Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015).

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

Risk of venous thromboembolism among users of different anti-osteoporosis drugs: a population-based cohort analysis including over 200,000 participants from Spain and the UK.

The venous thromboembolism risk among anti-osteoporotics is unknown. In this primary care study, the risk with other bisphosphonates [1.05 (0.94-1.18) and 0.96 (0.78-1.18)], strontium [0.90 (0.61-1.34) and 1.19 (0.82-1.74)], in the UK and Spain respectively, and denosumab [1.77 (0.25-12.66)] and teriparatide [1.27 (0.59-2.71)] in Spain, did not differ versus alendronate. INTRODUCTION: Most of the known adverse drug reactions described for anti-osteoporosis medication (AOM) have been described in studies comparing AOM users to non-users. We aimed to compare the risk of venous thromboembolism (VTE) among incident users of different AOM compared to alendronate (first line therapy). METHODS: Two cohort studies were performed using data from the UK (CPRD) and Spain (BIFAP) primary care records separately. All patients aged ≥ 50 years with at least 1 year of data available and a new prescription or dispensation of AOM (date for therapy initiation) during 2000-2014 (CPRD) or 2001-2013 (BIFAP) were included. Users of raloxifene/bazedoxifene were excluded from both databases. Five exposure cohorts were identified according to first treatment: (1) alendronate, (2) other bisphosphonates, (3) strontium ranelate, (4) denosumab, and (5) teriparatide. Participants were followed from the day after therapy initiation to the earliest of a treated VTE (cases), end of AOM treatment (defined by a refill gap of 180 days), switching to an alternative AOM, drop-out, death, or end of study period. Incidence rates of VTE were estimated by cohort. Adjusted hazard ratios (HR 95%CI) were estimated according to drug used. RESULTS: Overall, 2035/159,209 (1.28%) in CPRD and 401/83,334 (0.48%) in BIFAP had VTE. Compared to alendronate, adjusted HR of VTE were 1.05 (0.94-1.18) and 0.96 (0.78-1.18) for other bisphosphonates, and 0.90 (0.61-1.34) and 1.19 (0.82-1.74) for strontium in CPRD and BIFAP, respectively; 1.77 (0.25-12.66) for denosumab and 1.27 (0.59-2.71) for teriparatide in BIFAP. CONCLUSIONS: VTE risk during AO therapy did not differ by AOM drug use. Our data does not support an increased risk of VTE associated with strontium ranelate use in the community.

Validation and incidence of community-acquired pneumonia in patients with type 2 diabetes in the BIFAP database.

Oral anti-diabetic drugs (OADs) have been associated with community-acquired pneumonia (CAP). We aimed to validate the recording of CAP in the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) for the future evaluation of OAD-CAP association. The incidence rate (IR/1000 person-years) of CAP in type 2 diabetes mellitus (T2DM) was also determined. In total, 2966 pneumonia records (2040 listed as diagnosis and 926 as identified from comments added by physicians) were identified from 76 009 patients with T2DM after the first OAD in 2002-2013. Data around the CAP date were reviewed: 1803 (60·9%) were classified as 'probable CAP' (confirmed by X-ray/laboratory, referral letters or CAP lung site); 589 (19·8%) as 'no-case' (486 had other illness, 78 previous CAP, 25 cancer); and 574 (19·4%) as 'possible CAP' (441 without confirmatory information, 133 with uncertain diagnosis or uncertain diagnosis date). In total, 74·2% and 31·4% of pneumonia records in the diagnosis and comments, respectively, were 'probable cases' (IR: 6·04), which increased to 90·5% and 42·9%, respectively, when the 441 'possible cases' without confirmatory information were included (IR: 7·52). In summary, diagnosis had a high positive predictive value, and adding cases automatically detected from comments decreased that value significantly.

Risk factors for diabetic macular oedema in type 2 diabetes: A case-control study in a United Kingdom primary care setting.

AIM: To identify risk factors associated with the development of DMO among patients diagnosed with type 2 diabetes managed in a primary care setting in the UK. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000-2007. Cases were people with DMO (N=211) and controls were a DMO-free sample (N=2194). No age restrictions were applied. Adjusted odds ratios and 95%CIs were estimated (OR; 95%CI). RESULTS: DMO increased with high alcohol use (2.88; 1.49-5.55), cataracts (4.10; 2.73-6.15), HbA1c ≥7% (1.58; 1.08-2.32), systolic blood pressure ≥160mm Hg (2.03; 1.17-3.53), total cholesterol ≥5mmol/L (1.66; 1.15-2.39), LDL ≥3mmol/L (1.73; 1.14-2.61), and microalbuminuria (1.78; 1.16-2.73). Diuretic drugs were associated with a reduced risk of DMO (0.68; 0.47-0.99), as did smoking (0.47; 0.28-0.77), overweight (0.53; 0.30-0.96) or obesity (0.52; 0.30-0.91) at diabetes diagnosis, and high triglyceride levels (0.51; 0.35-0.74). Patients treated with anti-diabetic drugs showed higher risk of DMO than non-treated patients, particularly those with sulphonylureas (3.40; 2.42-4.78), insulin (3.21; 1.92-5.36) or glitazones (1.88; 1.17-3.04). CONCLUSION: In patients with type 2 diabetes managed in primary care, multiple factors associated with DMO were identified, such as cataracts, microalbuminuria and high levels of HbA1c, systolic BP, total cholesterol, and LDL. Diuretic drugs were associated with a reduced risk of DMO. Treated diabetes, particularly with sulphonylureas, insulin or glitazones showed highest risk of DMO. The inverse association between smoking, obesity, and triglycerides and DMO deserves further research.

Depression and treatment with antidepressants are associated with the development of gastro-oesophageal reflux disease.

BACKGROUND: The roles of depression and antidepressants in triggering reflux symptoms remain unclear. AIM: To compare the incidence of gastro-oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. METHODS: The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age- and sex-matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow-up of 3.3 years. Furthermore, we performed nested case-control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. RESULTS: The incidence of GERD was 14.2 per 1000 person-years in the depression cohort and 8.3 per 1000 person-years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60-1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34-2.20), while selective serotonin reuptake inhibitors were not associated with GERD. CONCLUSIONS: A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.