Use of non-steroidal anti-inflammatory drugs and risk of acute myocardial infarction in patients undergone total hip or knee replacement surgery: a population-based cohort study

Date of ISAC Approval: 
23/05/2018
Lay Summary: 
Non-steroidal anti-inflammatory drugs (NSAIDs) provide relief in pain and inflammation. Despite these positive effects, the use of NSAIDs is also associated with an increased risk of heart attacks and bleeding in the gut. Naproxen however seems to be an exception, as studies with many participants could not demonstrate that naproxen increases the chance of heart attacks. The favorable profile of naproxen in patients with a previous heart attack is however questioned in patients using aspirin (which is often used to prevent heart attacks) as laboratory research stipulates that combining naproxen and aspirin might undermine the positive effects of aspirin. In order to answer the question whether naproxen is still favorable in patients using ASA, this study compares the incidence of heart attacks in patients using naproxen with or without ASA. We decided to answer this question in patients who underwent total hip or knee replacement as these patients often chronically use NSAIDs because of osteoarthritis and have (due to their disease) a higher risk of having heart attack.
Technical Summary: 
The objective is to compare the risk of acute myocardial infarction between different NSAIDs in patients with concomitant aspirin use. Within the CPRD, all adult patients with a primary total hip / knee replacement surgery will be selected. To eliminate distortions from the in hospital period, the first 6 postoperative months will be excluded from the analysis. The exposure of interest is use of different types of NSAID in patients concomitantly taking aspirin. Exposure will be assessed in a time-dependent manner. Adjusted Cox regression models will be used to derive relative risks for the association between NSAID plus aspirin use and the risk of acute myocardial infarction and all-cause mortality.
Health Outcomes to be Measured: 
Our primary outcome of interest will be an AMI. All patients will be followed from the index date until death, transfer out of the practice, THR / TKR revision, the end of data collection, or an AMI. AMI will be classified using CPRD READ codes (see Appendix II). For our secondary outcome of interest, we will follow patients up until all-cause mortality.
Collaborators: 

Frank de Vries - Chief Investigator - Utrecht University
Anthonius de Boer - Researcher - Utrecht University
Arief Lalmohamed - Researcher - UMC Utrecht
Bart JF van den Bemt - Researcher - Sint Maartenskliniek
Karin Lancee - Collaborator - Utrecht University