Does diclofenac (Non-Steroidal Anti-Inflammatory Drug (NSAID)) gel increase cardiovascular (CV) risk?

Cardiovascular Risk of Diclofenac Gel

Topical diclofenac gel has a favorable safety profile with minimal cardiovascular risk compared to oral NSAIDs, making it a preferred first-line pharmacological treatment option for localized pain. 1

Topical vs. Oral Diclofenac: Cardiovascular Risk Profile

• Topical diclofenac gel shows small improvements in pain and function with a significantly better safety profile than oral NSAIDs 1
• Pooled safety data from randomized clinical trials comparing topical diclofenac gel with placebo demonstrated similar low rates of adverse effects in both low-risk and high-risk patients (including those with hypertension, type 2 diabetes, or cerebrovascular/cardiovascular disease) 1
• Topical NSAIDs like diclofenac gel have been specifically developed to avert systemic NSAID-related adverse effects, including cardiovascular risks 1

Cardiovascular Risk of Oral Diclofenac

For context, it's important to understand the cardiovascular risks associated with oral diclofenac:

• Oral diclofenac has a relative risk of 1.63 (95% CI 1.12-2.37) for vascular events compared to placebo, significantly higher than other NSAIDs like naproxen 1
• Oral diclofenac has been associated with a 54% increased risk of recurrent myocardial infarction (RR 1.54,95% CI 1.23-1.93) and 140% increased mortality risk (RR 2.40,95% CI 2.09-2.80) compared to placebo in registry studies 2
• Oral diclofenac lies on the more COX-2 selective end of the spectrum of COX inhibition, explaining its higher thrombotic risk profile similar to selective COX-2 inhibitors 2

Why Topical Diclofenac Has Lower CV Risk

• Topical diclofenac results in significantly lower systemic absorption compared to oral formulations, reducing the degree of COX-2 inhibition and consequently lowering the risk of cardiovascular events 3
• Short-term use (less than 30 days) of even low-dose oral diclofenac carries very low cardiovascular risk, and topical formulations provide even lower systemic exposure 3
• At doses below the maximal daily OTC dose and for durations associated with typical OTC usage, there is no clear association with increased CV risk for topical diclofenac 4

FDA Labeling and Warnings

While the FDA labeling for topical diclofenac includes warnings about cardiovascular risk, these are standard for all NSAIDs:

• The FDA recommends using "the lowest effective dose for the shortest duration possible" to minimize potential cardiovascular risk 5
• Patients with known cardiovascular disease or risk factors should be monitored when using any NSAID product, including topical formulations 5

Clinical Recommendations

• Topical NSAIDs like diclofenac gel are recommended as first-line pharmacological treatment for localized pain due to their favorable safety profile compared with oral analgesics 1
• For patients requiring NSAID therapy who have hypertension or cardiovascular risk factors, topical diclofenac is a safer alternative to oral diclofenac based on cardiovascular risk profiles 2
• When treating multiple joints or widespread pain, systemic pharmacological treatment may be preferred over topical application 1

Monitoring and Precautions

• Although the cardiovascular risk is minimal with topical diclofenac, patients with severe heart failure should still use caution 5
• Monitor blood pressure in patients taking antihypertensive medications, as even minimal systemic absorption could potentially affect blood pressure control 5
• Avoid use of topical diclofenac in patients with recent myocardial infarction unless benefits are expected to outweigh risks 5