The concurrent use of antithrombotic therapies and the risk of bleeding in patients with atrial fibrillation

2013 ◽  
Vol 109 (03) ◽  
pp. 431-439 ◽  
Author(s):  
Laurent Azoulay ◽  
Sophie Dell’Aniello ◽  
Teresa Simon ◽  
Christel Renoux ◽  
Samy Suissa
Keyword(s):  
Atrial Fibrillation ◽  
Triple Therapy ◽  
Large Population ◽  
Population Based ◽  
Practice Research ◽  
Control Analysis ◽  
Research Database ◽  
Risk Of Bleeding ◽  
Concurrent Use ◽  
Increased Risk

SummaryPatients with atrial fibrillation (AF) often receive, in addition to warfarin, antithrombotic drugs to manage other comorbid conditions. To date, few population-based studies have quantified the bleeding risk associated with the concurrent use of these therapies. The United Kingdom General Practice Research Database was used to identify a cohort of 70,760 patients newly-diagnosed with AF between 1993 and 2008. A nested case-control analysis was conducted within that cohort, and conditional logistic regression was used to estimate adjusted rate ratios (RRs) of bleeding associated with current use of warfarin, aspirin, and clopidogrel in single therapy, as well as in dual and triple therapy, as compared with non-use of any therapy. A total of 10,850 patients experienced a bleeding event during follow-up. In single therapy, warfarin was associated with the highest increased risk (RR: 2.08, 95% confidence interval [CI]: 1.95–2.23), followed by clopidogrel (RR: 1.57, 95% CI: 1.37–1.81) and aspirin (RR: 1.25, 95% CI: 1.17–1.34). In dual therapy, combinations containing warfarin were associated with a higher increased risk (warfarin-aspirin: RR: 2.87, 95% CI: 2.58–3.19, and warfarin-clopidogrel: RR: 2.74, 95% CI: 2.14–3.51), than those not containing warfarin (aspirin-clopidogrel: RR: 1.68, 95% CI: 1.44–1.97). Triple therapy of warfarin-aspirin-clopidogrel was associated with the highest increased risk (RR: 3.75, 95% CI: 2.71–5.19). This large population-based study suggests that while all antithrombotic therapies are associated with an elevated risk of bleeding, the risks increase in an additive fashion with dual and triple therapy, particularly in combinations containing warfarin.

scholarly journals Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin

2005 ◽  
Vol 94 (09) ◽  
pp. 537-543 ◽  
Author(s):  
Jennifer Hollowell ◽  
Christoph R. Meier ◽  
Walter E. Haefeli ◽  
Christiane Gasse
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Conditional Logistic Regression ◽  
General Practice Research Database ◽  
Practice Research ◽  
Control Analysis ◽  
Research Database ◽  
Nonvalvular Atrial Fibrillation ◽  
Increased Risk

SummaryAlthough drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40–84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (>3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took ≥1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used >4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4–8.5) for the risk of serious bleeding in patients treated with warfarin and ≥1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1–18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.

Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients

2011 ◽  
Vol 106 (11) ◽  
pp. 968-977 ◽  
Author(s):  
Arlene Gallagher ◽  
Efrosini Setakis ◽  
Jonathan Plumb ◽  
Andreas Clemens ◽  
Tjeerd-Pieter van Staa
Keyword(s):  
Atrial Fibrillation ◽  
Therapeutic Range ◽  
Cox Regression ◽  
Relative Rate ◽  
General Practice Research Database ◽  
Practice Research ◽  
Study Cohort ◽  
Research Database ◽  
Increased Risk ◽  
The Uk

SummaryAtrial fibrillation (AF) carries an increased risk of ischaemic stroke, and oral anticoagulation with warfarin can reduce this risk. The objective of this study was to evaluate the association between time in therapeutic International Normalised Ratio (INR) range when receiving warfarin and the risk of stroke and mortality. The study cohort included AF patients aged 40 years and older included in the UK General Practice Research Database. For patients treated with warfarin we computed the percentage of follow-up time spent within therapeutic range. Cox regression was used to assess the association between INR and outcomes while controlling for patient demographics, health status and concomitant medication. The study population included 27,458 warfarintreated (with at least 3 INR measurements) and 10,449 patients not treated with antithrombotic therapy. Overall the warfarin users spent 63% of their time within therapeutic range (TTR). This percentage did not vary substantially by age, sex and CHA2DS2-VASc score. Patients who spent at least 70% of time within therapeutic range had a 79% reduced risk of stroke compared to patients with ≤30% of time in range (adjusted relative rate of 0.21; 95% confidence interval 0.18–0.25). Mortality rates were also significantly lower with at least 70% of time spent within therapeutic range. In conclusion, good anticoagulation control was associated with a reduction in the risk of stroke.

scholarly journals Antihypertensive Medications and COVID-19 Diagnosis and Mortality: Population-based Case-Control Analysis in the United Kingdom

2020 ◽  
Author(s):  
Emma Rezel-Potts ◽  
Abdel Douiri ◽  
Phil J Chowienczyk ◽  
Martin C Gulliford
Keyword(s):  
Antihypertensive Therapy ◽  
Population Based ◽  
Case Control ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Control Analysis ◽  
Antihypertensive Medications ◽  
Lower Odds ◽  
Healthcare Seeking ◽  
Increased Risk

Objectives: To evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare seeking behaviour. Design: A population-based case control study with additional cohort analysis. Setting: Primary care patients from the UK Clinical Practice Research Datalink (CPRD). Participants: 16 866 patients with COVID-19 events in the CPRD from 29th January to June 25th 2020 and 70 137 matched controls. Main outcome measures: We explored associations between COVID-19 diagnosis and prescriptions for angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). We evaluated all-cause mortality among COVID-19 cases. Analyses were adjusted for covariates and consultation frequency. Results: In covariate adjusted analyses, ACEIs were associated with lower odds of COVID-19 diagnosis (0.82, 95% confidence interval 0.77 to 0.88) as were ARBs, 0.87 (0.80 to 0.95) with little attenuation from adjustment for consultation frequency. In fully adjusted analyses, C and D were also associated with lower odds of COVID-19. Increased odds of COVID-19 for B (1.19, 1.12 to 1.26), were attenuated after adjustment for consultation frequency (1.01, 0.95 to 1.08). In adjusted analyses, patients treated with ACEIs or ARBs had similar mortality to patients treated with classes B, C, D or O (1.00, 0.83 to 1.20) or patients receiving no antihypertensive therapy (0.99, 0.83 to 1.18). Conclusions: Associations were sensitive to adjustment for confounding and healthcare seeking, but there was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.

Consensus Document: Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting

2011 ◽  
Vol 106 (10) ◽  
pp. 571-584 ◽  
Author(s):  
John Eikelboom ◽  
Peter Berger ◽  
David Holmes ◽  
Deepak Bhatt ◽  
Richard Becker ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Risk Assessment ◽  
Triple Therapy ◽  
Major Bleeding ◽  
National Guidelines ◽  
Risk Of Bleeding ◽  
Consensus Document ◽  
Increased Risk ◽  
Optimal Regimen ◽  
Adequate Data

SummaryThe optimal regimen of the anticoagulant and antiplatelet therapies in patients with atrial fibrillation who have had a coronary stent is unclear. It is well recognised that “triple therapy” with aspirin, clopidogrel, and warfarin is associated with an increased risk of bleeding. National guidelines have not made specific recommendations given the lack of adequate data. In choosing the best antithrombotic options for a patient, consideration needs to be given to the risks of stroke, stent thrombosis and major bleeding. This document describes these risks, provides specific recommendations concerning vascular access, stent choice, concomitant use of proton-pump inhibitors and the use and duration of triple therapy following stent placement based upon the risk assessment.

scholarly journals Cross-Sectional Associations between Homoarginine, Intermediate Phenotypes, and Atrial Fibrillation in the Community—The Gutenberg Health Study

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 86 ◽  
Author(s):  
Christoph Niekamp ◽  
Dorothee Atzler ◽  
Francisco Ojeda ◽  
Christoph Sinning ◽  
Karl Lackner ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Large Population ◽  
Population Based ◽  
Health Study ◽  
Cross Sectional ◽  
Standard Deviation Increase ◽  
Gutenberg Health Study ◽  
Intermediate Phenotypes ◽  
Increased Risk

Homoarginine has come into the focus of interest as a biomarker for cardiovascular disease. Atrial fibrillation (AF) causes a substantial increase in morbidity and mortality. Whether circulating homoarginine is associated with occurrence or persistence of AF and may serve as a new predictive biomarker remains unknown. We measured plasma levels of homoarginine in the population-based Gutenberg health study (3761 patients included, of them 51.7% males), mean age 55.6 ± 10.9 years-old. Associations between homoarginine and intermediate electrocardiographic and echocardiographic phenotypes and manifest AF were examined. Patients with AF (124 patients, of them 73.4% males) had a mean age 64.8 ± 8.6 years-old compared to a mean age of 55.3 ± 10.9 in the population without AF (p-value < 0.001) and showed a less beneficial risk factor profile. The median homoarginine levels in individuals with and without AF were 1.9 μmol/L (interquartile range (IQR) 1.5–2.5) and 2.0 μmol/L (IQR 1.5–2.5), respectively, p = 0.56. In multivariable-adjusted regression analyses homoarginine was not statistically significantly related to electrocardiographic variables. Among echocardiographic variables beta per standard deviation increase was −0.12 (95% confidence interval (CI) −0.23–(−0.02); p = 0.024) for left atrial area and −0.01 (95% CI −0.02–(−0.003); p = 0.013) for E/A ratio. The odds ratio between homoarginine and AF was 0.91 (95% CI 0.70–1.16; p = 0.45). In our large, population-based cross-sectional study, we did not find statistically significant correlations between lower homoarginine levels and occurrence or persistence of AF or most standard electrocardiographic phenotypes, but some moderate inverse associations with echocardiographic left atrial size and E/A. Homoarginine may not represent a strong biomarker to identify individuals at increased risk for AF. Further investigations will be needed to elucidate the role of homoarginine and cardiac function.

Risk of cataract and glaucoma in patients with multiple sclerosis

2011 ◽  
Vol 18 (5) ◽  
pp. 628-638 ◽  
Author(s):  
Marloes T Bazelier ◽  
Sigrid Mueller-Schotte ◽  
Hubert GM Leufkens ◽  
Bernard MJ Uitdehaag ◽  
Tjeerd van Staa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
General Practice Research Database ◽  
Population Based ◽  
Practice Research ◽  
Research Database ◽  
Hazard Ratios ◽  
Increased Risk ◽  
History Of ◽  
The Uk ◽  
Hospital Registry

Background: The aim of the study was to evaluate whether multiple sclerosis (MS) is associated with risk of cataract or glaucoma. Methods: We conducted a population-based cohort study utilizing the UK General Practice Research Database (1987–2009) linked to the national hospital registry of England (1997–2008). Incident MS patients (5576 cases) were identified and each was matched to six patients without MS (controls) by age, gender, and practice. Cox proportional hazard models were used to estimate hazard ratios (HRs) of incident cataract and glaucoma in MS. Time-dependent adjustments were made for age, history of diseases and drug use. Results: MS patients had no overall increased risk of cataract, adjusted (adj.) HR 1.15 (95% CI 0.94–1.41) or glaucoma, adj. HR 1.02 (95% CI 0.78–1.33). Risk of cataract (adj. HR 2.45 (95% CI 1.56–3.86)) and glaucoma (adj. HR 1.70 (95% CI 1.01–2.86)) was significantly greater in patients < 50 years, particularly in men < 50 years: cataract, adj. HR 4.23 (95% CI 2.22–8.05) and glaucoma, adj. HR 2.76 (95% CI 1.28–5.93). Conclusion: This is the first study which showed that the risk of cataract and glaucoma is elevated in MS patients younger than 50 years, particularly men.

Patterns of use of tamoxifen and aromatase inhibitors: A population-based observational study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 556-556
Author(s):  
L. Huiart ◽  
S. Dell'Aniello ◽  
S. Suissa
Keyword(s):  
Aromatase Inhibitors ◽  
Large Population ◽  
General Practice Research Database ◽  
Real Life ◽  
Population Based ◽  
Practice Research ◽  
First Year ◽  
Research Database ◽  
Patterns Of Use ◽  
Few Data

556 Background: Few data are available outside clinical trials on the use of aromatase inhibitors (AI) as adjuvant treatment for early breast cancer (BC). We therefore used a large population-based database to describe patterns of use of AI over time, in comparison with tamoxifen, as well as switches between these regimens. Methods: We identified 13,479 women treated for BC with tamoxifen, anastrazole, letrozole, or exemestane between 1998 and June 2008 in the UK General Practice Research Database (GPRD). Patients were followed from their first prescription for 5 years or until recurrence, death, switch to another treatment or occurrence of a major thromboembolic or uterine event. Results: Mean age at cohort entry was 62 years (SD=14.0) in the tamoxifen group (n=10,806) and 70.8 (SD = 12.4) in the AI group (n=2,673). Overall, in the first year of treatment 88.8% of patients had prescriptions covering more than 80% of the year (88.3% and 90.8% in tamoxifen and in AI group respectively). Table 1 describes prescriptions covering less than 80% of the days for each year of treatment in 3 subgroups. Among women started on AI therapy diagnosed with BC after 2006, 9.6% switched treatment. Half of them switched from one AI to another AI, the other half switched from AI to tamoxifen. Switches occurred within the first year of treatment in 76% of cases. Among women over 50 years of age who started a tamoxifen therapy after 2000, 31% of women switched to AI in the course of the study, of which 12% within the first year of treatment (11.1% and 13.7% for women diagnosed in 2000–2004 and after 2005 respectively). Conclusions: The real-life patterns of use of tamoxifen and AI therapy demonstrate high rates of adherence. However, the relatively high percentage of switchers among AI users is suggestive of an association with side-effects. [Table: see text] No significant financial relationships to disclose.

Naxos study: risk of bleeding with oral anticoagulants in non-valvular atrial fibrillation patients in France

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Danchin ◽  
P.G Steg ◽  
O Hanon ◽  
I Mahe ◽  
B Falissard ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Lower Risk ◽  
Propensity Scores ◽  
Oral Anticoagulants ◽  
Population Based ◽  
Intestinal Bleeding ◽  
Funding Source ◽  
Risk Of Bleeding ◽  
Increased Risk

Abstract Background In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulants reduce the risk of stroke and systemic embolism, at the expense of an increased risk of bleeding. Purpose To compare the risk of bleeding and sites of bleeding according to the type of oral anticoagulant used in NVAF patients. Methods NAXOS is a population-based, historical cohort study including all patients aged ≥18 years with NVAF and newly initiating one of the OACs available in France between 2014 and 2016, aiming to compare safety, effectiveness, and all-cause mortality, according to the type of oral anticoagulant used. The French national health insurance reimbursement database, cross-linked with the hospitalisation database and civil status registry (SNIIRAM) was used to identify first users of oral anticoagulants and outcomes over their follow-up. Major bleeding events were identified through main diagnoses of hospital stays, with a specific focus on bleeding site. Apixaban was used as the reference treatment. Analyses were performed on crude data and with adjustment on propensity scores calculated separately for each of the comparators (VKAs, rivaroxaban and dabigatran). Results Overall, 321,501 NVAF patients were included: 87,565 (27.2%), 112,628 (35.0%), 100,063 (31.1%), and 21,245 (6.6%) initiated apixaban, VKAs, rivaroxaban, and dabigatran, respectively. The crude risks of intracranial bleeding were 0.45 [0.40–0.50], 1.23 [1.16–1.30], 0.48 [0.44–0.53], and 0.26 [0.19–0.34] per 100 patient-year, for apixaban, VKA, rivaroxaban, and dabigatran, respectively. The respective figures for gastro-intestinal bleeding were: 0.67 [0.61–0.74], 1.73 [1.64–1.81], 1.01 [0.94–1.08], 1.02 [0.89–1.17]; and those for non-intracranial and non-gastro-intestinal but other bleeding were: 0.84 [0.78–0.92], 2.22 [2.13–2.32], 1.24 [1.17–1.31] and 0.71 [0.60–0.84]. After adjustment on propensity-scores, patients initiating apixaban were at a lower risk of all major bleeding vs. VKA, rivaroxaban and dabigatran (HR=0.49 [0.46–0.52], 0.63 [0.58–0.67]) and 0.85 [0.76–0.95]). Apixaban was associated with a decreased risk of intracranial bleeding compared with VKAs (HR=0.46 [0.40–0.53]) and rivaroxaban (HR=0.80 [0.69–0.93]), and an increased risk compared with dabigatran (HR=1.53 [1.12–2.07]). The risk of gastro-intestinal bleeding was lower with apixaban than with VKAs (HR=0.57; [0.55–0.59]), rivaroxaban (HR=0.59; [0.52–0.66]), and dabigatran (HR=0.57; 0.48–0.68]). For other bleedings, apixaban was associated with a lower risk compared with VKAs (HR=0.47; [0.43–0.52]), and rivaroxaban (HR=0.59; [0.53–0.66]), and with a similar risk compared with dabigatran (HR=1.01; [0.84–1.23]). Conclusion In this large, real-world, population-based cohort, apixaban was associated with a lower risk of all types of bleedings requiring hospitalisation, compared with vitamin K antagonists. Differences between direct oral anticoagulants were also observed. Results of the comparative analyses Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bristol-Myers Squibb, Pfizer

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