Cost-Effectiveness of Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation in Hong Kong

Objectives: The emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke related to nonvalvular atrial fibrillation (NVAF). Several DOACs are available on the market, while the cost-effectiveness comparison among DOACs and vitamin K antagonist (warfarin) in NVAF management in Hong Kong market remains scarce. The objective of this study was to assess the cost-effectiveness of DOACs and warfarin from a Hong Kong public institutional perspective to inform formulary listing decisions. / Methods: A previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1000 patients. Net monetary costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran (110 mg or 150 mg twice daily), and rivaroxaban (20 mg once daily). Probabilistic sensitivity analyses were conducted to address study uncertainties. / Results: In base-case results, all DOACs were associated with greater QALYs improvements and lower costs than warfarin. Rivaroxaban, apixaban, dabigatran 150 mg, dabigatran 110 mg, and warfarin resulted in net costs US dollar (USD) 8088, USD 8240, USD 8566, USD 8653, and USD 16 363 and net QALY 5.87, 6.017, 6.022, 5.98, and 5.829, respectively. In probabilistic sensitivity analysis, the probabilities of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost-effective of 2000 iterations were 0%, 0%, 29.4%, 33.2%, and 37.4%, respectively. / Conclusion: Apixaban was the most cost-effective option compared with other DOACs and warfarin in the management of NVAF; this conclusion is consistent under all the tested uncertainty scenarios

Polypharmacy and Antidepressant Acceptability in Comorbid Depression and Type 2 Diabetes

BACKGROUND: Polypharmacy may increase the risk of drug interactions, side-effects and poor adherence. However, the impact of polypharmacy on antidepressant acceptability in individuals with type 2 diabetes (T2DM) is unknown. AIM: In adults with T2DM, to investigate the association between the number of prescribed medications and: i) early antidepressant discontinuation (<32 weeks); ii) switching antidepressant agents. DESIGN: Cohort study using UK primary care data from the years 2000-2018. METHODS: We used cox regression with penalised B-splines to describe the association between the number of concurrently prescribed medications at the time of starting antidepressant treatment, and each of our outcomes. RESULTS: We identified 73,808 individuals with comorbid depression and T2DM starting antidepressant treatment for the first time. The median number of concurrent medications prescribed was 7. Within 32 weeks, 44.26% of participants discontinued antidepressant treatment altogether, and 11.75% of participants switched antidepressant agents. We found an inverse relationship between the number of concurrent medications and discontinuing antidepressant treatment altogether. The median number of 7 concurrent medications was associated with a 65.06% decrease early antidepressant discontinuation HR 0.45, 95% CIs 0.37-0.55). We found no evidence of an association, in our main analysis, between the number of concurrent medications and switching antidepressant agents. CONCLUSIONS: Early discontinuation of antidepressants is common in adults with T2DM. However, individuals with higher levels of concurrent polypharmacy may be more adherent to treatment. These are likely to represent individuals with worse physical/mental health. Individuals with lower levels of concurrent polypharmacy may benefit from adherence support

Association between polypharmacy and depression relapse in individuals with comorbid depression and type 2 diabetes: a UK electronic health record study

BACKGROUND: Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the 'high risk of relapse' group for whom longer antidepressant treatment durations are recommended. AIMS: In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment. METHOD: This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures. RESULTS: We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32-3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased - individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25-2.48). We found no interaction between polypharmacy and previous antidepressant duration. CONCLUSIONS: Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment

Trends in the incidence of dementia in people with hypertension in the UK 2000 to 2021

INTRODUCTION: We investigated trends in the incidence of dementia in UK adults with hypertension. METHODS: Primary care electronic health records from IQVIA Medical Research Data UK, previously known as THIN, were used to identify 2,133,118 adults aged ≥40 years with hypertension over 2000 to 2021. The annual incidence rate and average annual percentage change in recorded dementia diagnoses were estimated and stratified by sex, 10-year age bands, Townsend deprivation quintiles and dementia subtype. RESULTS: The crude incidence rate of dementia in people with hypertension increased from 1.98 (95% confidence internal [CI] 1.89-2.07) per 1000 person-years at risk (PYAR) in 2000 to 5.29 per 1000 PYAR (95% CI 5.07-5.53) in 2021, corresponding to an average annual increase of 4.1% (95% CI 3.3-5.0). Those aged ≥80 years, the most economically deprived (Townsend = 5), and Alzheimer's disease subtype reported the highest incidence rate within their respective categories. DISCUSSION: The annual incidence rate of dementia in the hypertensive population has increased over the last 22 years. HIGHLIGHTS: New dementia diagnosis in the hypertensive population has increased over 22 years.The Alzheimer's disease subtype reported the highest incidence rate in people with hypertension.Difference in dementia incidence between hypertensive females and males has reduced.Difference in dementia incidence among deprivation categories has reduced in recent years

Association between oral fluoroquinolones and seizures: A self-controlled case series study.

OBJECTIVES: The aim of this study was to investigate the association and to estimate the crude absolute risk of seizure among patients exposed to fluoroquinolones (FQs) in Hong Kong and the United Kingdom. METHODS: A self-controlled case series study was conducted. Data were collected from the Hong Kong Clinical Data Analysis and Reporting System database and the Clinical Practice Research Datalink. Patients who were prescribed any oral FQ and had an incident seizure diagnosis from 2001 to 2013 were included. The risk windows were defined as pre-FQ start, FQ-exposed, and post-FQ completion. Incidence rate ratios were estimated in all risk windows and compared with baseline periods. A post hoc subgroup analysis was conducted to examine the effect of patients with a history of seizure. RESULTS: An increased incidence rate ratio was found in the pre-FQ start periods and no association was found in the post-FQ completion periods in both databases. The crude absolute risk of an incident seizure in 10,000 oral FQ prescriptions was 0.72 (95% confidence interval 0.47-1.10) in the Clinical Data Analysis and Reporting System and 0.40 (95% confidence interval 0.30-0.54) in the Clinical Practice Research Datalink. The rate ratio during treatment was not higher than pre-FQ start periods among patients with a history of seizure, therefore the results did not raise serious concerns. CONCLUSIONS: This study does not support a causal association between the use of oral FQs and the subsequent occurrence of seizure. An increased risk before the FQ exposure period suggests that the clinical indication for which FQ was prescribed may have contributed to the development of seizure rather than the drug itself

Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis.

INTRODUCTION: It was postulated that antibiotics including macrolides could be used for the secondary prevention of coronary heart disease but recent studies showed that macrolides increase the cardiovascular risk. We aimed to review the evidence of cardiovascular risk associated with macrolides regarding duration of effect and risk factors; and to explore the potential effect of statins for the prevention of cardiovascular events as a result of macrolide use. METHODS: Several electronic databases (PubMed, EMBASE, Cochrane library) were searched to identify eligible studies. Observational studies and randomized controlled trials that investigated the association between macrolides and cardiovascular events in adults aged ≥18 years were included. A meta-analysis was conducted to investigate the short- and long-term risks of cardiovascular mortality, myocardial infarction, arrhythmia, and stroke. Methodological quality was assessed by the Newcastle-Ottawa scale and the Cochrane Collaboration's tool. The body of evidence was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines. RESULTS: Observational studies were found to have a short-term risk of cardiovascular outcomes including cardiovascular mortality, myocardial infarction, and arrhythmia associated with macrolides but no risk was found in randomized controlled trials. However, no association for long-term risk (ranging from >30 days to >3 years) was observed in observational studies or randomized controlled trials. LIMITATIONS: The included studies reported different units of denominators for absolute risk and used different outcome definitions, which might increase the heterogeneity. CONCLUSIONS: More studies are required to investigate the short-term cardiovascular outcomes associated with different types of macrolides. Future studies are warranted to evaluate the effect of statins for preventing excess acute cardiovascular events associated with clarithromycin or other macrolides

Concurrent Use of Oral Anticoagulants and Sulfonylureas in Individuals With Type 2 Diabetes and Risk of Hypoglycemia: A UK Population-Based Cohort Study

OBJECTIVE: To investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression. RESULTS: 109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10–1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27–1.10) when compared with sulfonylureas only. CONCLUSIONS: We provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications

Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

Background: Studies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression. Methods: Individuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin–norepinephrine reuptake inhibitors [SNRIs], and others). Findings: A total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]). Interpretation: Within-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians’ benefit-risk assessments when prescribing antidepressants

Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series.

BACKGROUND: Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction (MI) and proton pump inhibitors (PPIs) using a self-controlled case series (SCCS) with an active comparator. METHODS: We conducted a SCCS using a population-wide database from Hong Kong from 2003-2014. Adult with ≥1 outpatient oral PPI prescription or H2 receptor antagonist (H2RA) and MI during the observation period were included. We used both simple ratio and effect modifier approaches to SCCS with active comparators to obtain comparator adjusted estimates. RESULTS: A total of 2802 and 1889 people with MI who had exposure to PPIs and H2RA were included respectively. We observed a higher risk of MI during days 1-14 following the start of PPI prescription (Incidence rate ratio (IRR): 2.30, 95% confidence interval (CI): 1.76-3.00) versus baseline. Similarly, we observed a higher risk of MI during days 1-14 following the start of H2RA prescription (IRR: 2.46, 95%CI: 1.92-3.16) versus baseline. In the novel SCCS analyses, comparator adjusted estimates were 0.93 (95%CI: 0.57-1.30) and 0.83 (95%CI: 0.58-1.20) during days 1-14 in simple ratio and effect modifier approach, respectively. CONCLUSIONS: We observed no difference in risk of MI associated with PPIs compared with baseline using H2RA as the active comparator. The elevated risk of MI associated with PPIs is likely due to protopathic bias. More studies are required to explore the feasibility of using active comparators in SCCS to address protopathic bias in addition to confounding