Utilization and long‐term persistence of direct oral anticoagulants among patients with nonvalvular atrial fibrillation and liver disease

Aims: We characterized the utilization and long-term treatment persistence of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF) and liver disease. Method: Using the UK Clinical Practice Research Datalink, we assembled a population-based cohort of NVAF patients with liver disease initiating oral anticoagulants between 2011 and 2020. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) of the association between patient characteristics and initiation of DOACs vs vitamin K antagonists (VKAs). Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of the association between patient characteristics and the switch from VKAs to DOACs vs remaining on VKAs. We also assessed the 5-year treatment persistence with DOACs vs VKAs, and whether ischemic stroke or bleeding preceded treatment discontinuation. Results: Our cohort included 3167 NVAF patients with liver disease initiating DOACs (n = 2247, 71%) or VKAs (n = 920, 29%). Initiators of DOACs were more likely to have prior ischemic stroke (OR 1.44, 95% CI 1.12-1.85) than VKA initiators but less likely to have used antiplatelet agents (OR 0.66, 95% CI 0.53-0.82). Patients switching to DOACs were more likely to have used selective serotonin reuptake inhibitors (HR 1.64, 95% CI 1.13-2.37) than those remaining on VKAs. At 5 years, 31% of DOAC initiators and 9% of VKA initiators remained persistent. Only few patients were diagnosed with ischemic stroke or bleeding prior to treatment discontinuation. Conclusion: Most NVAF patients with liver disease initiated treatment with DOACs. Long-term persistence with DOACs was higher than with VKAs but remained relatively low

Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events:population based cohort study

Objective: To determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious renal events compared with either drug class alone among patients with type 2 diabetes, and to assess the effect of the combination on the individual components of major adverse cardiovascular events, heart failure, and all cause mortality. Design: Population based cohort study using a prevalent new-user design, emulating a trial. Setting: UK Clinical Practice Research Datalink linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases. Participants: Two prevalent new-user cohorts were assembled between January 2013 and December 2020, with follow-up until the end of March 2021. The first cohort included 6696 patients who started GLP-1 receptor agonists and added on SGLT-2 inhibitors, and the second included 8942 patients who started SGLT-2 inhibitors and added on GLP-1 receptor agonists. Combination users were matched, in a 1:1 ratio, to patients prescribed the same background drug, duration of background drug, and time conditional propensity score. Main outcome measures: Cox proportional hazards models were fitted to estimate the hazard ratios and 95% confidence intervals of major adverse cardiovascular events and serious renal events, separately, comparing the GLP-1 receptor agonist-SGLT-2 inhibitor combination with the background drug, either GLP-1 receptor agonists or SGLT-2 inhibitors, depending on the cohort. Secondary outcomes included associations with the individual components of major adverse cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular mortality), heart failure, and all cause mortality. Results: Compared with GLP-1 receptor agonists, the SGLT-2 inhibitor-GLP-1 receptor agonist combination was associated with a 30% lower risk of major adverse cardiovascular events (7.0 v 10.3 events per 1000 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and a 57% lower risk of serious renal events (2.0 v 4.6 events per 1000 person years; hazard ratio 0.43, 0.23 to 0.80). Compared with SGLT-2 inhibitors, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a 29% lower risk of major adverse cardiovascular events (7.6 v 10.7 events per 1000 person years; hazard ratio 0.71, 0.52 to 0.98), whereas serious renal events generated a wide confidence interval (1.4 v 2.0 events per 1000 person years; hazard ratio 0.67, 0.32 to 1.41). Secondary outcomes generated similar results but with wider confidence intervals. Conclusions: In this cohort study, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a lower risk of major adverse cardiovascular events and serious renal events compared with either drug class alone

Epidemiological study of childhood onset multiple sclerosis : course, prognosis and biases

The course and prognosis of childhood onset multiple sclerosis (MS) is not well defined unlike that with adult onset.A cohort of 380 patients with childhood onset (before the age of 16) MS and 3367 with adult onset were identified through the European Database for Multiple Sclerosis. The median time to reaching scores of four and six on the disability status scale was longer for childhood onset MS patients (20 and 29 years) compared with adult onset patients (12.8 and 23.7 years; p<0.0001). Two years after onset, the main prognostic factors of disability in childhood onset MS patients were age at onset, gender and the number of relapses during the first two years of MS. We showed that immortal time bias explains the previously reported protective effect of the time between the first two relapses on disability.Childhood onset MS has a slower evolution to disability than adult onset MS

Mitoxantrone et sclérose en plaques (efficacité et tolérance chez 123 patients)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Trends in new prescription of gabapentinoids and of coprescription with opioids in the 4 nations of the UK, 1993–2017

We explored potential differences in time trends of gabapentinoid prescription and of opioid coprescription between 1993 and 2017 in the 4 UK nations using the Clinical Practice Research Datalink, a UK primary care database. There were distinct trends in annual rates of new gabapentin and pregabalin prescriptions in Northern Ireland. The rate of new gabapentin prescriptions rapidly increased after 2010 and exceeded that of the other nations by 2017 (rate of 836 [95% confidence interval: 787-887] per 100 000 person-years). Additionally, the rate of new pregabalin prescriptions was higher during the entire study period, reaching a peak of 1139 (95% confidence interval: 1088-1193) per 100 000 person-years in 2010, 5-fold higher than the other nations. Findings in Northern Ireland may be partly attributable to the high burden of anxiety disorders, an indication for pregabalin. Further exploration of reasons for discrepancies in gabapentinoid prescribing between UK nations is warranted

Data from: Degree of serotonin reuptake inhibition of antidepressants and ischemic risk: a cohort study

Objective: To assess whether the use of antidepressants with strong inhibition of serotonin reuptake is associated with a decreased incidence of ischemic stroke and myocardial infarction (MI). Methods: We conducted a cohort study using the United Kingdom Clinical Practice Research Datalink and considering new users of selective serotonin reuptake inhibitors (SSRIs) or third-generation antidepressants aged ≥18 years between 1995 and 2014. Using a nested case-control approach, each case of a first ischemic stroke or MI identified during follow-up was matched with up to 30 controls on age, sex, calendar time, and duration of follow-up. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) of each outcome associated with current use of strong compared with weak inhibitors of serotonin reuptake using conditional logistic regression. Results: The cohort included 938,388 incident users of SSRIs (n = 868,755) or third-generation antidepressants (n = 69,633). Mean age at cohort entry was 46 years (64% women). During follow-up, 15,860 cases of ischemic stroke and 8626 cases of MI were identified and matched to 473,712 and 258,022 controls, respectively. Compared with current use of weak inhibitors of serotonin reuptake, current use of strong inhibitors was associated with a decreased rate of ischemic stroke (RR, 0.88; 95% CI 0.80-0.97), but the effect size was smaller in some sensitivity analyses. The rate of MI was similar between strong versus weak inhibitors (RR, 1.00; 95% CI, 0.87-1.15). Conclusion: Our large population-based study suggests that antidepressants strongly inhibiting serotonin reuptake could modestly decrease the rate of ischemic stroke

The role of the excess weight status in the risk of hospitalizations for patients with depression prescribed obesogenic antidepressants

Puzhko S, Schuster T, Renoux C, Barnett TA, Munro K, Bartlett-Esquilant G. The role of the excess weight status in the risk of hospitalizations for patients with depression prescribed obesogenic antidepressants. Pharmacoepidemiology and Drug Safety . 2022;31(Suppl. 2):424-425