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A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case-control study.

ABSTRACT: As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993-2008 was conducted within the United Kingdom General Practice Research Database. A nested case-control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year) was calculated by subtracting the ischemic stroke rate (prevented by therapy) from the intracranial hemorrhage (ICH) rate (increased by therapy).The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73). However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54) and above (-0.49, 95% CI: -1.13, 0.15) therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (-0.07, 95% CI: -0.22, 0.08), though it was seen in certain subgroups.Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.

SUBMITTER: Azoulay L

PROVIDER: S-EPMC3444325 | biostudies-other | 2012 Jun

REPOSITORIES: biostudies-other

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A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case-control study.

Azoulay Laurent L Dell'Aniello Sophie S Simon Teresa A TA Langleben David D Renoux Christel C Suissa Samy S

BMC cardiovascular disorders 20120626

<h4>Background</h4>As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).<h4>Methods</h4>A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993-2008 was conducted within the United Kingdom General Practice Research Datab ...[more]

PMID: 22734842

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Project description:BackgroundGuidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage.ObjectiveTo quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation.DesignMixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003.SettingAn integrated health care delivery system.Patients13 559 adults with nonvalvular atrial fibrillation.MeasurementsWarfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism.ResultsPatients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used.LimitationsResidual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable.ConclusionExpected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation.Primary funding sourceNational Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

Project description:Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population.We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF.Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ? 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ? 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61.9% in 2012 in the latter (P for trend for both, < .005). In the overall cohort, the annual stroke rate was approximately 6% and the annual major bleeding rate was about 1%. Compared with nonantithrombotic therapy, the hazard ratio for ischemic stroke was 0.68 (95% CI, 0.39-1.18) for aspirin and 1.39 (0.54-3.59) for warfarin.Aspirin use increased among Chinese patients newly diagnosed with AF, with no relationship to the patient's stroke or bleeding risk. Warfarin use was very low. Given the health-care burden of AF and its complications, our study has major implications for health-care systems in non-Western countries, given the global burden of this common arrhythmia.

Project description:Background The PROTECT-AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trials demonstrated noninferiority of left atrial appendage closure (LAAC) to warfarin for the composite end point of stroke, systemic embolism, or cardiovascular death. This study aims to quantify the net clinical benefit (NCB) of LAAC versus warfarin, accounting for differences in clinical impact of different event types. Methods and Results We performed a post hoc analysis of the PROTECT-AF and PREVAIL trials, which randomized atrial fibrillation patients to LAAC or warfarin in a 2:1 fashion. The trials enrolled patients in the United States and Europe between 2005 and 2012 with paroxysmal, persistent, or permanent atrial fibrillation and CHADS2 risk scores ≥1. Relative to an index weight for death (1.0), events were assigned weights based on their disabling effect: (1) stroke event weights were based on modified Rankin scores in the base case analyses, and (2) major bleed (0.05) and pericardial effusion (0.05). NCB was calculated as the sum of weight-adjusted events per 100 patient-years. Among 1114 randomized subjects, the NCB of LAAC was 1.42% per year (95% CI 0.01-2.82, P=0.04) and a relative risk of 0.74 (95% CI 0.56-1.00). NCB point estimates favored warfarin early in follow-up, but trended in favor of LAAC after 1 to 2 years. The benefit of LAAC was preserved across subgroups, with particular benefit observed in the subgroup of prior stroke and without diabetes mellitus. Conclusions This analysis demonstrates long-term NCB of LAAC with Watchman over warfarin therapy, as the upfront risk of periprocedural events is counterbalanced over time by reduced bleeding events and mortality. Clinical Trial Registration UR: http://www.clinicaltrials.gov. Unique identifiers: NCT01182441 and NCT00129545.

Project description:Currently, the potential risk of atrial fibrillation associated with antihyperglycemic drug use has been a topic of considerable interest. However, it remains uncertain whether different classes of antihyperglycemic drug therapy are associated with the risk of atrial fibrillation risk. Here, we investigated the association between different classes of antihyperglycemic drugs and new-onset atrial fibrillation (NAF). A case-matched study was performed based on the National Health Insurance Program in Taiwan. Patients who had NAF were considered the NAF group and were matched in a 1:4 ratio with patients without NAF, who were assigned to the non-NAF group. Patients were matched according to sex, age, diabetes mellitus duration, index date, and Charlson Comorbidity Index score. We used multivariate logistic regression controlling for potential confounders to examine the association between different classes of antihyperglycemic drug use and the risk of NAF. Overall, we identified 2,882 cases and 11,528 matched controls for the study. After adjusting for sex, age, comorbidities, and concurrent medications, users of biguanides or thiazolidinediones were at a lower risk of developing NAF when compared with non-users (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71-0.95 and OR 0.72, 95% CI 0.63-0.83, respectively). In contrast, users of insulin were at a higher risk of developing NAF than were non-users (OR 1.19, 95% CI 1.06-1.35). Sulfonylureas, glinides, α-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were not associated with developing the risk of NAF. In conclusion, the use of biguanides or thiazolidinediones may be associated with a low risk of NAF, whereas insulin may be associated with a significant increase in the risk of NAF in patients with type 2 diabetes mellitus during long-term follow-up. Further prospective randomized studies should investigate which specific class of antihyperglycemic drug treatment for diabetes mellitus can prevent or postpone NAF.

Dataset Information

A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case-control study.

Publications

A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case-control study.

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