Why are nonsteroidal anti-inflammatory drugs (NSAIDs) contraindicated in coronary artery disease (CAD)?

From the Guidelines

NSAIDs are contraindicated in coronary artery disease (CAD) due to their significant cardiovascular risks, including increased risk of heart attack, stroke, heart failure exacerbation, and death, as evidenced by studies such as 1.

Key Points to Consider

• The use of NSAIDs in CAD patients can disrupt the balance between prothrombotic thromboxane and protective prostacyclin, leading to increased blood pressure, endothelial dysfunction, and enhanced thrombotic potential 1.
• NSAIDs can also reduce the effectiveness of several cardiac medications, particularly aspirin, ACE inhibitors, and diuretics, further compromising cardiovascular health 1.
• For CAD patients requiring pain management, acetaminophen (Tylenol) is generally the safest first-line option, with dosing not exceeding 3,000 mg daily 1.
• If stronger pain control is needed, consultation with a cardiologist is recommended to determine the safest approach, which might include limited, low-dose NSAID use for the shortest duration possible, or alternative pain management strategies such as topical analgesics or physical therapy 1.

Evidence-Based Recommendations

• The 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes recommends that NSAIDs with increasing degrees of relative COX-2 selectivity should not be administered to patients with NSTE-ACS and chronic musculoskeletal discomfort when therapy with acetaminophen, nonacetylated salicylates, tramadol, small doses of narcotics, or nonselective NSAIDs provide acceptable pain relief 1.
• The guideline also states that selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk, and the risk appears to be amplified in patients with established cardiovascular disease 1.

From the FDA Drug Label

WARNINGS CARDIOVASCULAR EFFECTS 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 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. Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment Avoid the use of ibuprofen tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events.

NSAIDs are contraindicated in CAD because they increase the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. Patients with known coronary artery disease (CAD) or risk factors have a higher absolute incidence of excess serious CV thrombotic events due to their increased baseline rate.

• The use of NSAIDs in patients with a recent myocardial infarction (MI) should be avoided unless the benefits outweigh the risk of recurrent CV thrombotic events 2.
• The risk of CV thrombotic events with NSAID use is similar in patients with and without known CV disease, but those with known CV disease have a higher absolute risk due to their increased baseline rate 2.
• Key points:
  • Increased risk of CV thrombotic events with NSAID use
  • Higher absolute risk in patients with known CV disease or risk factors
  • Avoid NSAID use in patients with recent MI unless benefits outweigh risks
  • Monitor patients for signs of cardiac ischemia if NSAIDs are used in patients with CAD 3.

From the Research

NSAIDs Contraindication in CAD

NSAIDs are contraindicated in coronary artery disease (CAD) due to the increased risk of cardiovascular events. The evidence suggests that:

• NSAIDs, particularly diclofenac, ibuprofen, and higher doses of celecoxib and rofecoxib, increase the risk of serious coronary heart disease and cardiovascular disease/death in patients with CAD 4.
• The use of NSAIDs in patients with non-obstructive CAD is associated with an increased risk of major adverse cardiac events, including myocardial infarction, coronary intervention, and death 5.
• The risk of cardiovascular disease attributed to non-aspirin NSAIDs is a concern, and healthcare providers should consider the benefits and risks of these drugs when deciding whether to prescribe them 6.
• The literature review suggests that NSAIDs are associated with a significant increase in the risk of cardiovascular events, both fatal and nonfatal, and that alternative options for pain treatment should be considered 7.

Specific NSAIDs and CAD Risk

The risk of CAD associated with specific NSAIDs is:

• Naproxen: considered to have better cardiovascular safety compared to diclofenac, ibuprofen, and higher doses of celecoxib and rofecoxib 4.
• Diclofenac: associated with an increased risk of serious coronary heart disease and cardiovascular disease/death in patients with CAD 4, 5.
• Ibuprofen: associated with an increased risk of serious coronary heart disease and cardiovascular disease/death in patients with CAD 4, 5.
• Celecoxib: higher doses associated with an increased risk of serious coronary heart disease and cardiovascular disease/death in patients with CAD 4.
• Rofecoxib: associated with an increased risk of serious coronary heart disease and cardiovascular disease/death in patients with CAD 4.

Clinical Implications

The clinical implications of NSAID use in CAD patients are:

• Healthcare providers should carefully consider the benefits and risks of NSAIDs when deciding whether to prescribe them for pain relief in patients with CAD 6.
• Alternative options for pain treatment, such as analgesic drugs with different mechanisms of action, should be considered 7.
• Anti-inflammatory therapy may reduce the incidence of cardiovascular events in patients with CAD, but increases the risk of infection 8.