From the Guidelines
NSAIDs should be avoided in patients with coronary artery disease (CAD) due to their potential to increase cardiovascular risk. The pathophysiology behind this contraindication lies in the mechanism of action of NSAIDs, which inhibit cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2, disrupting the balance between thromboxane A2 (a vasoconstrictor and platelet aggregator) and prostacyclin (a vasodilator and platelet inhibitor) 1. This imbalance promotes vasoconstriction, platelet aggregation, and thrombus formation, potentially worsening coronary blood flow in already narrowed arteries. Additionally, NSAIDs can cause sodium and water retention, increasing blood pressure and cardiac workload, as evidenced by an average increase of 5 mm Hg in mean blood pressure while taking nonselective NSAIDs 1.
Key points to consider in the management of CAD patients include:
- The potential for NSAIDs to interfere with the cardioprotective effects of aspirin and reduce the effectiveness of certain antihypertensive medications like ACE inhibitors and diuretics
- The increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with NSAID use in patients with unstable angina or non-ST-elevation myocardial infarction, leading to the recommendation to discontinue NSAIDs, except for ASA, in these patients 1
- The importance of using alternative pain management strategies, such as acetaminophen for mild pain, and reserving NSAIDs for only necessary cases, with the lowest effective dose and shortest duration possible
- The potential slightly better cardiovascular safety profile of naproxen compared to other NSAIDs, although this should not outweigh the caution against using NSAIDs in CAD patients
- The necessity for regular monitoring of blood pressure, renal function, and cardiovascular symptoms if NSAIDs must be used in CAD patients.
From the Research
Pathophysiology of Coronary Artery Disease and NSAID Use
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular events, including myocardial infarction, coronary intervention, and death, in patients with coronary artery disease (CAD) 2, 3, 4, 5.
Mechanisms of Increased Cardiovascular Risk
- The exact mechanisms of increased cardiovascular risk are not fully understood, but it is thought that NSAIDs may increase blood pressure, worsen renal function, and promote thrombosis 4, 5.
- The use of NSAIDs can also lead to a decrease in the production of prostacyclin, a prostaglandin that has anti-thrombotic properties, which can further increase the risk of cardiovascular events 2, 5.
- Additionally, some studies have suggested that the use of certain types of NSAIDs, such as cyclooxygenase-2 (COX-2) inhibitors, may be associated with a higher risk of cardiovascular events compared to traditional NSAIDs 3, 5.
Clinical Implications
- The increased risk of cardiovascular events associated with NSAID use in patients with CAD has important clinical implications, and alternative treatments for pain management should be considered in these patients 2, 4, 5.
- The Italian Drug Agency has published a warning on the careful prescription of NSAIDs in patients with overt heart disease, such as coronary artery disease and heart failure 2.
- Other studies have suggested that the use of proton pump inhibitors (PPIs) may be associated with reduced chest pain, emergency department visits, and hospitalizations in patients with CAD 6.
Patient-Specific Factors
- Patient-specific factors, such as age, comorbidities, and baseline cardiovascular risk, should be taken into account when considering the use of NSAIDs in patients with CAD 4, 5.
- The risk of adverse cardiovascular events is heterogenous across NSAIDs, and some NSAIDs, such as naproxen and low-dose ibuprofen, may have a lower increased cardiovascular risk compared to others 5.