Background on NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have a long and storied history, beginning with the use of salicylate-containing willow bark for pain and fever relief in ancient cultures. The active component, salicylic acid, was chemically synthesized in 1860, leading to the development of acetylsalicylic acid (aspirin) in 1897. Aspirin’s success spurred the development of other NSAIDs, which were initially organic acids but later included non-acidic compounds.

NSAIDs exert their effects primarily through the inhibition of cyclooxygenase (COX) enzymes, which are crucial for prostaglandin synthesis. There are two main isoforms: COX-1, which is involved in maintaining physiological functions such as gastrointestinal protection and platelet aggregation, and COX-2, which is induced during inflammation and mediates pain and fever. The discovery of these isoforms in the 1990s led to the development of selective COX-2 inhibitors (coxibs), designed to reduce gastrointestinal side effects associated with non-selective NSAIDs. However, the introduction of coxibs like celecoxib and rofecoxib revealed significant cardiovascular risks, leading to the withdrawal of rofecoxib from the market in 2004. This highlighted the need for a balance between efficacy and safety in NSAID therapy.

NSAIDs have widespread use and therapeutic benefits, but note that they are associated with adverse effects, including gastrointestinal ulcers, cardiovascular events, and renal toxicity. Strategies to mitigate these risks include using the lowest effective dose for the shortest duration and co-prescribing gastroprotective agents like proton-pump inhibitors for high-risk patients. The ongoing evolution of NSAIDs aims to enhance their safety while maintaining their efficacy in treating pain, inflammation, and fever.

Mitigating the Risks for Patients Who Need to use NSAIDs

To monitor and mitigate the risks for patients who need to use NSAIDs, especially those with a history of gastrointestinal (GI) bleeding, cardiovascular disease, or renal impairment, several strategies can be employed:

1. Use the Lowest Effective Dose for the Shortest Duration: This is a fundamental principle to minimize adverse effects. The FDA emphasizes this approach to reduce the risk of GI bleeding, cardiovascular events, and renal toxicity.
2. Gastrointestinal Protection: For patients with a history of GI bleeding or at high risk, co-therapy with proton-pump inhibitors (PPIs) or misoprostol is recommended. The American College of Gastroenterology advises using a COX-2 inhibitor plus a PPI or misoprostol for high-risk patients. Testing and eradicating  pyloriinfection can also reduce the risk of peptic ulcers in NSAID users.
3. Cardiovascular Risk Management: The American Heart Association recommends avoiding NSAIDs, particularly COX-2 inhibitors, in patients with cardiovascular disease. If NSAIDs are necessary, naproxen may be preferred due to its relatively lower cardiovascular risk. Monitoring blood pressure and managing other cardiovascular risk factors are crucial.
4. Renal Function Monitoring: Regular monitoring of renal function, fluid retention, and electrolyte levels is essential, especially in patients with preexisting renal impairment, heart failure, or those on diuretics or ACE inhibitors. The FDA and other literature recommend avoiding NSAIDs in patients with advanced renal disease and using alternative therapies when possible.
5. Patient Education and Monitoring: Educate patients about the signs and symptoms of GI bleeding, cardiovascular events, and renal impairment. Regular follow-up and prompt evaluation of any adverse symptoms are critical.

By implementing these strategies, clinicians can better manage the risks associated with NSAIDs used in vulnerable patient populations.

Patient Groups That Should Avoid NSAIDs

Certain patient groups should avoid using nonsteroidal anti-inflammatory drugs (NSAIDs) due to their potential adverse effects, including gastrointestinal (GI) ulcers, cardiovascular events, and renal toxicity.

• Elderly patients are at increased risk for NSAID-related adverse effects, including GI bleeding, renal impairment, and cardiovascular events. Elderly patients, especially those with comorbidities, are particularly vulnerable to these risks.
• Patients with a history of peptic ulcer disease or gastrointestinal bleeding should avoid NSAIDs due to a significantly increased risk of GI bleeding. The FDA notes that these patients have a greater than 10-fold increased risk for developing a GI bleed when using NSAIDs.
• Patients with cardiovascular disease or patients at high risk for cardiovascular events should avoid NSAIDs, particularly COX-2 inhibitors, due to the increased risk of myocardial infarction and stroke. The American Heart Association advises against the use of NSAIDs in patients with established cardiovascular disease.
• Patients with renal impairment, heart failure, or chronic kidney disease (CKD) should avoid NSAIDs due to the risk of worsening renal function and potential for acute kidney injury. The National Comprehensive Cancer Network (NCCN) guidelines recommend caution in these patients to prevent renal toxicities.
• Patients on concurrent anticoagulant or corticosteroid therapy should avoid NSAIDs due to the increased risk of GI bleeding and other complications. The NCCN guidelines also emphasize the increased bleeding risk when NSAIDs are used with anticoagulants.

List of NSAIDs Available in the United States

The following is a list of commonly available NSAIDs in the United States by generic and brand name: