Efficacy and safety of dabigatran versus warfarin in patients with non-valvular atrial fibrillation

Abstract no. PC023Dabigatran, a direct thrombin inhibitor, is the first new oral anticoagulant approved for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF) as an alternative to warfarin. However, the clinical effectiveness and adverse events concerning the use of dabigatran are not well described outside clinical trial setting. The aim of this study was to compare the efficacy and safety of dabigatran and warfarin in patients with NVAF in the ...postprin

Non-vitamin K oral anticoagulants and risk of fractures: a systematic review and meta-analysis

Aims: Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk. / Methods and results:  PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian–Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75–0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71–0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60–0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74–1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs. / Conclusion: This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture

Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: A population-based cohort study

Background: Whether oral anticoagulation (OAC) can prevent dementia or cognitive impairment (CI) in patients with atrial fibrillation (AF) remains unclear. Objective: The purpose of this study was to investigate the risk of dementia/CI among AF patients with and without OAC treatment. Methods: We conducted a retrospective cohort study using United Kingdom (UK) primary care data (2000–2017). Participants with newly diagnosed AF without a history of dementia/CI were identified. Inverse probability of treatment weights based on propensity scores and Cox regression were used to compare the dementia outcomes. Results: Among 84,521 patients with AF, 35,245 were receiving OAC treatment and 49,276 received no OAC treatment; of these patients, 29,282 were receiving antiplatelets. Over a mean follow-up of 5.9 years, 5295 patients developed dementia/CI. OAC treatment was associated with a lower risk of dementia/CI compared to no OAC treatment (hazard ratio [HR] 0.90; 95% confidence interval 0.85–0.95; P <.001) or antiplatelets (HR 0.84; 95% confidence interval 0.79–0.90; P <.001). No significant difference in dementia risk was observed for direct oral anticoagulants (DOACs) vs warfarin (HR 0.89; 95% confidence interval 0.70–1.14; P = .373), whereas dual therapy (OAC plus an antiplatelet agent) was associated with a higher risk of dementia/CI compared with no treatment (HR 1.17; 95% confidence interval 1.05–1.31; P = .006). Conclusion: OAC use was associated with a lower risk of dementia/CI compared to non-OAC and antiplatelet treatment among AF patients. The evidence for DOAC on cognitive function is insufficient, and further studies including randomized clinical trials are warranted

Association between methylphenidate treatment and risk of seizure: A population-based self-controlled case series study

Background: Individuals with attention-deficit hyperactivity disorder (ADHD) are at increased risk of seizures. Stimulant medications such as methylphenidate are the most commonly prescribed treatment for ADHD, but the association between their therapeutic use and the risk of seizures is unclear. We aimed to investigate the association between methylphenidate treatment and the risk of seizure. Methods: For this population-based observational study, we used the electronic medical record database of the Hong Kong Clinical Data Analysis And Reporting System to identify individuals aged 6–25 years who received at least one methylphenidate prescription during the study period. Individuals with records of seizure or epilepsy before the study period were excluded. Individuals treated with methylphenidate who had seizures during the study period were included in the subsequent analyses, and a self-controlled case-series design was used to control for time-invariant individual characteristics. We did additional analyses using skin infection as a negative control outcome. We compared relative incidence of seizure during periods when individuals were exposed to methylphenidate with that during non-exposed periods. Findings: Of 29 604 individuals prescribed methylphenidate between Jan 1, 2001, and Dec 31, 2017, 269 (199 males and 70 females) had incident seizures. The mean age at baseline was 6·66 years (SD 2·01) and the median age at the incident seizure was 9·69 years (IQR 7·62–12·99). The overall incidence of seizure during methylphenidate treatment was 4·4 per 10 000 patient-years. We detected an increased risk of seizure during the first 30 days of methylphenidate treatment compared with that during non-exposed periods, with an incidence rate ratio of 4·01 (95% CI 2·09–7·68). No increase in risk was identified during the following 31–180 days of treatment (1·13, 0·56–2·25) or during subsequent treatment (1·38, 0·92–2·07). We did not identify an increased risk in any risk window for the negative control outcome analysis. No individuals died because of a seizure during the study period. Interpretation: The incidence of seizures was higher in the period immediately after the start of methylphenidate treatment than in the non-exposed period. No increased risk was observed during continuation of methylphenidate treatment. The association between methylphenidate treatment and seizures immediately after initiation of medication can be seen as a potential safety signal. Monitoring of neurological outcomes in individuals with ADHD is recommended when they first start methylphenidate treatment. Funding: Hong Kong Research Grants Council

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

Background: The effect of sacubitril/valsartan on survival and hospitalization risk in older patients with heart failure has not been explored. We aimed to investigate the risk of hospitalization and mortality with the use of sacubitril/valsartan vs. enalapril in patients with heart failure. / Methods: This was a population-based cohort study using the Hong Kong-wide electronic healthcare database. Patients diagnosed with heart failure and newly prescribed sacubitril/valsartan or enalapril between July 2016 and June 2019 were included. The risk of primary composite outcome of cardiovascular mortality or heart failure-related hospitalization, all-cause hospitalization, heart failure-related hospitalization, cardiovascular mortality and all-cause mortality were compared using Cox regression with inverse probability treatment weighting. Additional analysis was conducted by age stratification. / Results: Of the 44,503 patients who received sacubitril/valsartan or enalapril, 3,237 new users (sacubitril/valsartan, n = 1,056; enalapril, n = 2,181) with a diagnosis of heart failure were identified. Compared with enalapril, sacubitril/valsartan users were associated with a lower risk of primary composite outcome [hazard ratio (HR) 0.58; 95% confidence interval (CI), 0.45–0.75], heart failure-related hospitalization (HR 0.59; 95% CI, 0.45–0.77), all-cause mortality (HR 0.51; 95% CI, 0.36–0.74) and borderline non-significant reductions in all-cause hospitalization (HR 0.85; 95% CI, 0.70–1.04) and cardiovascular mortality (HR 0.63; 95% CI, 0.39–1.02). The treatment effect of sacubitril/valsartan remains unaltered in the patient subgroup age ≥ 65 years (73%). / Conclusions: In real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. The effectiveness remains consistent in the older population

Association between Androgen Deprivation Therapy and Risk of Dementia in Men with Prostate Cancer

The risk of dementia after androgen deprivation therapy (ADT) in patients with advanced prostate cancer (PCa) remains controversial. This study aimed to evaluate the association between ADT and the incidence of dementia in patients with PCa. We identified patients newly diagnosed with PCa in the National Health Insurance Database of Taiwan from 1 January 2002 to 30 June 2016 and in The Health Improvement Network of the United Kingdom (UK) from 1 January 1998 to 31 March 2018. We classified patients with PCa into ADT and ADT-naïve groups. Propensity score (PS) methods were used to minimize the differences in characteristics between the groups. We performed a Cox proportional hazard model to obtain the adjusted hazard ratio (HR) to compare the incidence of dementia between the groups. Our ADT group comprised 8743 and 73,816 patients in Taiwan and the UK, respectively, which were matched 1:1 to ADT-naïve patients by PS. The incidence rates of dementia in the ADT group were 2.74 versus 3.03 per 1000 person-years in the ADT naïve groups in Taiwan, and 2.81 versus 2.79 per 1000 person-years in the UK. There was no statistical difference between ADT and ADT-naïve groups (adjusted HR: 1.12; 95% confidence interval (CI): 0.87–1.43 in Taiwan and adjusted HR: 1.02; 95% CI: 0.85–1.23 in the UK). We found no association between the incidence of dementia and ADT in patients with advanced PCa in either database. Further studies are warranted to evaluate other possible triggers of incident dementia in patients receiving ADT for advanced PCa

Comparative Outcomes Between Direct Oral Anticoagulants, Warfarin, and Antiplatelet Monotherapy Among Chinese Patients With Atrial Fibrillation: A Population-Based Cohort Study

Introduction: Outcomes associated with suboptimal use of antithrombotic treatments (antiplatelets, warfarin, direct oral anticoagulants [DOACs]) are unclear in Chinese patients with atrial fibrillation (AF). Objectives: Our objective was to assess the prescription patterns, quality, effectiveness, and safety of antithrombotic treatments. Methods: This was a population-based cohort study using electronic health records in Hong Kong. Patients newly diagnosed with AF during 2010–2016 were followed up until 2017. Patients at high stroke risk (CHA2DS2-VASc score ≥ 2) and receiving antithrombotic treatments were matched using propensity scoring. We used Cox proportional hazards regression to compare the risks of ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between groups. Results: Of the 52,178 high-risk patients with AF, 27,614 (52.9%) received antithrombotic treatment and were included in the analyses. Between 2010 and 2016, prescribing of antiplatelets and warfarin declined and that of DOACs increased dramatically (from 1 to 32%). Two-thirds of warfarin users experienced poor anticoagulation control. Warfarin and DOACs were associated with lower risks of ischemic stroke (warfarin, hazard ratio [HR] 0.51 [95% confidence interval (CI) 0.36–0.71]; DOACs, HR 0.69 [95% CI 0.51–0.94]) and all-cause mortality (warfarin, HR 0.47 [95% CI 0.39–0.57]; DOACs, HR 0.45 [95% CI 0.37–0.55]) than were antiplatelets. DOACs were associated with a lower risk of ICH than was warfarin (HR 0.53 [95% CI 0.34–0.83]). GIB risks were similar among all groups. Conclusion: Antiplatelet prescribing and suboptimal warfarin management remain common in Chinese patients with AF at high risk of stroke. DOAC use may be associated with a lower risk of ischemic stroke and all-cause mortality when compared with antiplatelets and with a lower risk of ICH when compared with warfarin

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

BACKGROUND: Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. METHODS: Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. RESULTS: Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. CONCLUSION: Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.published_or_final_versio

Impact of the COVID-19 pandemic on use of anti-dementia medications in 34 European and North American countries

INTRODUCTION: The impact of the COVID-19 pandemic on the global use of anti-dementia medication is unknown. We aimed to determine the changes of anti-dementia medication use in Europe (EU) and North America (NA) during the pandemic. METHODS: This is a cross-sectional study using sales data of anti-dementia medications in 2019 and 2020 from 34 EU and NA countries. The monthly uses of anti-dementia medications from January through June in 2020 were compared to the corresponding months in 2019 for each country. RESULTS: In the pre-pandemic period of January to March 2020, 70 out of 102 (3 months x 34 countries) measurements (68.6%) of monthly sales volume showed an increase. In contrast, 76.5% and 85.3% countries showed reduced sales in April and May 2020, respectively. DISCUSSION: These findings indicate changes in use of anti-dementia medications during the pandemic. The delivery of pharmaceutical care for dementia patients may be heavily disrupted in certain countries