NSAIDs and Atherosclerotic Cardiovascular Disease

Coronary Artery Disease (CAD): The “totality of evidence” suggests that NSAIDs increase the risks of major adverse cardiovascular events (MACEs) in patients with and without CAD.5 For example, analysis of data from a registry of more than 58,000 patients with prior myocardial infarction (MI) found that use of any NSAID was associated in increased risk of mortality and recurrent MI.5 Moreover, shorter durations of use have not been shown to attenuate the risks associated with NSAIDs in patients with CAD.6

Stroke: Several studies have demonstrated an increased risk of stroke in patients with cerebrovascular disease.7,8,9 While NSAIDs, carry a risk of both hemorrhagic and ischemic stroke, the risk of ischemic stroke is much higher.9 NSAIDs may also decrease the effectiveness of diuretics and increase the risk of renal failure when used in conjunction with angiotensin-converting enzyme (ACE) inhibitors.3

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Blood Pressure: NSAID use has been observed to raise blood pressure (BP) in both normotensive and hypertensive individuals, including those with previously well-controlled hypertension.3 Advanced age and pre-existing hypertension increase the risk of NSAID-induced elevations in blood pressure.3 Elevations in BP do not seem dose-related or associated with duration of use.3

Interaction between NSAIDs and Aspirin: NSAIDs may have a deleterious effect in patients with atherosclerotic CVD by attenuating the antiplatelet effects of aspirin via steric hindrance of the aspirin-binding site on platelet COX-1.3 Several studies have demonstrated the negative interaction of NSAIDs and aspirin in increasing all-cause and cardiovascular mortality, compared with aspirin alone.10,11 However timing of NSAID and aspirin administration can have an impact on risk. For example, when administered two hours prior to aspirin, ibuprofen appears to attenuate the antiplatelet effects of aspirin, while these are preserved if aspirin is administered two hours prior to ibuprofen.12 Naproxen seems to interact with aspirin when administered once, but not twice daily.13