Damage to the brain caused by a blood clot is a leading cause of death in the developed world. One of the more important causes of blood clot is an abnormal heart rhythm, in which blood clots may form in the upper chamber of the heart. For many years a blood thinner called warfarin was the only medication that was used to prevent of stroke. Recently, a number of newer drugs called Direct Oral Anticoagulants have been approved. The studies that led to approval of these medications found that they were as effective and similar in safety compared to warfarin. However, these studies did not provide information on the effectiveness and safety of the newer drugs under special conditions that may elevate the concentration of the drug in the body. Examples of situations include female gender, advanced age, certain medications and patients with kidney damage.
We aim to assess the safety and effectiveness of the newer drugs under conditions that change drug concentrations. In this study, we will identify if certain medications, age, kidney damage, and gender are risk factors for bleeding in patients treated with the newer drugs compared to warfarin.
Primary objective: to assess the safety and effectiveness of direct oral anticoagulants antagonists in conditions that elevates drug concentrations: renal failure, female gender and specific drugs.
Methods: This study will use the CPRD database, the HES and the ONS mortality data. The study has been designed as cohort study on patients with a diagnosis of AF. The index date will be defined as the first prescription to anticoagulant (DOACS/VKA). The cohort will be restricted to those eligible for linkage with HES and ONS mortality data. Patients will be followed from index date until the earliest of the respective outcome of interest (stroke, systemic embolism, intracranial bleeding, death from any cause, gastrointestinal bleeding, traumatic intracranial bleeding, major bleeding and non-major clinically relevant bleeding), transfer out of the practice or last data collection. Special consideration will be given to participants with previous stroke, and their data will undergo a separate analysis.
Cohort study data analysis: time-varying approach.Cox proportional hazard models.
The primary outcome for inducers will be stroke and systemic embolism. The primary outcome for inhibitors will be major bleeding.
Ilan Matok - Chief Investigator - The Hebrew University of Jerusalem
Ilan Matok - Corresponding Applicant - The Hebrew University of Jerusalem
Amichai Perlman - Collaborator - The Hebrew University of Jerusalem
Bruria Raccah - Collaborator - The Hebrew University of Jerusalem
Donna R. Zwas - Collaborator - The Hebrew University of Jerusalem
HES Admitted Patient Care;ONS Death Registration Data