Dana Alameddine, Alessandro Squizzato, Nicoletta Riva, Cassius I. Chaar Ochoa.
Response/Recommendation: There is not enough evidence to support the use of non-steroidal anti-inflammatories (NSAID) as sole pharmacological agents to prevent venous thromboembolism (VTE) in patients undergoing orthopaedic surgery.
Strength of Recommendation: Limited.
Rationale: There is a risk of developing VTE in patients who undergo any major surgery. Since VTE can be a potentially life-threatening complication, thromboprophylaxis is commonly administered to patients at high-risk1,2. There is very limited literature examining the use of NSAID as prophylaxis against VTE post-orthopaedic surgery.
A systematic review of the literature was conducted. The published studies report conflicting results related to this specific question. A few studies reported that the use of NSAID, in patients undergoing orthopaedic surgeries, is associated with a decrease in the risk of post-operative VTE. One prospective clinical study showed that the use of indomethacin significantly decreased the prevalence of symptomatic and asymptomatic deep venous thrombosis (DVT) in patients undergoing total knee arthroplasty (TKA) compared to patients not receiving indomethacin. It was postulated that the effect is related to the role of NSAID in inhibiting platelet aggregation, and in decreasing the serum levels of thromboxane A2, and thus its metabolite thromboxane B23.
In two other studies, the incidence of VTE after TKA was compared between patients with rheumatoid arthritis (RA) and osteoarthritis. The studies showed that the incidence of DVT was lower in patients treated for RA. However, when patients treated with NSAID for RA were excluded, the incidence of VTE was no different between the 2 groups. The authors postulated that the administration of NSAID in patients with RA is providing some protection from developing VTE2,4.
On the contrary, a study that enrolled patients who underwent a major orthopaedic surgery, showed that the occurrence of venous and arterial thromboembolic events was similar in those who took NSAID and those who did not. It compared a group of patients who received rivaroxaban along with NSAID, to a group who received rivaroxaban only. The study also divided patients into a group that was administered any one of the following: low-molecular-weight heparin, unfractionated heparin, fondaparinux, dabigatran etexilate, acetylsalicylic acid or vitamin K antagonists, along with NSAID, and compared it to a group who took the listed medications but was not on NSAID. It was found that whether NSAID were given or not, the incidence of VTE was the same; therefore, the study concluded that NSAID did not have an influence on the incidence of VTE after orthopaedic surgery5.
Finally, and as shown in different studies, a case report re-emphasized the interaction of NSAID, as pain medications, with aspirin, as VTE prophylactic agents, in patients who underwent orthopaedic surgery. It was suggested that the concomitant use of those two medications resulted in an increase in post-operative VTE incidences. This was presumed because NSAID competitively inhibits aspirin (ASA) at its site of action. Therefore, the authors recommended that NSAID should be taken two hours prior to ASA6.
References:
1. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001;119(1 Suppl):132S-175S. doi:10.1378/chest.119.1_suppl.132s
2. Niki Y, Matsumoto H, Hakozaki A, Mochizuki T, Momohara S. Rheumatoid arthritis: a risk factor for deep venous thrombosis after total knee arthroplasty? Comparative study with osteoarthritis. J Orthop Sci. 2010;15(1):57-63. doi:10.1007/s00776-009-1410-3
3. Wang C-J, Wang J-W, Weng L-H, Hsu C-C, Huang C-C, Yu P-C. Prevention of deep-vein thrombosis after total knee arthroplasty in Asian patients. Comparison of low-molecular-weight heparin and indomethacin. J Bone Joint Surg Am. 2004;86(1):136-140. doi:10.2106/00004623-200401000-00020
4. van Heereveld HA, Laan RF, van den Hoogen FH, Malefijt MC, Novakova IR, van de Putte LB. Prevention of symptomatic thrombosis with short term (low molecular weight) heparin in patients with rheumatoid arthritis after hip or knee replacement. Ann Rheum Dis. 2001;60(10):974-976. doi:10.1136/ard.60.10.974
5. Kreutz R, Haas S, Holberg G, et al. Rivaroxaban compared with standard thromboprophylaxis after major orthopaedic surgery: co-medication interactions. Br J Clin Pharmacol. 2016;81(4):724-734. doi:10.1111/bcp.12836
6. Krauss E, Cronin M, Dengler N, Segal A. Interaction Between Low-Dose Aspirin and Nonsteroidal Anti-Inflammatory Drugs Can Compromise Aspirin’s Efficacy in Preventing Venous Thrombosis Following Total Joint Arthroplasty. Clin Appl Thromb Hemost. 2020;26:1076029620920373. doi:10.1177/1076029620920373