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An Overview of Pain Management: The Clinical Efficacy and Value of Treatment
Srinivas Nalamachu, MD
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Quantifying the Impact of NSAID-Associated Adverse Events
Michael Fine, MD

Quantifying the Impact of NSAID-Associated Adverse Events

Michael Fine, MD
Although the FDA warns against long-term use of NSAIDs, several studies have found that the increased risk for GI-, CV-, and renal-related complications is present even when NSAID use is relatively short in duration.7,24,25 As shown in Table 1,7,24,25 the risk increases within the first few weeks of treatment and persists during the course of NSAID therapy. These data suggest that safety and tolerability risks of short-term NSAID therapy should not be overlooked by clinicians.

In addition, as outlined above, studies illustrate that GI, CV, and renal adverse events associated with NSAID use are dose-dependent. It also important to note that dosing used in many of these trials reflect NSAID use that is common to clinical practice; in other words, everyday use of NSAIDs carries notable risk.

Strategies for Reducing the NSAID-Related Burden

Various strategies have been employed to help mitigate the risk for adverse events (Table 2).1,7,26-28 COX-2 inhibitors were initially developed as a safer alternative to traditional NSAIDs. However, data soon emerged that linked their use to an elevated risk for CV-related adverse events. Another strategy involves the addition of an enteric coating, which is often used on aspirin and ibuprofen to help alleviate stomach irritation.

Another option used by some clinicians is to add a gastroprotective agent to the NSAID regimen. This approach has shown some reduction in GI events. However, a pharmacoeconomic study comparing the cost of GI adverse events in patients taking NSAIDs (n = 10,540) with those taking NSAIDs plus the gastroprotective agent misoprostol (n = 1533) found that the groups had statistically similar rates of GI-related hospitalizations, GI-related healthcare resource utilization, and costs associated with these resources over the 2-year period.29 Additionally, none of these strategies address the risk for CV or renal complications.

Over the past decade, data have shown that the risk for adverse events is strongly associated with baseline risk, NSAID dosage, and duration of use. It is up to the clinician to carefully weigh the risk and benefits for each patient based on his or her pain symptoms and baseline risk for GI, CV, or renal complications. While individual risk factors are an important consideration, another key strategy to reduce risk for all patients is for clinicians to prescribe the lowest effective dose for the shortest possible duration, as recommended by the FDA and numerous other regulatory bodies and medical organizations.30

Conclusion

NSAIDs remain a viable choice among clinicians and patients for the treatment of a variety of painful conditions. Efforts to mitigate the common GI-related adverse events have had mixed results, and have failed to address the added risk for serious CV and renal complications. Moreover, several studies comparing the safety of traditional NSAIDs with the newer COX-2 inhibitors on the market have shown that the RR varies, and that neither drug class has a clear safety advantage. The available data suggest that NSAID-related adverse events place a substantial clinical and economic burden on the healthcare system. Finding the lowest effective dose and shortest duration of treatment that still provides sufficient clinical efficacy should be the goal for physicians who are managing their patients’ pain with NSAIDs.

Author affiliation: Health Net, Laguna Beach, California.
Funding source: This supplement was sponsored by Iroko Pharmaceuticals, LLC.
Author disclosure: Dr Fine reports no significant financial relationships with commmercial interests.
Authorship information: Concept and design; analysis and interpretation of data; drafting of the manuscript; and critical revision of the manuscript for important intellectual content.
Address correspondence to: Michael Fine, MD, Medical Director, Health Net, 736 Kendall Dr, Laguna Beach, CA 92651. E-mail: mfine49@icloud.com.
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