PurposeAn important element of risk management is the planning and implementation of risk minimisation measures (RMMs) and the evaluation of their effectiveness by process or outcome indicators. The aim of this review is to summarize the characteristics of risk minimisation (RM) effectiveness studies in Europe and provide an overview of RMMs and their effectiveness.MethodsThis was a qualitative review of RM effectiveness studies in the European Union electronic Register of Post‐Authorization Studies (EU PAS Register); data extracted included study design, population, sample size, data sources, drug information, RMMs, study period, indicators, and their reported effectiveness.ResultsOf the 872 records in the EU PAS Register, 19 studies evaluating the effectiveness of RMMs were included. Eleven were cross‐sectional surveys and 8 used secondary data sources. Eighty‐nine percent (17/19) evaluated additional RMMs (used when routine RMMs are considered insufficient), and 36% (7/19) evaluated changes in routine RMMs (applicable to all medicinal products). A total of 42 effectiveness indicators were identified: 18 process and 24 outcomes. Half of the indicators (21/42) were successful; 2% (1/42) indicators were partially successful; 17% (7/42) indicators were inconclusive. Effectiveness of the remaining 31% (13/42) indicators could not be determined owing to limited information. The United Kingdom was the most frequent country for the conduct of RM effectiveness studies.ConclusionsMost of the included studies evaluated additional RMMs. Half of the effectiveness indicators (process and/or outcome) were reported as successful. This review provides evidence to support the development of future guidance on the effectiveness of RM in Europe.

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ObjectiveTo evaluate the appropriateness of the initial prescribed daily dose of non-vitamin K antagonist oral anticoagulants (NOACs) according to label in patients with non-valvular atrial fibrillation (NVAF) in the UK.DesignPopulation-based cross-sectional study.SettingUK primary care.Population30 467 patients with NVAF and a first prescription for apixaban, dabigatran or rivaroxaban between January 2011 and December 2016.Main outcome measuresPercentage of patients prescribed a NOAC dose according to the European Union (EU) labels (appropriately dosed), and not according to the EU labels (inappropriately dosed—including both underdosed and overdosed patients); percentage of patients prescribed an initial NOAC dose according to renal function status.ResultsA total of 15 252 (50.1%) patients started NOAC therapy on rivaroxaban, 10 834 (35.6%) on apixaban and 4381 (14.4%) on dabigatran. Among patients starting NOAC therapy on rivaroxaban, 17.3% were eligible to receive a reduced dose compared with 12.8% of patients starting on apixaban and 53.8% of patients starting on dabigatran. The majority of patients were prescribed an appropriate dose according to the EU labels: apixaban 74.9 %, dabigatran, 74.4%; rivaroxaban, 84.2%. Underdosing occurred in 21.6% (apixaban), 8.7% (dabigatran), 9.1% (rivaroxaban). Overdosing was more frequent for dabigatran (16.9%) than for rivaroxaban (6.6%) or apixaban (3.5%). There was a trend towards dose reduction with increasing renal impairment. Among patients with severe renal impairment, the majority received a reduced dose NOAC: apixaban, 91.1%, dabigatran, 80.0%, rivaroxaban, 83.0%.ConclusionBetween 2011 and 2016, the majority of patients starting NOAC therapy in UK primary care were prescribed a daily dose in line with the approved EU drug label. Underdosing was more than twice as common among patients starting on apixaban than those starting on dabigatran or rivaroxaban. Research into the patient characteristics that may influence inappropriate underdosing of NOACs in UK primary care is warranted.

ObjectiveTo determine discontinuation rates, patterns of use and predictors of discontinuation of non-vitamin K antagonist oral anticoagulants (NOACs) among patients with non-valvular atrial fibrillation (NVAF) in the first year of therapy.DesignPopulation-based cohort study.SettingUK primary care.Population11 481 patients with NVAF and a first prescription (index date) for apixaban, dabigatran or rivaroxaban (January 2012 to December 2016) with at least 1 year of follow-up and at least one further NOAC prescription in the year following the index date were identified. 1 year rates and patterns of discontinuation were described.Primary and secondary outcome measuresOutcome measures were the percentage of patients who, in the first year from starting NOAC therapy, discontinued with their oral anticoagulant (OAC) therapy (discontinuation was defined as a gap in OAC therapy of >30 days); switched OAC within 30 days; discontinued and reinitiated OAC therapy. Predictors of discontinuation were also evaluated.Results1 year discontinuation rates according to the index NOAC were 26.1% for apixaban, 40.0% for dabigatran and 29.6% for rivaroxaban. Reinitiation rates were 18.1% for apixaban, 21.7% for dabigatran and 17.3% for rivaroxaban, and switching rates were 2.8% for apixaban, 8.8% for dabigatran and 4.9% for rivaroxaban. More than 93% of reinitiations were with the index NOAC. Patients starting on dabigatran were more likely to switch OAC therapy than those starting on apixaban; ORs 4.28 (95% CI 3.24 to 5.65) for dabigatran and 1.89 (95% CI 1.49 to 2.39) for rivaroxaban. Severely reduced renal function was a predictor of any discontinuation, OR 1.77 (95% CI 1.28 to 2.44).ConclusionWhile the majority of patients with NVAF in the UK initiating NOAC treatment received continuous therapy in the first year of treatment, a substantial proportion of patients experienced gaps in treatment leaving them less protected against thromboembolism during these periods.

IMPORTANCE Epidemiological data on lower gastrointestinal bleeding (GIB) in the general population are sparse. OBJECTIVE To describe the incidence, recurrence, mortality, and case fatality rates of major upper GIB and lower GIB in the general population of Finland between 1987 and 2016. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study used data from the 1987 to the 2012 cycles of the National FINRISK Study, a health examination survey that was conducted every 5 years in Finland. Survey participants were adults aged 25 to 74 years who were recruited from a population register by random sampling; those with a history of hospitalization for GIB were excluded. Participants were followed up from survey enrollment to onset of GIB that led to hospitalization, death from any cause, or study end (December 31, 2016). Follow-up was performed through linkage with national electronic health registers. Data were analyzed from February 1, 2019, to January 31, 2020. MAIN OUTCOMES AND MEASURES Incidence, recurrence, mortality, and case fatality rates for all, upper, lower, and unspecified GIB. Outcome measures were stratified by sex and age group. RESULTS Among the 39 054 participants included in the study, 494 (1.3%) experienced upper GIB (321 men [65.0%]; mean [SD] age, 52.8 [12.1] years) and 645 (1.7%) had lower GIB (371 men [57.5%]; mean [SD] age, 54.0 [11.7] years). The age-standardized incidence rate was 0.94 per 1000 personyears (95% CI, 0.85-1.04) for upper GIB and 1.26 per 1000 person-years (95% CI, 1.15-1.38) for lower GIB; the incidence was higher in men than in women. Between 1987 and 2016 the incidence rate of upper GIB remained mostly stable, ranging from 0.40 to 0.66 per 1000 person-years, whereas constant increases occurred in the incidence of lower GIB until the rate stabilized. The proportion of recurrent GIB events showed an increasing trend from 1987 to 2016. The upper GIB-specific mortality was higher (0.07 per 1000 person-years; 95% CI, 0.04-0.09) than the lower GIB-specific mortality (0.01 per 1000 person-years; 95% CI, 0.001-0.03). Case fatality was high for those with upper GIB (7.0%; 95% CI, 4.7-10.1) compared with those with lower GIB (0.4%; 95% CI, 0.1-1.3). Case fatality remained stable over the years but was higher in men (between 5% and 10%) than women (<2%) with GIB. CONCLUSIONS AND RELEVANCE This study found that the overall incidence rate of upper GIB was lower than the incidence of lower GIB, but the recurrence, mortality, and 28-day case fatality were higher in participants with upper GIB. These data can serve as a reference when putting into context the rates of drug-associated GIB and can inform efforts to improve GIB care and outcome and to prevent rebleeding or death for patients with major GIB.