Date of Approval:
Blood clots which occur in the veins of the legs or in the lungs, also known as venous thromboembolism (VTE), continue to pose important health problems, however a lot remains unknown about what causes them. In recent years, more attention is being focused on medications that play a role in the development of this disease. A significant proportion of the adult population receives drugs known as statins for ongoing treatment of elevated levels of bad cholesterol. Because statin use is common, it is important to understand serious adverse effects or beneficial effects of statins. The objective of this study is to determine whether statin use lowers the risk of VTE.
Venous thromboembolism (VTE) poses an important disease burden, however a lot remains unknown about risk factors associated with it. Over 25% of Americans >40 years old take statins to treat hypercholesterolemia, particularly patients with other cardiovascular risk factors, and the lipid-lowering effect of statins has been shown to significantly reduce the risk of arterial embolic events12-14. In contrast, randomized and non-randomized studies evaluating the relationship between statin therapy and VTE outcomes have found conflicting results11;15-41. Thus, additional studies are needed to investigate this potential association. This will be a cohort study among adults during 1995-2017 in the UK-based CPRD. To be included, patients must have; 1)at least one diagnosis of dyslipidaemia, 2)at least one statin or fibrate prescription, 3)at least one year of history in the CPRD before the statin or fibrate prescription, 4)no prior diagnoses of CKD, vasculitis or coagulopathy and 5)no diagnoses of cancer (except non-melanoma skin cancer). Exposed patients will be patients with >=3 statin prescriptions and will be matched by propensity scores to patients with only fibrate prescriptions or <3 statin prescriptions in their record. We will follow both cohorts until the development of VTE, death, end of CPRD record, or end of the study period, whichever comes first. Based on the feasibility analyses, we will not be able to compare statin-only to fibrate-only users due to the relatively low number of fibrate-only users when compared to statin-only users. Using descriptive analyses and Cox proportional hazard models, we will evaluate the relationship between the risk of VTE and statin exposure, in relation to timing, duration of use, number, and dose of statin prescriptions. The proposed study will efficiently evaluate the safety/benefits of statins, which will guide the development of guidelines for its use in the care of patients with hypercholesterolemia and cardiovascular disease risk.
Health Outcomes to be Measured:
The outcome will be incident idiopathic VTE (DVT and PE. Using Read codes, we will identify the first record of an incident VTE diagnosis in the medical record after study entry (the date of first statin or fibrate prescription). Idiopathic VTE cases will be defined as any VTE case that does not have a code for a proximate cause of VTE (such as surgery, trauma, see below) recorded in the CPRD within 90 days prior to the VTE diagnosis date. We will employ this criterion because, if there is an effect of statin use on VTE, including non-idiopathic VTE cases could dilute the true effect of the statin, (because it is unlikely that there is an effect of the drug in non-idiopathic cases where the VTE is triggered by another cause) and exposure is likely to reflect the exposure in the base population. Proximate causes of VTE include pregnancy, immobility, prolonged hospitalization, fractures, multiple trauma, orthopaedic surgery involving long bones or pelvis and, other major surgery. Any participant with a VTE that occurs after a proximate cause will be retained in the study sample, however they will not be considered a case in this study since they do not meet the case definition of idiopathic VTE. To validate the VTE diagnosis we will require that all cases receive a prescription for an anticoagulant (including unfractionated heparin, low-molecular-weight heparins (LMWH) and fondaparinux) present after the VTE diagnosis. VTE codes and anticoagulants are provided in Appendix 1 and Appendix 2, respectively. We will also consider adding other new anticoagulants and antiplatelet drugs. VTE codes are provided in Appendix 1.
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Susan Jick - Corresponding Applicant - BCDSP - Boston Collaborative Drug Surveillance Program
Lade Ayodele - Collaborator - Decision Resources Group