What is the potential risk of stroke or other cardiovascular events with oral Diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) compared to other NSAIDs?

From the Guidelines

Diclofenac carries a higher risk of stroke and cardiovascular events compared to most other NSAIDs, with a risk similar to that of COX-2 inhibitors like celecoxib, and should be used with caution in patients with pre-existing cardiovascular disease or risk factors. The cardiovascular risk with diclofenac is due to its COX-2 selectivity, which reduces production of vasodilatory and antithrombotic prostacyclin while maintaining production of prothrombotic thromboxane A2 1. According to a study by Gislason et al., the hazard ratio (HR) for death associated with diclofenac use was 2.40 (2.09 to 2.80), which is higher than that of ibuprofen (1.50,1.36 to 1.67) and other NSAIDs (1.29,1.16 to 1.43) 1.

Key Points to Consider

• The increased cardiovascular risk with diclofenac becomes evident within the first weeks of treatment and increases with higher doses and longer duration of use 1.
• Naproxen appears to have the most favorable cardiovascular risk profile among commonly used NSAIDs, while ibuprofen has an intermediate risk 1.
• For patients with pre-existing cardiovascular disease or risk factors, naproxen would be a safer alternative to diclofenac.
• If NSAID therapy is necessary in high-risk patients, using the lowest effective dose for the shortest duration possible is recommended 1.
• All patients on long-term NSAID therapy should be monitored for cardiovascular complications, especially those with hypertension, diabetes, or other cardiovascular risk factors 1.

Recommendations for Clinical Practice

• Use diclofenac with caution in patients with pre-existing cardiovascular disease or risk factors, and consider alternative NSAIDs with a more favorable cardiovascular risk profile, such as naproxen.
• Monitor patients on long-term NSAID therapy for cardiovascular complications, and adjust treatment accordingly.
• Use the lowest effective dose of NSAIDs for the shortest duration possible to minimize cardiovascular risk.

From the FDA Drug Label

WARNINGS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease.

The potential risk of stroke or other cardiovascular events with oral Diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) compared to other NSAIDs is unclear, as the available data does not show a consistent risk among all NSAIDs 2.

• The relative increase in serious CV thrombotic events is similar for all NSAIDs.
• Patients with known CV disease or risk factors have a higher absolute incidence of excess serious CV thrombotic events.
• The increase in CV thrombotic risk has been observed most consistently at higher doses.
• To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible 2.

From the Research

Comparison of Oral Diclofenac with Other NSAIDs

The potential risk of stroke or other cardiovascular events with oral Diclofenac (Nonsteroidal Anti-Inflammatory Drug (NSAID)) compared to other NSAIDs is as follows:

• Diclofenac has been found to have a higher risk of stroke, myocardial infarction (MI), and major bleeding compared to other NSAIDs such as naproxen and ibuprofen 3, 4, 5, 6.
• Naproxen has been associated with the smallest risk increase for cardiovascular events among NSAIDs 4, 5.
• A study found that diclofenac users had an increased risk of serious coronary heart disease and serious cardiovascular disease/death compared to naproxen users 5.
• Another study found that diclofenac increased the risk of ischemic stroke, particularly when used at high doses, over long-term periods, and in patients with a high background cardiovascular risk 6.
• In contrast, ibuprofen and naproxen did not increase the risk of ischemic stroke 6.
• A retrospective cohort study found that rofecoxib, valdecoxib, and indomethacin were associated with an increased risk of cardiovascular events, while naproxen was associated with a decreased event rate in patients with a history of cardiovascular disease 7.

Key Findings

• Diclofenac has a higher risk of cardiovascular events compared to other NSAIDs.
• Naproxen has a better cardiovascular safety profile compared to diclofenac and other NSAIDs.
• The risk of cardiovascular events with NSAIDs can be influenced by factors such as dose, duration of treatment, and background cardiovascular risk.
• Concomitant use of aspirin does not appear to modify the risk of cardiovascular events with NSAIDs 6.