Heart Failure: NSAID use has been associated with a nearly 10-fold increase in the risk of clinical decompensation in patients with heart failure (HF)14 and 2-fold risk of HF hospitalization.15 The risks seem higher with COX-2 inhibitors (with the exception of celecoxib), compared with non-selective NSAIDs.3

Atrial Fibrillation: Risks for incident atrial fibrillation (AF) in NSAID use are highest in current users, as well as those who used an NSAID within 30–60 days prior to AF diagnosis, with advanced age and preexisting HF as especially predictive.3 However, the differences between specific NSAIDs, doses, or duration of therapy remain unclear.3

Bleeding Complications

NSAIDs have the potential to cause or contribute to hemorrhagic events in patients with CVD. The risk is increased in patients using NSAID monotherapy and taking concomitant antiplatelet and/or anticoagulant therapies, such as vitamin K antagonists and target-specific oral anticoagulants.3

Use of NSAID monotherapy can increase the risk of upper GI complications (UGIC) 2- to 4-fold.16 Independent risk factors include increasing age, alcohol use, anticoagulants, aspirin, cirrhosis, corticosteroids, male sex, recent or current NSAID use, history of peptic ulcer, and smoking.3 Low-dose ibuprofen is associated with the lowest rate of upper GI bleeding (UGIB).3