Unintended effects of novel oral anticoagulants (NOAC) vs warfarin in real world settings

Date of ISAC Approval: 
Lay Summary: 
Anticoagulants (also called 'blood thinning' agents) are used both to treat blood clots and to help prevent further blood clots and stroke in people with previous history of those, people with irregular heartbeats or after hip/knee replacement operations. Warfarin is a medicine also used to treat blood clots and to prevent strokes, but it can cause problems for some patients. It needs ongoing blood tests and can cause bleeding - such as vomiting or coughing up blood - which may need hospital care or even be fatal. Some new anticoagulants, which may not need blood tests, now exist, but they are quite expensive. It is also unclear how safe these treatments will be in the longer term since the original trials were done over relatively short periods of time (only up to 2 years) and because trials were done using selected patients, who may be different from patients in real world settings. We need, therefore, to research the safety of the new anticoagulants when compared with the older ones over longer periods of time and in normal clinical practice. Because of their novelty, the drugs are not widely prescribed and the adverse effects are also rare. Their study will require a very large number of patient records - available only from routinely-collected primary care data.
Technical Summary: 
Objective: The study will compare in patients prescribed different types of novel anticoagulant drugs (NOAC) the risks of major bleeding requiring hospitalisation with those in patients prescribed warfarin. Methods: This will be a cohort study following patients who received anticoagulant prescription (NOAC or warfarin) between 1 September 2008 and 1 September 2016. We will use new-user design so patients with anticoagulant prescriptions in the previous 12 months will be excluded. Outcomes will be hospitalisations and deaths identified from HES and ONS mortality data. Primary outcomes will include gastrointestinal and intracranial bleed. Secondary outcomes will include ischaemic stroke and venous thromboembolism (VTE). Analysis: Exposure to different NOAC (dabigatran, rivaroxaban and apixaban) will be compared with exposure to warfarin using a Cox regression analysis. The results will be adjusted for potential confounders evaluated at the date of the first prescription.
Health Outcomes to be Measured: 
- Incidence of major bleeding - Ischaemic stroke - Venous thromboembolism - minor bleeding - all-cause mortality

Professor Julia Hippisley-Cox - Chief Investigator - University Of Oxford
Carol Coupland - Collaborator - University Of Nottingham
Yana Vinogradova - Collaborator - University Of Nottingham
Yana Vinogradova - Corresponding Applicant - University Of Nottingham

HES Admitted;ONS;Patient Townsend