Statin use to mitigate the unwarranted cardiovascular side effects of non-steroidal anti-inflammatory drugs: A population-based case control study

Date of Approval: 
2020-12-18 00:00:00
Lay Summary: 
Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are some of the most commonly taken drugs around with world with around 20% of people in the UK taking them at any one time. NSAIDs are good at treating inflammation and pain and can prevent some cancers but they increase a person’s chance of having a heart attack or a stroke by as much as 30%. It is surprising that given the scale of use, we currently do not know: 1) If NSAID use is an independent risk factor of cardiovascular disease. 2) Enough about what groups of patients have the highest risk. 3) If there are any treatments to reduce the risk. We want to therefore conduct a large population based study to try and address these questions in patients in routine clinical care. We hope that this study will give researchers and clinicians around the world a better understanding of what groups of patients are at the highest risk and highlight potential treatment options to reduce this risk.
Technical Summary: 
Non-steroidal anti-inflammatory drugs (NSAIDs) which include ibuprofen, naproxen and celecoxib, are amongst the most commonly used medications world-wide to treat fever, pain and inflammation. With the exception of aspirin, all NSAIDs carry a significant risk of heart attacks and strokes which has led to increased anxiety amongst physicians and patients and the withdrawal of celecoxib as a preventive treatment for colon cancer. Despite the widespread use of NSAIDs, we currently do not know: 1) If NSAID use is an independent risk factor of cardiovascular disease. 2) Enough about what groups of patients have the highest risk. 3) If there are any treatments to reduce the risk. Our objective is to identify risk factors that might predict cardiovascular events in patients who take NSAIDs. We want to assess whether cardio-protective drugs including statins or aspirin may be protective against additional cardiovascular disease associated with NSAID use. Our study will be split into three stages: Stage 1: To identify whether NSAID use is an independent risk factor for cardiovascular disease we will use a matched case control study to identify predictors of cardiovascular disease (myocardial infarctions and strokes (excluding TIAs) using conditional logistic regression. Stage 2: To identify what group of NSAID users are at the highest risk of a cardiovascular event we will identify risk factors for myocardial infarction or stroke in NSAID users using time to event data. We will use cox-regression. We hope this could allow clinicians to risk stratify patients who require longer-term NSAID use. Stage 3: We will assess if aspirin or statin use as a secondary preventative measure can offset the additional cardiovascular risk associated with NSAID use, again using Cox regression.
Health Outcomes to be Measured: 
Myocardial infarction which will include STEMI, NSTEMI and Acute coronary syndromes as a composite outcome and if numbers allow individually. Stroke which will include ischaemic and haemorrhagic but not TIA given the inaccuracy of recording of TIA events. Codes will be used according to the stroke validation study undertaken (Morgan et al Br J GP 2020). We will identify these outcomes in HES and ONS so death by these causes will be included. If numbers allow we will look at mortality separately as an outcome.
Application Number: 
20_000170
Collaborators: 

Jennifer Quint - Chief Investigator - Imperial College London
Ricky Vaja - Corresponding Applicant - Imperial College London
Jane Mitchell - Collaborator - Imperial College London
Laura Portas - Collaborator - Imperial College London
Nicholas Kirkby - Collaborator - Imperial College London
Plinio Ferreira - Collaborator - Imperial College London

Linkages: 
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation