Paper Symposium
Activity Date: June 2003  — Activity Info: Volume 3, (6B)
Goals & Objectives | Faculty | Introduction | Full Activity Content | CME Test & Evaluation (CME Expired) | Order Copy of Activity


This issue of Advanced Studies in Medicine presents highlights from a series of symposia on the prevention of adverse gastrointestinal (GI) events related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The series, which was accredited for continuing medical education by the Johns Hopkins University School of Medicine, was specifically developed to address the concerns of decision makers in managed care organizations.

The clinician interview, 4 case studies, and abstracts of 6 recently published articles included in this issue bring the clinical and economic impact of NSAID-related GI events into focus and suggest strategies to prevent these events. These 3 editorial formats encompass many of the issues involved in choosing NSAID therapy and preventing GI events, which include the following:

  • The need to recognize NSAID-related GI events as a serious and common medical problem;
  • The need to recognize that many adverse GI events related to aspirin and NSAID use can be prevented;
  • The need to identify patient risk factors for NSAID-related GI events;
  • The impact of aspirin on NSAID-related GI events and its critical role in choosing regimens to prevent their occurrence; and
  • The impact of gastroprotective agents on decreasing GI toxicity in chronic NSAID users.

NSAID Use and GI Complications
An estimated 13 million Americans, or 5.4% of the population, take an NSAID on a regular basis.1 Among those older than 65 years of age, 79% take NSAIDs weekly, and 34% take at least 1 tablet daily.2 However, NSAIDs have long been associated with adverse GI complications. Recent reports indicate that NSAID-related complications account for more than 100 000 hospitalizations and an estimated 16 500 deaths annually, making these complications the 15th most common cause of death in the United States.3

Prevention Strategies
The first strategy for preventing NSAID-related GI events is to know which factors increase the risk for these events and to assess each patient accordingly. Risk is generally greatest within the first month of NSAID use; however, complications beyond this initial period are common. What is often forgotten is the increased risk in those patients who require aspirin for cardioprotection in addition to NSAIDs for relief of pain and inflammation. This underappreciated risk factor has been referred to as a prime example of "when two rights make a wrong."

Although a history of ulcer complications is a strong risk factor for future NSAID-related complications, most patients who develop GI complications have no previous symptoms.3,4 It is therefore crucial to consider prevention of GI complications in patients taking NSAIDs before symptoms develop.

Other preventive strategies include discontinuation of NSAIDs or use of non-NSAID analgesics, decreasing the NSAID dose, switching from a traditional NSAID to a cyclooxygenase-2 (COX-2) selective inhibitor, prescribing misoprostol to protect the GI tract, and prescribing antisecretory therapy with agents such as H2-receptor antagonists or proton pump inhibitors (PPIs).

In This Publication
The clinician interview featured in this issue of Advanced Studies in Medicine addresses several of the clinical and economic issues involved in preventing NSAID-related GI events. It emphasizes a strategy to stratify patients on the basis of GI risk and the need for aspirin prophylaxis (based on cardiovascular risk) and to choose NSAID therapy and concomitant GI therapy accordingly (Figure).5

The 4 case studies illustrate the use of the 2 x 2 matrix in the clinical setting, with each case focusing on a different quadrant of risk with the matrix.

The 6 abstracts chosen for inclusion in this publication add to the body of evidence in favor of using safer NSAIDs (ie, the COX-2 selective inhibitors) and concomitant therapy to prevent NSAID-related GI events. The first abstract is devoted to the 2 x 2 matrix; the second compares the efficacy of 2 gastroprotective agents for ulcer prevention in long-term NSAID users; the third reviews the major controversies in COX-2 selective inhibition; the fourth compares a COX-2 inhibitor with a traditional NSAID plus a PPI; the fifth evaluates the efficacy of a PPI in the prevention of ulcer complications in patients using long-term low-dose aspirin; and the last describes the complementary roles of COX-2 inhibitors and PPIs.

Rounding out this publication is the continuing education test, which is also available online. We hope you find the material presented herein to be valuable to your health plan.

Figure. A Clinician's Guide to the Selection of NSAID Therapy

No Aspirin Traditional NSAID COX-2 Inhibitor
If on PPI, add traditional NSAID
Aspirin* Traditional NSAID plus gastroprotective agent Gastroprotective agent Irrespective of NSAID used

1. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med. 1999;340:1888-1899.
2. Johnson RE, Hornbrook M, Hooker RS, Woodson GT, Shneidman R. Analysis of the costs of NSAID-associated gastropathy. Experience in a US health maintenance organization. Pharmacoeconomics. 1997;12:76-88.
3. Singh G, Ramey DR, Morfeld D, Shi H, Hatoum HT, Fries JF. Gastrointestinal tract complications of nonsteroidal anti-
inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study. Arch Intern Med. 1996;156:1530-1536.
4. Armstrong CP, Blower AL. Nonsteroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut. 1987;28:527-532.
5. Fendrick AM, Garabedian-Ruffalo SM. A clinicianÕs guide to the selection of NSAID therapy. Pharm Ther. 2002; 27:579-580,582.

*Associate Professor of Medicine and Health Management and Policy, Schools of Medicine and Public Health, University of Michigan, Ann Arbor;  Assistant Professor of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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