non-steroidal anti-inflammatory drugs (NSAIDs) and venous thromboembolism (VTE)

Last edited 09/2023 and last reviewed 09/2023

Non-steroidal anti-inflammatory drugs (NSAIDs) and venous thromboembolism (VTE)

Selective or non-selective NSAIDs two-fold or greater increase the risk of venous thromboembolism (1)

• NSAIDs increase the risk of not only venous but also arterial thromboembolism (1)
  • PGI2 inhibition, which has an antithrombotic effect with COX-2 inhibition, may increase the thrombosis risk
  • both use of traditional NSAIDs, such as ibuprofen, diclofenac, and naproxen, and use of newer highly selective cyclo-oxygenase-2 inhibitors have been linked to an increased risk of both arterial and venous thromboses (2)
  • thrombosis tendency is higher in COX-2 selective inhibitors
    • via their targeted inhibition of cyclo-oxygenase enzymes, NSAIDs promote platelet aggregation, which contributes to activation of the coagulation system and thereby potentially to the formation of a venous thrombosis (2)
    • COX-2 suppression disrupts thromboxane A2/PGI2 balance in favor of thromboxane A2
    • by suppressing COX-1 over 95%, an antithrombotic effect occurs
      
      
• Meaidi et al undertook a study to assess the influence of concomitant use of hormonal contraception and non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of venous thromboembolism
  • analysis of Danish registry data (2.0 million women followed for 21.0 -million-person years) found NSAID use linked to venous thromboembolism, the risk of which was significantly larger with concomitant use of high/medium risk vs. low/no risk hormonal contraception
  • NSAID use was positively associated with the development of venous thromboembolism in women of reproductive age
    • number of extra venous thromboembolic events with NSAID use compared with non-use was significantly larger with concomitant use of high/medium risk hormonal contraception compared with concomitant use of low/no risk hormonal contraception
      
    • authors state that "..women needing both hormonal contraception and regular use of NSAIDs should be advised accordingly.."
      
      
• in a study among patients with knee osteoarthritis the authors found:
  • among NSAIDs, the degree of VTE (venous thromboembolism) risk was dependent on the specific NSAID (3)
    • as compared with the 63% increase in the risk among current diclofenac users and 49% increase in current ibuprofen users, the risk was not increased at all among current naproxen users

Reference:

• Cumhur Cure M, Kucuk A, Cure E. NSAIDs may increase the risk of thrombosis and acute renal failure in patients with COVID-19 infection. Therapie. 2020 Jul-Aug;75(4):387-388. doi: 10.1016/j.therap.2020.06.012. Epub 2020 Jun 27. PMID: 32636031; PMCID: PMC7320673
• Meaidi A, Mascolo A, Sessa M, Toft-Petersen A P, Skals R, Gerds T A et al. Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study BMJ 2023; 382 :e074450 doi:10.1136/bmj-2022-074450
• Lee T, Lu N, Felson DT, Choi HK, Dalal DS, Zhang Y, Dubreuil M. Use of non-steroidal anti-inflammatory drugs correlates with the risk of venous thromboembolism in knee osteoarthritis patients: a UK population-based case-control study. Rheumatology (Oxford). 2016 Jun;55(6):1099-105