What is the comparison between naproxen (Nonsteroidal Anti-Inflammatory Drug) and diclofenac in terms of safety and efficacy?

Naproxen vs Diclofenac: Safety and Efficacy Comparison

Naproxen is safer than diclofenac in terms of cardiovascular risk, while both medications have similar efficacy for pain relief and inflammation reduction. 1, 2

Cardiovascular Safety Profile

• Diclofenac has a significantly higher cardiovascular risk compared to naproxen, with meta-analyses showing diclofenac increases risk of vascular events by 63% (RR 1.63,95% CI 1.12-2.37) versus placebo, while naproxen shows no significant increase (RR 0.92,95% CI 0.67-1.26) 1
• Diclofenac has been associated with increased risk of major coronary events (moderate effect) and serious upper gastrointestinal events (moderate effect) 1
• Naproxen has the best safety profile related to myocardial infarction among common NSAIDs, while diclofenac shows the worst safety profile with excessively increased risk for stroke, MI and major bleeding 3
• In patients with osteoarthritis, naproxen demonstrated lower cardiovascular risk (HR 1.20,95% CI 1.04-1.39) compared to diclofenac (HR 1.44,95% CI 1.36-1.54) 2
• Diclofenac lies on the more COX-2 selective end of the spectrum, which explains its higher thrombotic risk profile similar to COX-2 inhibitors 1

Gastrointestinal Safety Profile

• Both medications carry risks for gastrointestinal complications, but with different profiles:
• Naproxen is associated with a large increase in risk for serious upper gastrointestinal events, particularly in the first 6 months of treatment 1
• Diclofenac shows a moderate effect on risk for serious upper gastrointestinal events 1
• In the intermediate term, both diclofenac and naproxen are associated with large increases in risk for hepatic harms 1
• Risk factors for NSAID-related GI complications include increasing age, previous GI events, concomitant use of anticoagulation therapy or corticosteroids 1

Efficacy Profile

• Both naproxen and diclofenac demonstrate similar efficacy for pain relief and reduction of inflammation 4, 5
• Naproxen has been shown to be effective in reducing joint swelling, morning stiffness, and improving mobility in patients with rheumatoid arthritis, osteoarthritis, and other inflammatory conditions 4
• Diclofenac has a fast onset and long duration of action as an analgesic, and is effective in both acute and chronic painful and inflammatory conditions 5
• In juvenile chronic arthritis, both medications showed similar efficacy with no significant differences between them 6

Withdrawal Due to Adverse Events

• NSAIDs are associated with increased risk for withdrawal due to adverse events (WAE) versus placebo 1
• The magnitude of this risk is small for diclofenac and moderate for naproxen 1
• Side effects tend to be mild and typical of NSAIDs, but may occur with different frequencies between the medications 6

Dosing Considerations

• Both medications should be prescribed at the lowest effective dose for the shortest duration necessary to control symptoms 1
• For patients with cardiovascular risk factors, naproxen is preferred over diclofenac based on its more favorable cardiovascular safety profile 1, 2
• In patients with osteoarthritis, low-dose naproxen and ibuprofen were associated with the lowest risks of cardiovascular events compared to no NSAID use 2

Clinical Decision Algorithm

1. For patients with cardiovascular risk factors or established cardiovascular disease:

   • Prefer naproxen over diclofenac due to lower cardiovascular risk 1, 2
   • Consider acetaminophen, tramadol, or non-pharmacological approaches first if appropriate 1

2. For patients with gastrointestinal risk factors:

   • Consider co-therapy with proton pump inhibitors for either NSAID 1
   • Monitor for GI complications, especially during the first 6 months of treatment 1

3. For patients requiring long-term NSAID therapy:

   • Naproxen is generally safer for long-term use due to its more favorable cardiovascular profile 1
   • Regular monitoring for adverse effects is essential with either medication 1

Common Pitfalls and Caveats

• Avoid combining either NSAID with aspirin when possible, as this increases gastrointestinal risk without clear evidence of cardiovascular protection 1
• Do not assume that adding a PPI completely eliminates gastrointestinal risk; it reduces but does not eliminate the risk of complications 1
• Avoid both medications in the perioperative period for coronary artery bypass graft surgery 1
• Be aware that poor compliance with gastroprotective agents can increase the relative risk of NSAID-induced upper GI adverse events 4-6 times 1
• Remember that both medications can affect renal function and blood pressure control, which requires monitoring 1