Which is more cardiotoxic, Diclofenac (Non-Steroidal Anti-Inflammatory Drug, NSAID) or Celecoxib (Cyclooxygenase-2, COX-2 inhibitor)?

From the Guidelines

Diclofenac is generally considered more cardiotoxic than Celecoxib. Among NSAIDs, diclofenac carries one of the highest cardiovascular risks, with studies showing it increases the risk of major cardiovascular events by approximately 40-60% compared to non-use 1. Celecoxib, particularly at lower doses, demonstrates a more favorable cardiovascular safety profile. The difference in cardiotoxicity relates to how these medications affect the balance between thromboxane and prostacyclin. Diclofenac strongly inhibits both COX-1 and COX-2 enzymes, disrupting this balance more significantly and promoting platelet aggregation, vasoconstriction, and potentially thrombosis. Celecoxib, being more selective for COX-2, causes less disruption to this balance. However, all NSAIDs carry some degree of cardiovascular risk, which increases with higher doses and longer duration of use. For patients with existing cardiovascular disease, the safest NSAID option would be naproxen, while celecoxib at lower doses represents a reasonable alternative when COX-2 selectivity is desired. The cardiovascular risk of both medications increases with dose and duration, so using the lowest effective dose for the shortest necessary period is recommended. Key points to consider include:

• The American Heart Association has issued warnings regarding the cardiovascular risks associated with NSAIDs, including both non-selective NSAIDs like diclofenac and COX-2 inhibitors like celecoxib 1.
• The choice between diclofenac and celecoxib should be made with consideration of the patient's individual risk factors for cardiovascular disease.
• Monitoring for signs of cardiovascular events is crucial when prescribing either of these medications.

From the Research

Comparison of Cardiotoxicity

• Diclofenac and Celecoxib are both associated with increased cardiovascular risks, but the extent of their cardiotoxicity can be compared through various studies:
  • A study published in 2009 2 found that diclofenac had a higher risk of serious coronary heart disease compared to naproxen, with an incidence rate ratio of 1.86 (1.18-2.92) for short-term use.
  • Another study from 2022 3 compared the cardiovascular risks of diclofenac with other COX-2 inhibitors, including celecoxib, and found that diclofenac had a similar increased risk of major adverse cardiovascular events (MACE) compared to celecoxib, with an adjusted intention-to-treat incidence rate ratio of 1.02 (0.88-1.19) for celecoxib.
  • A 2020 study 4 found that diclofenac was associated with a relatively higher risk of myocardial infarction (MI) compared to other NSAIDs, but this risk decreased with increasing baseline cardiovascular risk.

Relative Cardiotoxicity

• The relative cardiotoxicity of diclofenac and celecoxib can be summarized as follows:
  • Diclofenac may have a higher risk of serious coronary heart disease compared to celecoxib, especially at high doses 2, 3.
  • Celecoxib has been found to have a similar increased risk of MACE compared to diclofenac 3.
  • The cardiovascular safety of celecoxib has been demonstrated to be noninferior to ibuprofen or naproxen at moderate doses 5.

Key Findings

• The key findings from the studies can be summarized as follows:
  • Diclofenac is associated with an increased risk of serious coronary heart disease and MACE 2, 3.
  • Celecoxib has a similar increased risk of MACE compared to diclofenac 3.
  • The cardiovascular safety of celecoxib is noninferior to ibuprofen or naproxen at moderate doses 5.