What anti-inflammatories (Non-Steroidal Anti-Inflammatory Drugs) are associated with arrhythmias?

From the Guidelines

Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 (COX-2) inhibitors are associated with an increased risk of arrhythmias, particularly atrial fibrillation (AF).

Key Findings

• The use of NSAIDs and COX-2 inhibitors increases the risk of AF, particularly in new users, with an incidence rate ratio of 1.33 (1.26–1.41) for non-selective NSAIDs and 1.50 (1.42–1.59) for selective COX-2 inhibitors 1.
• The association is strongest for new users, with a risk increase of 1.46 (1.33–1.62) for non-selective NSAIDs and 1.71 (1.56–1.88) for COX-2 inhibitors 1.
• Celecoxib is not associated with an increased risk of AF 1.

Mechanisms

• NSAIDs may increase the risk of AF through renal and cardiovascular related actions that increase blood pressure and plasma volume, and reduce the antiarrhythmic and anti-inflammatory effects of prostacyclin via a COX-2 inhibition 1.
• The increased risk tends to disappear following NSAID treatment discontinuation 1.

Important Considerations

• The risk of AF is greater at the beginning of NSAID therapy, for short-term use, and in those treated with high doses 1.
• Corticosteroids, particularly oral corticosteroids, may also increase the risk of AF, especially at high doses (≥ 7.5 mg of prednisone equivalents) 1.

From the Research

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Arrhythmias

• The use of NSAIDs has been associated with an increased risk of atrial fibrillation (AF) 2, 3, 4.
• A meta-analysis found that NSAID use was associated with a pooled risk ratio of AF of 1.29 (95% CI 1.19-1.39) compared to non-NSAID users 4.
• Specific NSAIDs, such as ibuprofen, naproxen, and diclofenac, have been found to be associated with an increased risk of AF, with pooled risk ratios of 1.30,1.44, and 1.37, respectively 4.
• Another study found that new NSAID use may predispose patients to AF, and the risk is almost doubled in heart failure patients 3.
• The effects of NSAIDs on ventricular arrhythmias are not well established and would require further investigations 2.

Types of Arrhythmias Associated with NSAIDs

• Atrial fibrillation (AF) is the most common type of arrhythmia associated with NSAID use 2, 3, 4.
• Ventricular arrhythmias have been associated with oral steroids, but the evidence for NSAIDs is limited 5.
• Supraventricular tachycardia has been associated with long-term use of oral steroids and short-term use of theophylline, but the evidence for NSAIDs is limited 5.

Patient Populations at Risk

• Patients with heart failure are at a higher risk of developing AF when using NSAIDs 3.
• Patients with chronic kidney or pulmonary disease may be at a higher risk of developing AF when using selective COX2 inhibitors 3.