Anticoagulant prescribing for atrial fibrillation and risk of incident dementia.
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ABSTRACT: Objective
The aim of this study was to investigate the association between oral anticoagulant type (direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs)) and incident dementia or mild cognitive impairment (MCI) among patients with newly diagnosed atrial fibrillation (AF).Methods
Using linked electronic health record (EHR) data from the Clinical Practice Research Datalink in the UK, we conducted a historical cohort study among first-time oral anticoagulant users with incident non-valvular AF diagnosed from 2012 to 2018. We compared the incidence of (1) clinically coded dementia and (2) MCI between patients prescribed VKAs and DOACs using Cox proportional hazards regression models, with age as the underlying timescale, accounting for calendar time and time on treatment, sociodemographic and lifestyle factors, clinical comorbidities and medications.Results
Of 39 200 first-time oral anticoagulant users (44.6% female, median age 76 years, IQR 68-83), 20 687 (53%) were prescribed a VKA and 18 513 (47%) a DOAC at baseline. Overall, 1258 patients (3.2%) had GP-recorded incident dementia, incidence rate 16.5 per 1000 person-years. DOAC treatment for AF was associated with a 16% reduction in dementia diagnosis compared with VKA treatment in the whole cohort (adjusted HR 0.84, 95% CI: 0.73 to 0.98) and with a 26% reduction in incident MCI (adjusted HR 0.74, 95% CI: 0.65 to 0.84). Findings were similar across various sensitivity analyses.Conclusions
Incident EHR-recorded dementia and MCI were less common among patients prescribed DOACs for new AF compared with those prescribed VKAs.
SUBMITTER: Cadogan SL
PROVIDER: S-EPMC8600601 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Direct oral anticoagulants (DOACs) are indicated for prevention of stroke and embolism in patients with nonvalvular atrial fibrillation (NVAF). These agents have been shown to be non-inferior to warfarin in terms of efficacy and safety. However, their uptake in practice has been variable, and prescribed dosages may be inconsistent with manufacturer recommendations. Objectives:To evaluate patterns of oral anticoagulant use in patients with NVAF, including determination of patient characteristics associated with the prescribing of warfarin or DOACs and whether prescribed dosages of DOACs were concordant with manufacturer recommendations. Methods:This retrospective chart review was conducted from April to September 2017 at Abbotsford Regional Hospital, Abbotsford, British Columbia. Patients at least 18 years of age with NVAF and CHADS-65 score of 1 or higher were included. Patients with contraindications to oral anticoagulants, those with reversible atrial fibrillation, and those undergoing renal dialysis were excluded. The dosage of DOACs was categorized as too low, too high, or correct in relation to manufacturer recommendations for the Canadian product. Results:A total of 120 patients were included. At discharge, 83 (69%) of the patients had a prescription for DOAC, 25 (21%) had a prescription for warfarin, and 12 (10%) had no prescription for an oral anticoagulant. There were no statistically significant differences between the warfarin and DOAC groups with respect to patient characteristics. Among the 56 patients for whom a full DOAC dose was indicated, 7 (13%) received a dose that was too low. Among the 23 patients for whom a full DOAC dose was not indicated, 4 (17%) received a dose that was too high. Conclusions:At the study hospital, most patients with NVAF and CHADS-65 score of at least 1 had a discharge prescription for DOAC. Patient characteristics appeared to be similar between the warfarin and DOAC groups. For a notable proportion of patients who received a DOAC, the dosage was incorrect. Appropriate prescribing of oral anticoagulants could be further improved by education for prescribers and involvement of hospital pharmacists.
| S-EPMC6910852 | biostudies-literature
Project description:Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine-Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person-years) for dementia over a median follow-up of 3.3 (interquartile range, 1.7-5.4) years were 2.79 (95% CI, 2.72-2.85) and 2.04 (95% CI, 1.99-2.08) per 100 person-years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09-1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07-1.15]). Associations were stronger for age <65 (sHR, 1.65 [95% CI, 1.29-2.12]) versus ≥65 (sHR, 1.07 [95% CI, 1.03-1.10]) years (interaction P<0.001); and those without (sHR, 1.20 [95% CI, 1.14-1.26]) versus with chronic kidney disease (sHR, 1.06 [95% CI, 1.01-1.11]; interaction P<0.001). No meaningful differences were seen by sex, race, or ethnicity. Conclusions In a large, diverse community-based cohort, incident AF was associated with a modestly increased risk of dementia that was more prominent in younger patients and those without chronic kidney disease but did not substantially vary across sex, race, or ethnicity. Further studies should delineate mechanisms underpinning these findings, which may inform use of AF therapies.
| S-EPMC10111519 | biostudies-literature
Project description:Background Oral anticoagulants ( OACs ) in patients with atrial fibrillation ( AF ), in addition to reducing stroke risk, could also prevent adverse cognitive outcomes. The purpose of this study was to compare the risk of dementia incidence across patients with AF initiating different OAC s. Methods and Results We identified patients with nonvalvular AF initiating OAC s in 2 US healthcare claim databases, MarketScan (2007-2015) and Optum Clinformatics (2009-2015). Dementia, comorbidities, and use of medications were defined on the basis of inpatient and outpatient claims. We performed head-to-head comparisons of warfarin, dabigatran, rivaroxaban, and apixaban in propensity score-matched cohorts. We calculated hazard ratios ( HR s) and 95% confidence intervals ( CI s) of incident dementia for each propensity score-matched cohort and meta-analyzed database-specific results. We analyzed 307 099 patients with AF from the MarketScan database and 161 346 from the Optum database, of which 6572 and 4391, respectively, had a diagnosis of incident dementia. The mean follow-up of each cohort ranged between 0.7 and 2.2 years. Patients initiating direct OACs experienced lower rates of dementia than those initiating warfarin (dabigatran: HR , 0.85; 95% CI , 0.71-1.01; rivaroxaban: HR , 0.85; 95% CI , 0.76-0.94; apixaban: HR , 0.80; 95% CI , 0.65-0.97). There were no differences in rates of dementia comparing direct OAC user groups (dabigatran versus rivaroxaban: HR , 1.02; 95% CI , 0.79-1.32; dabigatran versus apixaban: HR , 0.92; 95% CI , 0.63-1.36; apixaban versus rivaroxaban: HR , 1.01; 95% CI , 0.86-1.19). Conclusions Patients with AF initiating direct OACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular direct OAC in relation to dementia rates.
| S-EPMC6404188 | biostudies-literature
Project description:It is well-known that atrial fibrillation carries an increased risk of stroke and dementia. The connecting pathogenic common mechanism is the thromboembolic state provided by atrial fibrillation, which is responsible for the acute cerebral events, as well as more saddle anatomic lesions, which accumulating over time, could lead to a progressive cognitive decline. It is plausible, instinctively, that oral anticoagulation could decrease this risk, although the possibility of micro-haemorrhages, which cannot be ignored, could make anticoagulation in this contest even dangerous. In this regard, whether there are firm, well established, evidences documenting a significant reduction in stroke occurrence with anticoagulant treatment in atrial fibrillation, the same level of evidences are not supporting the treatment in preventing dementia. Bringing some more clarity to this issue could have some considerable advantages, also in term of healthcare cost containment, considering the high prevalence of atrial fibrillation and dementia in the elderly.
| S-EPMC7270894 | biostudies-literature
Project description:Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented.To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation.A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ? 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded.Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the combination of ASA, oral anticoagulant, and P2Y12 inhibitor was used for 54% (38/70) of the patients.Fewer than half of the patients in this study received TAT, and almost 20% received non-evidence-based therapy with a direct-acting oral anticoagulant or ticagrelor, alone or in combination. Despite current guideline recommendations, the rate of TAT utilization was lower than rates reported in the literature.
| S-EPMC5008423 | biostudies-other
Project description:OBJECTIVE:Levothyroxine treatment is common among older adults as is atrial fibrillation (AF), yet less is known about its potential effects on the development of dementia. METHODS:The study population included all adults with diagnosed AF (n = 156,104) aged ≥ 45 years in Sweden without an earlier recorded diagnosis of dementia. Individuals with a dispensed prescription of levothyroxine on two or more occasions between July 1 2005 and December 31 2006 in Sweden were considered exposed (n = 12,978; 8.3%), and were compared to all other patients with AF without this treatment. Cox regression with hazard ratios (HRs) and 95% confidence interval (95% CI), with outcome defined as dementia of all causes between January 1, 2007 and December 31, 2015, was used in the analysis. Adjustments were made for socio-demographic factors (age, immigration status, marital status, educational level, neighborhood socioeconomic status), co-morbidity (cardiovascular disease, obesity, diabetes, COPD, depression, anxiety and alcohol related diagnoses), and cardiovascular medications. RESULTS:During follow-up, a total of 9054 patients with AF were diagnosed with dementia (5.8%). We found no significant association of levothyroxine treatment and incident dementia, fully adjusted HR 1.03 (95% CI 0.96-1.11), neither among men and women, nor in different age-groups or subgroups of dementia. CONCLUSION:We found no significant association of levothyroxine treatment and incident dementia among patients with AF, which contrasts some earlier findings.
| S-EPMC6872912 | biostudies-literature
Project description:Background We compared the dementia incidence rate between users and nonusers of oral anticoagulants (OACs) in a large cohort of primary care patients with atrial fibrillation. Methods and Results We performed a retrospective study using an Australia-wide primary care data set, MedicineInsight. Patients aged ≥18 years and newly diagnosed with atrial fibrillation between January 1, 2010, and December 31, 2017, and with no recorded history of dementia or stroke were included and followed until December 31, 2018. We applied a propensity score for 1:1 pair matching of baseline covariates and Cox regression for comparing the dementia incidence rates for OAC users and nonusers. Data were analyzed for 18 813 patients with atrial fibrillation (aged 71.9±12.6 years, 47.1% women); 11 419 had a recorded OAC prescription for at least 80% of their follow-up time. During the mean follow-up time of 3.7±2.0 years, 425 patients (2.3%; 95% CI, 2.1%-2.5%) had a documented diagnosis of dementia. After propensity matching, the incidence of dementia was significantly lower in OAC users (hazard ratio [HR], 0.59; 95% CI, 0.44-0.80; P<0.001) compared with nonusers. Direct-acting oral anticoagulant users had a lower incidence of dementia than non-OAC users (HR, 0.49; 95% CI, 0.33-0.73; P<0.001) or warfarin users (HR, 0.46; 95% CI, 0.28-0.74; P=0.002). No significant difference was seen between warfarin users and non-OAC users (HR, 1.08; 95% CI, 0.70-1.70; P=0.723). Conclusions In patients with atrial fibrillation, direct-acting oral anticoagulant use may result in a lower incidence of dementia compared with treatment with either warfarin or no anticoagulant.
| S-EPMC9075457 | biostudies-literature
Project description:Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.A prolonged QT interval is associated with an increased risk of incident AF.
| S-EPMC3787974 | biostudies-literature
Project description:Psychological stress has been reported as a possible trigger of atrial fibrillation (AF). No studies have investigated whether any association between stress and AF could be modified by genetic susceptibility to AF (AF-genetic risk score (AF-GRS)). 8765 men and 13,543 women from the Malmö Diet Cancer Study, a population-based cohort, were included in the analyses. A variable representing stress was constructed from questions measuring job strain, and from one question assessing non-occupational stress. Cox proportional hazards regression models were adjusted for known covariates of AF. Mean follow-up times and number of recorded incident AF were 14.2 years and 1116 events for men, and 15.1 years and 932 events for women. Among women, high stress was associated with AF in the age adjusted model (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.47) but not following multivariable adjustment (HR, 1.15; 95% CI, 0.95-1.39). Stress was not associated with incident AF in men. AF-GRS was significantly associated with incident AF for both genders. Stress did not interact significantly with genetic susceptibility to AF in men or women. Chronic stress is not associated with long-term incident hospital diagnosed AF. This association does not appear to be modified by genetic susceptibility to AF.
| S-EPMC5307347 | biostudies-literature
Project description:OBJECTIVES:This study sought to identify modifiable risk factors and estimate the impact of risk factor modification on heart failure (HF) risk in women with new-onset atrial fibrillation (AF). BACKGROUND:Incident HF is the most common nonfatal event in patients with AF, although strategies for HF prevention are lacking. METHODS:We assessed 34,736 participants in the Women's Health Study who were free of prevalent cardiovascular disease at baseline. Cox models with time-varying assessment of risk factors after AF diagnosis were used to identify significant modifiable risk factors for incident HF. RESULTS:Over a median follow-up of 20.6 years, 1,495 women developed AF without prevalent HF. In multivariable models, new-onset AF was associated with an increased risk of HF (hazard ratio [HR]: 9.03; 95% confidence interval [CI]: 7.52 to 10.85). Once women with AF developed HF, all-cause (HR: 1.83; 95% CI: 1.37 to 2.45) and cardiovascular mortality (HR: 2.87; 95% CI: 1.70 to 4.85) increased. In time-updated, multivariable models accounting for changes in risk factors after AF diagnosis, systolic blood pressure >120 mm Hg, body mass index ?30 kg/m2, current tobacco use, and diabetes mellitus were each associated with incident HF. The combination of these 4 modifiable risk factors accounted for an estimated 62% (95% CI: 23% to 83%) of the population-attributable risk of HF. Compared with women with 3 or 4 risk factors, those who maintained or achieved optimal risk factor control had a progressive decreased risk of HF (HR for 2 risk factors: 0.60; 95% CI: 0.37 to 0.95; 1 risk factor: 0.40; 95% CI: 0.25 to 0.63; and 0 risk factors: 0.14; 95% CI: 0.07 to 0.29). CONCLUSIONS:In women with new-onset AF, modifiable risk factors including obesity, hypertension, smoking, and diabetes accounted for the majority of the population risk of HF. Optimal levels of modifiable risk factors were associated with decreased HF risk. Prospective assessment of risk factor modification at the time of AF diagnosis may warrant future investigation.
| S-EPMC5873947 | biostudies-literature