What are the risks of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in individuals with vascular disease?

From the Guidelines

NSAIDs should be avoided or used with extreme caution in people with vascular disease due to their significant cardiovascular risks. The use of NSAIDs in individuals with vascular disease is associated with an increased risk of cardiovascular events, including heart attack, stroke, and heart failure exacerbation, as evidenced by a large Danish observational study 1. Common NSAIDs like ibuprofen, diclofenac, and celecoxib have been shown to have a dose-related increase in risk of death and non–dose-dependent trends for rehospitalization for MI 1.

Key Considerations

• The risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk in the patient 1.
• Non-pharmacological approaches are recommended as the first line of treatment, followed by a stepped-care approach to pharmacological therapy.
• If NSAIDs are absolutely necessary, they should be used at the lowest effective dose for the shortest possible duration, with naproxen potentially having a slightly better cardiovascular safety profile than others.
• Regular monitoring of blood pressure, kidney function, and cardiovascular symptoms is essential during NSAID use 1.

Alternative Treatment Options

• Acetaminophen (up to 3000mg daily in divided doses) should be considered as a first-line alternative for patients with vascular disease who require pain management.
• Other alternatives, such as nonacetylated salicylates, tramadol, or small doses of narcotics, may also be considered 1.

Safety Precautions

• NSAIDs should not be combined with anticoagulants or antiplatelet drugs without careful medical supervision due to increased bleeding risks.
• Patients should be educated about warning signs of cardiovascular complications, such as chest pain, shortness of breath, or neurological symptoms, that warrant immediate medical attention.

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 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 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.

Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see CONTRAINDICATIONS]

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

The risks of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in individuals with vascular disease include:

• Increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal
• Higher absolute incidence of excess serious CV thrombotic events in patients with known CV disease or risk factors
• Increased risk of reinfarction, CV-related death, and all-cause mortality in the post-MI period
• Contraindication in the setting of CABG surgery due to increased incidence of myocardial infarction and stroke 2

From the Research

Risks of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Individuals with Vascular Disease

• The use of NSAIDs is associated with an increased risk of adverse cardiovascular events, including myocardial infarction, heart failure, and cerebrovascular events 3, 4, 5, 6, 7.
• Selective cyclooxygenase 2 (COX2) inhibitors have been associated with the greatest risk of adverse vascular effects, but non-selective NSAIDs, especially those with strong COX2 inhibition such as diclofenac, also pose a concern 3, 4, 6.
• The risk of adverse cardiovascular events is heterogenous across NSAIDs, with naproxen and low-dose ibuprofen appearing to have a lower increased cardiovascular risk among NSAIDs 4.
• Factors that influence the cardiovascular risk associated with NSAID use include NSAID class, COX-2 selectivity, treatment dose and duration, and baseline patient risk 4, 5.
• NSAID use is discouraged in patients with cardiovascular disease, but pain-relief medication is often required, and NSAIDs are frequently prescribed due to the lack of safer alternatives 3, 6.
• The use of NSAIDs can interact with many drugs used in patients with cardio- or cerebrovascular disorders, leading to uncontrolled hypertension, aggravation of heart failure, and increased bleeding risk 6.

Cardiovascular Risks Associated with NSAID Use

• Increased risk of myocardial infarction and strokes, particularly with COX-2 inhibitors 4, 6.
• Increased risk of heart failure, especially with non-selective NSAIDs 3, 5.
• Increased risk of cerebrovascular events, including ischemic and hemorrhagic strokes 4, 7.
• Dose-related response in risk associated with NSAID therapy, supporting a causal association 5.

Recommendations for NSAID Use in Patients with Vascular Disease

• NSAIDs should be avoided in patients with cardio- or cerebrovascular disorders, and alternative pharmaceutical, physical, or surgical therapy should be applied 6.
• If NSAIDs are inevitable, their side effects should be well monitored, and they should be prescribed with caution when given in combination with other medications 6.
• COX-2 inhibitors should be avoided in patients with known coronary or cerebrovascular disorders 6.
• Naproxen and low-dose ibuprofen may have a lower cardiovascular risk profile, but any NSAID can be optimized if used at the lowest effective dose for the shortest amount of time, especially among individuals with increased cardiovascular risk 4.