Switching of oral anticoagulants in patients with nonvalvular atrial fibrillation: A narrative review.

Approval of direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF) was an important milestone, providing a wider range of treatment options and creating the possibility for drug switching after initiation. In addition to improved utilisation of oral anticoagulants (OACs) for stroke prevention, reports of switching among OACs are growing in the literature; switching may influence clinical outcomes, healthcare costs and patient satisfaction. This review aimed to summarise the current literature on the pattern of OAC switching in patients with AF, including reasons for switching and clinical consequences following switching. A literature search was conducted in PubMed, Scopus and Embase on 27 June 2020. We included 39 articles published after 2013, following the introduction of apixaban. The review found that switching among OACs was common in clinical practice, significantly varying with the type of OAC. Studies reporting the reason for switching and clinical outcomes were comparatively limited. The decision to switch was often related to safety issues (usually bleeding), poor anticoagulation control and ease of use. Patient characteristics, clinical conditions and drug interactions were found to be associated with switching from OACs. Findings regarding bleeding outcomes following switching were inconsistent, possibly confounded by the rationale for switching and the switching protocol. Noting the limited number of studies included and their relatively short follow-up periods, switching did not have a significant impact on the risk of stroke and other thrombotic outcomes. Further prospective studies are needed to understand better potential rationales for switching and the clinical outcomes.

The global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli in the community.

OBJECTIVES: Intestinal colonization by ESBL Escherichia coli and its association with community-acquired MDR infections is of great concern. This review determined the worldwide prevalence of human faecal ESBL E. coli carriage and its trend in the community over the past two decades. METHODS: A systematic literature search was conducted using PubMed, EMBASE and Google Scholar to retrieve articles published between 1 January 2000 and 13 February 2020 that contained data on the prevalence of faecal carriage of ESBL E. coli among healthy individuals. A cumulative (for the whole period) meta-analysis was used to estimate the global and regional pooled prevalence rates. Articles were grouped into study periods of 3 years, and subgroup meta-analyses were undertaken to examine the global pooled prevalence over time. RESULTS: Sixty-two articles covering 29 872 healthy persons were included in this meta-analysis. The cumulative (2003-18) global pooled prevalence of ESBL E. coli intestinal carriage in the community was 16.5% (95% CI 14.3%-18.7%; P  <  0.001). The pooled prevalence showed an upward trend, increasing from 2.6% (95% CI 1.6%-4.0%) in 2003-05 to 21.1% (95% CI 15.8%-27.0%) in 2015-18. Over the whole period, the highest carriage rate was observed in South-East Asia (27%; 95% CI 2.9%-51.3%), while the lowest occurred in Europe (6.0%; 95% CI 4.6%-7.5%). CONCLUSIONS: Globally, an 8-fold increase in the intestinal carriage rate of ESBL E. coli in the community has occurred over the past two decades. Prevention of its spread may require new therapeutic and public health strategies.

Factors influencing oral anticoagulant use in patients newly diagnosed with atrial fibrillation.

BACKGROUND: We investigated factors that influenced oral anticoagulant (OAC) initiation and choice in Australian general practice patients newly diagnosed with AF. METHODS: Using an Australian nationally representative general practice dataset, MedicineInsight, we identified patients newly diagnosed with AF between January 2009 and April 2019. Logistic regression analyses were used to examine factors associated with OAC initiation and choice. RESULTS: A total of 63 212 patients with AF (53.7% males, mean age 72.4 years) were identified. Nearly two-thirds of these patients (40 854 [64.6%]) were initiated on an OAC, at a median time of 6 days after the documented diagnosis date. The proportion of patients who were initiated an OAC increased from 44.8% in 2009 to 72.2% in 2019 (P < .001). High risk of stroke (CHA2 DS2 -VASc, adjusted odds ratio (AOR), 4.39 [95% CI, 3.99-4.83]), low risk of bleeding (ORBIT, AOR, 1.87 [95% CI, 1.72-2.03]), not having a recorded history of dementia (AOR, 1.81 [95% CI, 1.65-1.98]) and male sex (AOR, 1.29 [95% CI, 1.22-1.35]) were independently associated with OAC initiation. Direct-acting oral anticoagulant (DOAC) use increased from 11.9% in 2011 to 94.0% of all OAC initiations in April 2019 (P < .001). CONCLUSIONS: The proportion of newly diagnosed patients with AF initiated on OAC increased markedly following the introduction of the DOACs. Of those initiated, 9 in 10 were receiving a DOAC at the end of the study period. There is potential underuse in women and individuals with dementia.

Stroke risk reassessment and oral anticoagulant initiation in primary care patients with atrial fibrillation: A ten-year follow-up.

AIM: To examine the change in stroke risk over time and determine the proportion of patients with atrial fibrillation (AF) who were initiated on an oral anticoagulant (OAC) as their stroke risk increased from low/moderate to high, using the Australian general practice data set, MedicineInsight. METHODS: A total of 2296 patients diagnosed with AF between 1 January 2007 and 31 December 2008, aged 18 years or older and not initiated on an OAC before 2009, were included. We assessed the change in stroke risk and the proportion of patients who had a recorded prescription of an OAC, each year from 1 January 2009 to 31 December 2018. RESULTS: At baseline, 23.9%, 22.9% and 53.2% were categorised as being at low (score = 0), moderate (score = 1) and high stroke risk (score ≥ 2), respectively, using the sexless CHA2 DS2 -VASc (CHA2 DS2 -VA) score. Overall, the CHA2 DS2 -VA score increased by a mean of 1.34 (95% confidence interval, 1.29-1.39) points over the study period. Nearly two-thirds of patients (65%, 412/632) whose stroke risk changed from baseline low/moderate to high were subsequently prescribed an OAC. The median (interquartile range) lag time from becoming high stroke risk to having OAC initiation was 2 (5) years. CONCLUSIONS: Nearly one-third of patients reclassified as being at high risk of stroke during the study period were not prescribed OAC therapy. Furthermore, the delay in OAC initiation following classification as being at high risk was a median of 2 years, suggesting that more frequent stroke reassessment is needed.

Comparison of renin-angiotensin-aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes.

BACKGROUND: Reports on the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. METHODS: We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). RESULTS: A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. CONCLUSIONS: RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.

Ten-year trends in prescribing of antiarrhythmic drugs in Australian primary care patients with atrial fibrillation.

Despite changes in antiarrhythmic drug (AAD) choice in patients with atrial fibrillation (AF), trends in AAD prescribing remain not investigated. We aimed to examine these changes using a nationwide Australian general practice data from 2009 to 2018. Over the 10 years, AAD prescribing in patients with AF decreased, which was mainly due to a reduction in the use of amiodarone, sotalol and digoxin. In contrast, the use of beta-blockers and flecainide increased.

Quality use of medicines in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) affects drug elimination and patients with CKD require appropriate adjustment of renally cleared medications to ensure safe and effective pharmacotherapy. The main objective of this study was to determine the extent of potentially inappropriate prescribing (PIP; defined as the use of a contraindicated medication or inappropriately high dose according to the kidney function) of renally-cleared medications commonly prescribed in Australian primary care, based on two measures of kidney function. A secondary aim was to assess agreement between the two measures. METHODS: Retrospective analysis of routinely collected de-identified Australian general practice patient data (NPS MedicineWise MedicineInsight from January 1, 2013, to June 1, 2016; collected from 329 general practices). All adults (aged ≥18 years) with CKD presenting to general practices across Australia were included in the analysis. Patients were considered to have CKD if they had two or more estimated glomerular filtration rate (eGFR) recorded values < 60 mL/min/1.73m2, and/or two urinary albumin/creatinine ratios ≥3.5 mg/mmol in females (≥2.5 mg/mmol in males) at least 90 days apart. PIP was assessed for 49 commonly prescribed medications using the Cockcroft-Gault (CG) equation/eGFR as per the instructions in the Australian Medicines Handbook. RESULTS: A total of 48,731 patients met the Kidney Health Australia (KHA) definition for CKD and had prescriptions recorded within 90 days of measuring serum creatinine (SCr)/estimated glomerular filtration rate (eGFR). Overall, 28,729 patients were prescribed one or more of the 49 medications of interest. Approximately 35% (n = 9926) of these patients had at least one PIP based on either the Cockcroft-Gault (CG) equation or eGFR (CKD-EPI; CKD-Epidemiology Collaboration Equation). There was good agreement between CG and eGFR while determining the appropriateness of medications, with approximately 97% of the medications classified as appropriate by eGFR also being considered appropriate by the CG equation. CONCLUSION: This study highlights that PIP commonly occurs in primary care patients with CKD and the need for further research to understand why and how this can be minimised. The findings also show that the eGFR provides clinicians a potential alternative to the CG formula when estimating kidney function to guide drug appropriateness and dosing.

Factors associated with first-line antiretroviral treatment failure in adult HIV-positive patients: a case-control study from Ethiopia.

BACKGROUND: Treatment failure has become a significant challenge in patients taking antiretroviral therapy (ART). The aim of the present study was to identify risk factors for first-line ART failure among patients attending clinical follow-up. METHODS: A 1:2 matched case-control study (by age, sex, and treatment duration since initiated on ART) was conducted from June 2015 to July 2017 on adult patients (aged ≥15 years) who were on ART for at least 6 months. Cases were selected from patients who were switched to second-line ART after first-line ART failure (viral load ≥1000 copies/mL). Controls were randomly selected from patients on first-line ART with viral load < 50 copies/mL. Data were collected using an interview questionnaire, reviewing chart and electronic health records and laboratory tests. Multivariate logistic regression analysis was performed to identify risk factors for treatment failure. RESULTS: Of the 273 patients who participated in this study, 55% were males. Ninety-one cases were compared with 182 controls. The median age of participants was 40 years and the median duration of treatment since initiated on ART was 69 months. Independent risk factors associated with first-line antiretroviral treatment failure were discontinuation of ART (adjusted odds ratio (AOR) = 9.8, 95% confidence interval (CI): 4.0-23.8), baseline CD4 lymphocyte count ≤50 cells/mm3 (AOR = 3.8, 95% CI: 1.5-9.6) and persistent diarrhea (AOR = 4.4, 95% CI: 1.5-13.2). The risk of ART failure was high and comparable whether the duration of ART discontinuation was greater or less than 1 month (crude odds ratio (COR) = 6.3 and 8. 5 respectively, p-value < 0.001). Frequent eating of a diet containing wheat or barley (AOR = 2.3, 95% CI: 0.9-5.4) showed a trend to be a risk factor for first-line ART failure (p-value = 0.064). CONCLUSIONS: Our findings underscore the importance of avoiding ART discontinuation of any duration, early initiation of ART and diarrhea management to prevent first-line ART failure.

Antiretroviral adherence and treatment outcomes among adult Ethiopian patients.

Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy (ART) in sub-Saharan Africa is a major challenge. The objective of this study was to determine patient, regimen, disease, patient-provider, and healthcare-related factors associated with adherence with ART over a one-year period, and assess the impact of adherence on treatment outcomes. We performed a prospective, observational study among 246 patients who were initiated on ART in Ethiopia. Of 172 who completed follow-up, 130 (75.6%) had ≥95% adherence. In the multivariate analyses, a higher baseline BMI (OR, 1.2; 95% CI 1.0, 1.4) and use of reminder devices (OR, 9.1; 95% CI 2.0, 41.6) remained positively associated with adherence, while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/µL [interquartile range (IQR), 72-324 cells/µL] vs. 132 cells/µL [IQR, 43-190 cells/µL]; p = 0.026). Our findings indicate that interventions aimed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices, and monitor HIV symptoms and adverse reaction distress and nutritional status.

The effect of pharmacist-led interventions on the appropriateness and clinical outcomes of anticoagulant therapy: a systematic review and meta-analysis.

AIM: Although pharmacist-led interventions in anticoagulant (AC) therapy are widely accepted, there is a lack of evidence comparing their effectiveness with usual care in terms of AC therapy appropriateness and clinical outcomes. We aimed to estimate the comparative effectiveness of pharmacist-led interventions on the appropriateness and clinical outcomes of AC therapy. METHODS AND RESULTS: Adhering to the PRISMA guidelines, we searched PubMed, EMBASE, and Scopus databases to identify randomized controlled trials and quasi-experimental and cohort studies published between 2010 and 2023. A random-effects model was used to calculate pooled intervention effects. We assessed heterogeneity (using Higgins' I2 and Cochran's Q) and publication bias (using Egger's test, the trim-and-fill method, and visualization of the funnel plot). In total, 35 studies involving 10 374 patients in the intervention groups and 11 840 in the control groups were included. The pharmacist-led interventions significantly improved the appropriateness of AC therapy [odds ratio (OR): 3.43, 95% confidence interval (CI): 2.33-5.06, P < 0.01]. They significantly decreased total bleeding [relative risk (RR): 0.75, 95% CI: 0.58-0.96, P = 0.03) and hospitalization or readmission (RR: 0.64, 95% CI: 0.41-0.99, P = 0.04). However, the impact of the pharmacist-led interventions on thromboembolic events (RR: 0.69, 95% CI: 0.46-1.02, P = 0.07) and mortality (RR: 0.76, 95% CI: 0.51-1.13, P = 0.17) was not significant. CONCLUSION: Pharmacist-led interventions demonstrated superior outcomes in optimizing AC therapy compared with usual care. Further research is needed to evaluate pharmacist-led interventions' cost-effectiveness and long-term sustainability. PROSPERO registration number: CRD42023487362.

Clinical outcomes of oral anticoagulant discontinuation in atrial fibrillation: a systematic review and meta-analysis.

INTRODUCTION: Oral anticoagulants (OACs) should generally be continued lifelong in patients with atrial fibrillation (AF) to ensure optimal benefits, unless contraindications arise. However, discontinuation of OACs might occur for various reasons, potentially affecting clinical outcomes. In this review, we synthesized evidence on the clinical outcomes following OAC discontinuation in patients with AF. METHODS: We conducted a systematic review and meta-analysis using PubMed, Embase and Scopus. Cohort or case-control studies were included if data were available on clinical outcomes of OAC discontinuation, compared with continuation, in patients with AF. A random-effect meta-analyses were conducted for key outcomes of stroke, mortality, and major bleeding. RESULTS: Eighteen observational studies having a total of 283,418 patients were included. Discontinuation significantly increased the risk of stroke (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.58-2.23), all-cause (HR 1.90; 95% CI 1.40-2.59) and cardiovascular (HR 1.83; 95% CI 1.06-3.18) mortality. The risk of major bleeding was not significantly different between the discontinued and continued groups (HR 1.04; 95% CI 0.72-1.52). CONCLUSIONS: Discontinuation of OAC therapy was associated with an increased risk of stroke and mortality, with no difference in the risk of major bleeding. Acknowledging heterogeneity among the studies, the findings underline the need to ensure continuity of OAC therapy in patients with AF to prevent thrombotic complications and associated mortality. PROSPERO REGISTRATION NUMBER: CRD42020186116.

Hypocalcemic tetany associated with simultaneous administration of cimetidine and nifedipine: a case report.

BACKGROUND: Acute hypocalcemia is generally caused by a sudden drop in serum calcium ion and presents with a mild or severe form of tetany. Even though the occurrence of hypocalcemia is well documented with certain drugs such as calcium chelators, bisphosphonates, and cisplatin, it is a very unusual and poorly documented adverse event with cimetidine and nifedipine. Here, we present a case of severe hypocalcemic tetany during simultaneous administration of cimetidine and nifedipine in a hypertensive patient with dyspepsia. CASE PRESENTATION: A 46-year-old known human immunodeficiency virus patient from Ethiopia on antiretroviral therapy over the past 14 years presented to the emergency department with acute exacerbation of dyspepsia and hypertensive urgency. She was given intravenous cimetidine (400 mg) and oral nifedipine (30 mg) simultaneously. One hour after the administration of these two drugs, she developed severe hypocalcemic tetany with carpopedal spasm, involuntary plantar flexion, and muscle spasms. She also had severe retrosternal chest pain and shortness of breath. Her blood pressure was 160/110 mmHg during the attack and she had no skin changes, such as urticaria. She was immediately given 1 g of calcium gluconate intravenously over 30 minutes. The carpopedal spasm progressively decreased during calcium gluconate administration. An hour later, she completely regained voluntary movement of her fingers and feet. The chest pain persisted, but resolved over the next 12 hours. The patient was discharged home after 2 days of observation. This is an unusual adverse effect that needs caution during concomitant administration of these drugs. CONCLUSIONS: Severe hypocalcemic tetany can occur with concomitant administration of cimetidine and nifedipine. Immediate treatment with calcium gluconate quickly reverses this adverse event. Concomitant administration of these drugs should be done with caution or be avoided if possible.

Oral Anticoagulant Use in Patients with Atrial Fibrillation at Low Risk of Stroke and Associated Bleeding Complications.

BACKGROUND: The use of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) and low stroke risk might cause more harm than benefit. Little attention has been given to address its prevalence and associated consequences. This study aimed to investigate the prescription rate of OACs, identify associated factors, and describe incident bleeding events in low-risk patients. METHODS: We included patients with a new diagnosis of AF between 1 January 2011 and 31 December 2018 having a low risk of stroke (CHA2DS2-VASc score of 0 for males and 1 for females) from Australian general practice data (MedicineInsight). Patients were classified as OAC users if there was a recorded prescription of an OAC within 60 days of AF diagnosis, and factors associated with the prescription of an OAC were assessed using logistic regression. Recorded incident bleeding events were identified within 6 months after AF diagnosis or after OAC initiation for OAC non-users and users, respectively. The risk of bleeding was compared between the two groups by adjusting their baseline differences using propensity score matching. RESULTS: The study included 2810 low-risk patients (62.3% male) with a mean age of 49.3 ± 10.8 years. Of the total, 705 (25.1%) patients had a record of OAC prescription within 60 days of diagnosis of AF. Older age (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.03-1.04) and diagnosis periods (2015-2016 [OR 1.46; 95% CI 1.10-1.94] and 2017-2018 [OR 1.65; 95% CI 1.17-2.23] vs. 2011-2012) were associated with higher odds of OAC initiation. Female sex (OR 0.71; 95% CI 0.59-0.85), higher bleeding risk (ORBIT score; OR 0.80; 95% CI 0.68-0.94), and higher socioeconomic index for areas (SEIFA) quintiles (SEIFA quintiles; 2 [OR 0.65; 95% CI 0.48-0.88], 3 [OR 0.74; 95% CI 0.56-0.98], 4 [OR 0.70; 95% CI 0.52-0.94], 5 [OR 0.69; 95% CI 0.52-0.91] compared with quintile 1) were associated with lower odds of OAC prescription. A total of 52 (in 1.8% of patients) incident bleeds were identified, with 18 (2.6%) among OAC users. The rate of bleeding was not significantly different between users and non-users after matching. However, within OAC users, commencement of OAC was associated with an increased risk of bleeding compared to the period before OAC initiation (p = 0.006). CONCLUSIONS: One in four patients at low risk of stroke received an OAC within 60 days of AF diagnosis. Older age and the period following the widespread availability of direct-acting OACs were associated with an increased likelihood of OAC prescription. Positively, using OACs was not associated with an increased rate of bleeding compared to non-users.

Ten-Year Trends in Psychotropic Prescribing and Polypharmacy in Australian General Practice Patients with and without Dementia.

OBJECTIVE: Little research has evaluated trends in psychotropic prescribing and polypharmacy in primary care patients, especially those with dementia. We sought to examine this in Australia from 2011 to 2020 using the primary care dataset, MedicineInsight. METHODS: Ten consecutive serial cross-sectional analyses were performed to evaluate the proportion of patients aged 65 years or more, with a recorded diagnosis of dementia, who were prescribed psychotropic medications within the first six months of each year from 2011 to 2020. This proportion was compared with propensity score-matched control patients without dementia. RESULTS: Before matching, 24,701 patients (59.2% females) with, and 72,105 patients (59.2% females) without, a recorded diagnosis of dementia were included. In 2011, 42% (95% confidence interval [CI] 40.5-43.5%) of patients in the dementia group had at least one recorded prescription of a psychotropic medication, which declined to 34.2% (95% CI 33.3-35.1%; p for trend < 0.001) by 2020. However, it remained unchanged for matched controls (36% [95% CI 34.6-37.5%] in 2011 and 36.7% [95% CI 35.7-37.6%] in 2020). The greatest decline in the dementia groups by medication class was for antipsychotics (from 15.9% [95% CI 14.8-17.0%] to 8.8% [95% CI 8.2-9.4%]; p for trend < 0.001). During this period, the prevalence of psychotropic polypharmacy (use of two or more individual psychotropics) also decreased from 21.7% (95% CI 20.5-22.9%) to 18.1% (95% CI 17.4-18.9%) in the dementia groups, and slightly increased from 15.2% (95% CI 14.1-16.3%) to 16.6% (95% CI 15.9-17.3%) in the matched controls. CONCLUSIONS: The decline in psychotropic prescribing, particularly antipsychotics, in Australian primary care patients with dementia is encouraging. However, psychotropic polypharmacy still occurred in almost one in five patients with dementia at the end of the study period. Programs focused on encouraging further reductions in the use of multiple psychotropic drugs in patients with dementia are recommended, particularly in rural and remote regions.

Oral Anticoagulant Discontinuation and Its Predictors in Patients with Atrial Fibrillation.

BACKGROUND: Oral anticoagulants (OACs) are important in reducing the risk of ischaemic stroke in people with atrial fibrillation (AF). Although patients need to take their OAC continuously, it has been suggested that discontinuation is common in clinical practice, and this could predispose patients to thrombotic complications. AIMS: To investigate the rate of OAC discontinuation and its predictors in patients with AF, using national data from Australian general practices. METHODS: We analysed data obtained from NPS MedicineWise's MedicineInsight dataset. We included patients with a recorded diagnosis of AF who newly started an OAC between 1 January 2013 and 31 December 2017. Patients were considered persistent if an OAC was prescribed continuously without discontinuing more than 60 days gap in therapy. The follow-up period was 12 months post-initiation. Multivariable models were used for the analysis of predictors. RESULTS: Of 16,075 patients included in the cohort, 47.3% were females, and the mean age was 74.6 (SD 10.2) years. The overall OAC discontinuation rate was 13.2% (confidence interval (CI) 12.6-13.7%) by 12 months post-initiation. The discontinuation rates for warfarin, apixaban, dabigatran and rivaroxaban were 18.3% (95% CI 17.2-19.5%), 10.1% (95% CI 9.2-11.0%), 10.9% (95% CI 9.4-12.5%) and 12.2% (95% CI 11.4-13.2%), respectively. Warfarin had a significantly higher risk of discontinuation compared to direct-acting OACs. Factors that are known to increase the risk of stroke (older age, diabetes, and hypertension) were associated with better persistence. CONCLUSIONS: A relatively high proportion of patients with AF continued OAC therapy by 12 months post-initiation. Positively, patients with the highest risk of stroke and lowest risk of bleeds seemed to have better persistence.

Improving Knowledge and Early Detection of Atrial Fibrillation through a Community-Based Opportunistic Screening Program: What's Your Beat?

A community-based opportunistic screening program was implemented to (i) improve atrial fibrillation (AF) awareness and detection and (ii) assess the performance of the Microlife WatchBP Home A for detecting AF when used in community screening. Screening sessions were conducted among people aged ≥ 65 years with no history of AF at public events across Tasmania, Australia. Participants with positive screening results were referred to their general medical practitioner for assessment. The device's performance was assessed using the positive predictive value. A total of 1704 eligible participants were screened at 79 sessions. Of these people, 50 (2.9%) had a positive screening result. The device correctly identified AF in 22 (46.8%) participants with positive results. Among those with subsequently confirmed AF, 6 (27.3%) had a history of AF but were not aware of the diagnosis, and 16 (72.7%) were identified to have previously undiagnosed AF, with an overall prevalence of 0.9% (95% CI, 0.58 to 1.52). Oral anticoagulation therapy was initiated in 12 (87.5%) eligible participants. The positive predictive value of the device was 46.8% (95% CI, 33.3 to 60.7). Given the relatively low performance of the device, its application in community-based opportunistic screening programs for AF is unlikely to be cost-effective.

Incidence of Osteoporosis in Primary Care Patients with Atrial Fibrillation Receiving Different Oral Anticoagulants.

Background: Studies investigating the association between the use of oral anticoagulants (OACs) and osteoporosis are limited. We aimed to determine the risk of osteoporosis in patients with atrial fibrillation (AF) and receiving different OACs. Methods: We performed a population-based cohort study using a nationwide primary care dataset, MedicineInsight. Patients aged between 18 and 111 years with AF and newly recorded OAC prescriptions between 1 January 2013 and 31 December 2017 were included and followed until 31 December 2018. We applied propensity score matching to control for patients' baseline characteristic differences before calculating adjusted hazard ratios (aHRs) for a new diagnosis of osteoporosis, using Cox proportional hazard models. Results: A total of 18,454 patients (1714 prescribed dabigatran, 5871 rivaroxaban, 5248 apixaban and 5621 warfarin) were included. Of these, 39.5% were females, and the overall mean age (standard deviation [SD] was 73.2(10.3) years. Over a mean follow-up of 841 days, 1627 patients (1028 receiving direct-acting oral anticoagulants (DOACs) and 599 warfarin) had a newly recorded diagnosis of osteoporosis. The weighted incidence rates (95% confidence interval; CI) per 100 person-years of treatment were 5.0 (4.7−5.2) for warfarin, 4.3 (3.8−4.8) for dabigatran, 3.6 (3.3−3.8) for rivaroxaban, and 4.4 (4.0−4.7) for apixaban. Overall, DOAC use was associated with a significantly lower risk of a new diagnosis of osteoporosis than warfarin use (aHR, 0.79, 95% confidence interval (CI) 0.74−0.85; p < 0.001). Use of each individual DOAC was associated with a significantly lower risk of osteoporosis compared with warfarin (aHRs, 0.75, 95% CI 0.69−0.82 for rivaroxaban; 0.78, 95% CI 0.71−0.86 for apixaban; 0.88, 95% CI 0.77−0.99 for dabigatran). Conclusion: Compared with warfarin, the use of DOACs was associated with a significantly lower risk of developing osteoporosis in patients with AF. This association remained significant when individual DOACs were compared with warfarin.

Switching of oral anticoagulants in atrial fibrillation: a cohort study using Australian general practice data.

BACKGROUND: We assessed switching patterns of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) in the period following widespread availability of the direct-acting oral anticoagulants (DOACs). RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted using NPS MedicineWise's MedicineInsight dataset, collected from Australian general practices. Patients with AF who newly commenced an OAC between 1 January 2013 and 30 September 2017 were included. The switching rate was calculated within 12 months post-initiation. Switching rates between OACs were compared, and predictors of switching were identified. RESULTS: We included 15,020 patients who were recorded as having been commenced on warfarin or a DOAC. Overall, 5.7% of patients switched their OAC within 12 months. The switching rates from warfarin, apixaban, dabigatran and rivaroxaban were 9.4%, 2.6%, 8.9% and 4.0%, respectively. Compared to apixaban, commencement on warfarin, dabigatran or rivaroxaban was associated with a higher risk of switching to another OAC. Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min were more likely to switch from DOACs to warfarin and less likely to switch from warfarin, compared to those with an eGFR >60 mL/min. CONCLUSION: There was a low switching rate between OACs in Australian general practice patients with AF. A key determinant of switching appeared to be kidney disease.

Eight-Year Trends in Direct-Acting Oral Anticoagulant Dosing, Based on Age and Kidney Function, in Patients With Atrial Fibrillation.

OBJECTIVE: Concerns have been raised over the appropriateness of dosing of direct-acting oral anticoagulants (DOACs) in clinical practice. We investigated this issue in patients who were initiated on a DOAC in Australian general practices. METHODS: This was a retrospective study among patients newly diagnosed with atrial fibrillation (AF) who were prescribed DOACs, using data obtained from 417 general practice sites across Australia over 8 years (2011-2019). Direct-acting oral anticoagulant dosing was compared with published recommendations, in relation to age and kidney function. RESULTS: A total of 11,251 patients (mean age, 72.8 y; 46.8% female) newly diagnosed with AF were prescribed a DOAC. Of these, 2667 patients (23.7%) had a recorded prescription of a potentially inappropriate DOAC dosage, of whom 2304 (86.4%) and 283 (10.6%) were prescribed lower and higher than the recommended dosage, respectively. The remaining 80 patients (3.0%) were initiated on DOACs when contraindicated based on renal function. Overall, the proportion of patients who seemed to be initiated on a potentially inappropriate DOAC dose decreased from 38.3% (95% confidence interval, 26.1%-51.8%) in 2012 to 22.7% (95% confidence interval, 19.8%-26.0%; P < 0.001) in 2019. By 2019, 19.4%, 20.3%, and 9.3% of the patients with a recorded prescription of apixaban, rivaroxaban, and dabigatran, respectively, received a lower-than-guideline-recommended dose. The patients were more likely to be prescribed a potentially inappropriate dosage if they were elderly with multiple comorbidities. CONCLUSIONS: Potential inappropriate DOAC dosing is a problem in the prevention of stroke associated with AF. Nearly 1 in 5 patients received a lower-than-guideline-recommended dose, indicating a need for strategies to raise awareness among prescribers.

Risk of osteoporosis in patients with atrial fibrillation with and without oral anticoagulant therapy.

BACKGROUND: We aimed to compare the risk of developing osteoporosis in patients prescribed warfarin or direct-acting oral anticoagulants (DOACs) with those with no therapy. RESEARCH DESIGN AND METHODS: We included 37,632 patients aged between 18 and 111 years with a recorded diagnosis of AF between 1 January 2013 and 31 December 2017. Patients were followed until the diagnosis of osteoporosis, switch or discontinuation of the OAC, last clinical visit, or end of the study period, whichever occurred first. The incidences of new-onset osteoporosis were calculated using the Cox proportional hazards model. RESULTS: Of total, 16,995 (45.2%) had no recorded OAC prescription, and 20,637 had a recorded prescription of warfarin (6,609) or DOAC (14,028). Compared with those not prescribed an OAC, the risk of being diagnosed with new-onset osteoporosis increased in patients prescribed warfarin (HR 2.22, 95% CI 2.00-2.47, p < 0.001) and DOACs (HR 1.42, 95% CI 1.29-1.58, p < 0.001). However, the effect of DOACs was not statistically significant (HR 1.07, 95% CI 0.86-1.33, p < 0.535) after excluding patients with at least one recorded prescription of systemic corticosteroids, antiepileptics, or proton pump inhibitors. CONCLUSIONS: Use of warfarin or DOACs was associated with a significantly increased risk of developing osteoporosis compared with no OAC treatment.