Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Other

If ‘other’, further details on the scope of the study

Evaluation of posisble difference in renal function decline under rivaroxaban and warfarin chronic treatment

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Case-control
Cohort
Study drug and medical condition

Study drug International non-proprietary name (INN) or common name

RIVAROXABAN

Anatomical Therapeutic Chemical (ATC) code

(B01AA03) warfarin
warfarin

Additional medical condition(s)

Non-Valvular Atrial fibrillation
Population studied

Short description of the study population

Patients with NVAF newly initiated on OAC therapy with either rivaroxaban or a VKA.

Inclusion criteria
• aged ≥18 years in the IMRD-UK database
• a first prescription for either rivaroxaban or a VKA between 01 January 2014 and 31 March 2019. The date of the first rivaroxaban/VKA prescription will be set as the start date (start of follow-up for that patient). The follow-up will be extended until 30 September 2019 to ensure that each patient has at least 6 months of
potential follow-up.
• A diagnosis of AF recorded any time before start date or within 2 weeks after start date.
• Registered with their general practice at least 1 year before the start date and have a recorded prescription of any drug at least 1 year before the start date.
• Registered with a general practice with data considered to be up-to-standard quality.

Exclusion criteria
• A prescription for any OAC before the start date – all first-time rivaroxaban/VKA users will therefore be OAC naïve
• A record of heart valve replacement or mitral stenosis any time before the start date or in the 2 weeks after the start date.
• A record of deep vein thrombosis, pulmonary embolism, or hip/knee surgery in the 3 months before the start date (because these are all alternative reasons for NOAC initiation
• A record of ESRD (including renal transplant patients) on/before the start date

Age groups

  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)
      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)

Special population of interest

Other

Special population of interest, other

Atrial fibrillation patients

Estimated number of subjects

25000
Study design details

Main study objective

To estimate the magnitude of renal decline, incidence of end-stage renal disease (ESRD) and acute kidney injury (AKI) in patients with NVAF treated with rivaroxaban and those treated with a VKA according to the presence of CKD and its severity at the start of OAC therapy in UK primary care

Outcomes

- %change in serum creatinine - doubling of serum creatinine - rate of eGFR change - %eGFR change - incidence of ESRD and AKI

Data analysis plan

Cohort analyses: The difference in the eGFR slopes after initiation between patients starting on rivaroxaban and on a VKA will be assessed using a linear mixed regression model. Only individuals with at least two recorded eGFR measurements after treatment initiation will be included in this analysis. Incidence rates of each adverse renal outcome will be calculated with 95% CIs assuming a Poisson distribution. Incidence rates will be stratified by age-group, sex, CKD stage at baseline, the starting OAC, and for rivaroxaban, the dose of the starting prescription (20 mg/day or 15 mg/day). A survival analysis using Cox proportional hazard regression, will be performed to compare the time to the occurrence of the study outcomes according to the starting OAC. Case–control analyses: Unconditional logistic regression will be used to ORs with 95% CIs to estimate the associations between current exposure to rivaroxaban/VKA and and the study outcomes adjusted for confounders