽

...

Keyword(s):

New York ◽

Propensity Score ◽

De Novo ◽

Heart Association ◽

Rank Test ◽

Resynchronization Therapy ◽

Cardiac Events ◽

Systolic Volume ◽

Log Rank Test ◽

All Cause Mortality

Abstract Background Upgrade to resynchronization therapy (CRT) from conventional pacemaker (P) or defibrillator (D) is common practice in Europe. However, guidelines (GL) are discordant: Pacing GL give a class I recommendation, while Heart Failure (HF) GL provide a class IIb indication. Previous studies suggested worse outcomes in upgraded patients (pts). Aim To compare response rate and clinical outcomes in a cohort of pts receiving de novo or upgrade to CRT. Methods Single-center retrospective study of consecutive pts submitted to CRT implantation (2007–2017). Major adverse cardiac events (MACE) included HF hospitalization (HHF) or all-cause mortality. Clinical response was defined as New York Heart Association class improvement without MACE in the first year of follow-up (FU). Left ventricle end-systolic volume reduction of >15% denoted echocardiographic (echo) response. Survival analysis with Kaplan-Meier method and Log-rank test was performed. Propensity-score matching (PSM) analysis was made to adjust for possible confounder variables. Results 230 CRT recipients (70.9% male, mean age 67±11 years, 71.5% non-ischemic cardiomyopathy, 39.6% CRT-P) were included, of whom 46 (20%) underwent an upgrade. Upgraded pts were older (69.8 vs 65.9 years, p=0.015), with higher rates of permanent atrial fibrillation (37.0% vs 12.7%, p=0.001), moderate to severe valve disease (45.7% vs 22.3%, p=0.002), chronic kidney disease (37.0% vs 17.2%, p=0.005) and treatment with mineralocorticoid receptor antagonists (79.1% vs 52.0%, p=0.002). They were more likely to receive CRT-P (65.2% vs 33.2%, p<0.001) and CRT-D were more often implanted for secondary prevention (60.0% vs 17.9%, p=0.001). No differences emerged in procedural complications, clinical (74.4% vs 71.4%, p=0.712) or echo (66.7% vs 69.7%, p=0.822) response rates. During a median FU of 3±4 years, all-cause mortality was similar among groups (Log Rank test, p=0.522, unadjusted hazard ratio [HR] 1.25, confidence interval [CI] 95% 0.62–2.49, p=0.534). There was a statistical tendency for higher MACE rate in the upgrade group (Log Rank test, p=0.064, HR 1.66, CI 95% 0.95–2,91, p=0.076). No differences were found in lead dislodgement (10.9% vs 7.1%, p=0.368) or endocarditis (2.2% vs 4.3%, p=0.692) rates. PSM analysis identified 88 matched pairs (46 upgrade/42 de novo pts). In this cohort, all-cause mortality (Log Rank test, p=0.77, HR 0.89, CI 95% 0.39–2.03, p=0.78) and MACE (Log Rank test, p=0.36, HR 1.38, CI 95% 0.68–2.81, p=0.37) were comparable between groups [graph no. 1]. Conclusion Upgrade to CRT was similar to de novo implantation in terms of complications and clinical and echo response, in this cohort. The risk for MACE and mortality was also comparable. Graph 1 Funding Acknowledgement Type of funding source: None

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Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program

European Heart Journal ◽

10.1093/ehjci/ehaa946.0663 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Yamashita ◽

C.C Wang ◽

Y.-H Kim ◽

R De Caterina ◽

P Kirchhof ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Major Bleeding ◽

Intracranial Haemorrhage ◽

Clinical Care ◽

Oral Anticoagulants ◽

Clinical Event ◽

Funding Source ◽

Private Company ◽

All Cause Mortality

Abstract Background The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest. Purpose Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups. Results Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality. Conclusion Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo

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AB0621 TOLERABILITY AND SAFETY OF ACETYLSALICYLIC ACID IN PATIENTS WITH SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6335 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1606.2-1606

Author(s):

L. Verardi ◽

E. De Lorenzis ◽

G. Natalello ◽

L. Gigante ◽

U. La Porta ◽

...

Keyword(s):

Systemic Sclerosis ◽

Adverse Events ◽

Low Dose ◽

Disease Duration ◽

Rank Test ◽

Digital Ulcers ◽

Log Rank Test ◽

Gastrointestinal Intolerance ◽

Male Sex ◽

Observation Period

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

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306 The Changing Face of Stroke in the DOAC Era

Age and Ageing ◽

10.1093/ageing/afz103.196 ◽

2019 ◽

Vol 48 (Supplement_3) ◽

pp. iii17-iii65

Author(s):

Recie Davern ◽

Helena Hobbs ◽

Hannah Murugan ◽

Paul Cotter

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulants ◽

P Value ◽

Stroke Management ◽

Medicines Management ◽

First Line ◽

Stroke Registry ◽

Multiple Factors ◽

Direct Acting ◽

Anticoagulated Patients

Abstract Background Patients prescribed oral anticoagulants (OAC) for atrial fibrillation (AF) can still present with stroke. The mechanism for stroke in these patients can be due to multiple factors including subtherapeutic dosing and non-compliance. With the increasing use of direct-acting OACs (DOACs) in favour of warfarin, it is unclear if the incidence of stroke in those already taking OAC has reduced. Methods Data was extracted from our unit’s stroke registry, a prospectively maintained database, for patients who presented with stroke while receiving OAC for AF from 2013 to 2017. Type of OAC, type of stroke, OAC dosing at time of event including non-compliance, stroke management and outcome were recorded. Results 67 patients were included for analysis, with 55 ischaemic and 12 haemorrhagic strokes. 52 patients were receiving warfarin at the time of their stroke vs. 15 receiving DOACs. 33/55 (60%) of ischaemic strokes occurred in patients taking warfarin with a sub-therapeutic INR. In 3/55 (5%) of ischaemic strokes, the OAC was held for a procedure while in 6/55 cases (11%) the OAC had been stopped for another reasons e.g. bleeding. 5/55 (7%) were due to non-compliance. 1 ischaemic stroke was due to under-dosing of a DOAC (dabigatran). 16 strokes were recorded in 2013 for patients prescribed OAC vs. 3 in 2017. Overall the number of ischaemic strokes due to subtherapeutic OAC decreased from 14 in 2013 to 1 in 2017 (p value 0.06). Conclusion The majority of strokes occurring in anticoagulated patients are related to warfarin use. We observed an almost significant reduction in the proportion of ischaemic strokes due to under-dosing of OAC over the study period. Warfarin continues to be recommended as the first line anticoagulant for stroke prevention in atrial fibrillation by the HSE Medicines Management Programme, a decision which we would argue warrants review.

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