How effective are dose-adjusted warfarin and aspirin for the prevention of stroke in patients with chronic atrial fibrillation?

SummaryThe objective of this study was to evaluate the rate of stroke associated with aspirin and warfarin in routine clinical practice. The study included patients aged 40+ with chronic atrial fibrillation (cAF) registered in the UK General Practice Research Database. The outcome was the rate of stroke during current, past and no use of aspirin and warfarin. The study included 51,807 cAF patients. There was no difference in the rate of stroke between current and past use of aspirin (relative rate [RR]=1.04 [95% confidence interval (CI) 0.94 – 1.15]), while the rate of stroke was reduced during current warfarin use compared to past use (RR=0.62 [95% CI 0.54 – 0.71]). For warfarin, a pattern of lower rates of stroke during current exposure and higher rates with past exposure was seen only in patients treated for at least 6–12 months. For aspirin, no changes in the rates of stroke were observed with discontinuation of aspirin. The effectiveness of warfarin was dependent on the level of anticoagulation, with optimal risk reduction occurring within the recommended international normalised ratio (INR) range of 2.0 to 3.0. The proportion of patients achieving a stable INR within the target therapeutic range was at its lowest during the first three months of warfarin treatment. In conclusion, the results of this study support the effectiveness of warfarin treatment to reduce the rate of stroke in cAF patients in the general clinical practice setting, however the risk reduction is lower than that reported in clinical trials.

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

Thrombosis and Haemostasis ◽

10.1160/th11-05-0353 ◽

2011 ◽

Vol 106 (11) ◽

pp. 968-977 ◽

Cited By ~ 246

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.

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Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on “real-world” data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database

Clinical Epidemiology ◽

10.2147/clep.s164112 ◽

2018 ◽

Vol Volume 10 ◽

pp. 1417-1431 ◽

Cited By ~ 7

Author(s):

Sara Khalid ◽

Sara Calderón-Larrañaga ◽

Samuel Hawley ◽

Sanni Ali ◽

Andrew Judge ◽

...

Keyword(s):

Clinical Practice ◽

Real World ◽

Meta Analysis ◽

Practice Research ◽

Research Database ◽

Matched Cohort ◽

The Uk

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Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: Cohort study using data from the UK General Practice Research Database

British Journal of Clinical Pharmacology ◽

10.1111/j.1365-2125.2005.02370.x ◽

2005 ◽

Vol 60 (1) ◽

pp. 76-82 ◽

Cited By ~ 78

Author(s):

Stefan Russmann ◽

James A. Kaye ◽

Susan S. Jick ◽

Hershel Jick

Keyword(s):

General Practice ◽

Cohort Study ◽

Liver Disease ◽

General Practice Research Database ◽

Practice Research ◽

Cholestatic Liver Disease ◽

Research Database ◽

Prescribing Habits ◽

Using Data ◽

The Uk

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

Thrombosis and Haemostasis ◽

10.1160/th05-03-0166 ◽

2005 ◽

Vol 94 (09) ◽

pp. 537-543 ◽

Cited By ~ 38

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.

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