What is the relationship between Coronary Artery Disease (CAD) and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

From the Guidelines

Patients with coronary artery disease should avoid NSAIDs whenever possible due to their increased cardiovascular risk, as evidenced by the 2014 AHA/ACC guideline 1. The use of NSAIDs in patients with coronary artery disease is associated with a higher risk of cardiovascular events, including death and rehospitalization for myocardial infarction.

• The risk appears to be amplified in patients with established cardiovascular disease, with a large Danish observational study showing a dose-related increase in risk of death and non–dose-dependent trends for rehospitalization for MI for all NSAIDs 1.
• Selective COX-2 inhibitors, such as rofecoxib and celecoxib, have been associated with a higher risk of cardiovascular events compared to nonselective NSAIDs, with hazard ratios ranging from 2.57 to 2.80 1.
• Non-pharmacological approaches are recommended as the first line of treatment, followed by a stepped-care approach to pharmacological therapy, with acetaminophen being a suitable alternative for pain management 1. When NSAIDs cannot be avoided, it is essential to use the lowest effective dose for the shortest duration possible and to monitor patients closely for signs of cardiovascular adverse effects.
• Naproxen may be considered as an alternative for patients who require NSAID therapy, as it appears to have a lower cardiovascular risk profile compared to other NSAIDs, although the evidence is not as strong as for the harms associated with other NSAIDs 1. Any patient with coronary artery disease experiencing chest pain, shortness of breath, or other concerning symptoms while taking NSAIDs should discontinue use and seek immediate medical attention.

From the FDA Drug Label

Clinical trials of several cyclooxygenase-2 (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 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 However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. In the APC (Adenoma Prevention with Celecoxib) trial, there was about a threefold increased risk of the composite endpoint of cardiovascular death, MI, or stroke for the celecoxib capsules 400 mg twice daily and celecoxib capsules 200 mg twice daily treatment arms compared to placebo The increases in both celecoxib dose groups versus placebo-treated patients were mainly due to an increased incidence of myocardial infarction

Key Points:

• Increased risk of CV thrombotic events: NSAIDs, including celecoxib, increase the risk of serious cardiovascular thrombotic events, such as myocardial infarction and stroke.
• Similar relative risk: The relative increase in CV thrombotic events is similar in patients with and without known CV disease or risk factors.
• Higher absolute risk: Patients with known CV disease or risk factors have a higher absolute incidence of excess CV thrombotic events due to their increased baseline rate.
• Dose-dependent risk: The increase in CV thrombotic risk is most consistently observed at higher doses.

Clinical Decision: Based on the available data, it is recommended to use the lowest effective dose of NSAIDs, including celecoxib, for the shortest duration possible to minimize the potential risk of adverse CV events in patients with coronary artery disease. Physicians and patients should remain alert for the development of CV events throughout the entire treatment course. 2 2 2

From the Research

Coronary Artery Disease and NSAIDs

• The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with coronary artery disease (CAD) is a topic of ongoing debate due to the potential increased risk of adverse cardiovascular events 3, 4, 5, 6, 7.
• Studies have shown that certain NSAIDs, such as naproxen, may have a lower cardiovascular risk profile compared to others, such as diclofenac and ibuprofen 3, 5.
• The risk of adverse cardiovascular events associated with NSAID use is heterogeneous and depends on various factors, including the type of NSAID, dose, duration of use, and baseline patient risk 5, 6.
• Selective COX-2 inhibition, such as with celecoxib, has been shown to improve endothelial function in patients with coronary artery disease, but may also increase the risk of adverse cardiovascular events 4.
• The use of NSAIDs in patients with non-obstructive coronary artery disease has been associated with an increased risk of major adverse cardiac events, including myocardial infarction, coronary intervention, and death 6.
• It is recommended to use NSAIDs at the lowest effective dose for the shortest amount of time, especially in patients with increased cardiovascular risk 5, 7.
• The interference of specific NSAIDs with the established cardiovascular protective role of low-dose aspirin is also a concern and should be taken into account when prescribing NSAIDs to patients with CAD 7.