Study type

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness
Effectiveness study (incl. comparative)
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(B01AA03) warfarin
warfarin
(B01AE07) dabigatran etexilate
dabigatran etexilate
(B01AF01) rivaroxaban
rivaroxaban
(B01AF02) apixaban
apixaban

Medical condition to be studied

Atrial fibrillation

Additional medical condition(s)

All frail patients with an inpatient or outpatient primary or secondary discharge diagnosis of non-valvular atrial fibrillation. Frail patients will be identified using the Hospital Frailty Risk Score (HFRS). HFRS, a score utilizing ICD-codes, was developed to identify patients at low (HFRS <,5), intermediate (HFRS 5-15) and high risk (HFRS >15) of frailty.
Population studied

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

30000
Study design details

Main study objective

(1) To present population characteristics and rates of effectiveness and safety outcomes among frail patients with non-valvular atrial fibrillation in Denmark according to OAC treatment regimen (no OAC, warfarin, or NOAC). (2) To investigate the comparative effectiveness and safety of NOACs versus warfarin in a Danish nationwide cohort of frail patients with non-valvular atrial fibrillation.

Outcomes

The primary effectiveness outcome is a diagnosis of stroke or systemic embolism. The primary safety outcome is major bleeding recorded as intracranial, gastro-intestinal, and major bleeding in various anatomical positions and reported in total as ‘any bleeding’. All-cause death was also included as an outcome.

Data analysis plan

Substudy 1: Patient baseline characteristics will be described for the overall study population and according to age (≥80 or <80). Cumulative incidence functions will be used to visualize how risk of outcomes evolve over time since AF diagnosis according to OAC regimen and age group using the Aalen–Johansen estimator assuming death as competing risk. The absolute risk of each study outcome according to OAC regimen and age group will be calculated at 1 year after AF diagnosis. Substudy 2: Patient baseline characteristics will be described for the study population according to baseline treatment group. To compare the risk of each endpoint among NOAC users with warfarin users reference), pooled logistic regression models will be used to estimate treatment effects by means of hazard ratios for the effectiveness and safety outcomes (both an ITT and PP approach). To allow an unbiased comparison of the treatment groups, we plan to use inverse probability of treatment weighting (IPTW).