This proposal addresses the need for outcomes research related to the most commonly prescribed medication in the United States, non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are associated with serious upper gastrointestinal events (UGIE) defined as perforation, obstruction or bleeding. The annual incidence of NSAID-related UGIE is 2.0-4.5%. NSAIDs contribute to 10-20/1000 hospitalizations per year and a 4-fold increased risk of death. At present, the primary strategies for reducing UGIE include: the use of NSAIDs with misoprostol or a proton pump inhibitor, or prescription of a selective Cox-2 inhibiting NSAID (coxib). Current guidelines advocate the use of these strategies in individuals at high risk of UGIE (old age, prior UGIE, concomitant anticoagulant/steroid use or high dose NSAID). However, when we examined national VA provider adherence to recommended guidelines for safe NSAID prescription, we discovered low adherence (27.4 %), even in the presence of multiple risk factors. Furthermore, recent evidence has suggested an increase in NSAID-related cardiovascular morbidity (myocardial infarction and stroke) associated with some of the recommended strategies for safer NSAID prescription. It remains unknown whether this observed low provider adherence is associated with worse patient outcomes. Do these "recommended guidelines" really make a difference? Do current recommended guidelines result in a reduction of GI adverse events and GI healthcare resource utilization? These are the questions we plan to address in this Merit Review Grant.
Specific Aim #1: To determine if provider adherence to recommended NSAID prescription improves GI clinical outcomes among high-risk patients (patients >65 years, patients co-prescribed anticoagulants or steroids, patients on a high average daily dose of NSAID or patients with a prior history of UGIE).
Specific Aim #2: To determine if an adherent strategy using a coxib (versus NSAID with proton pump inhibitor or misoprostol) is associated with a higher risk of cardiovascular events defined as non-fatal acute myocardial infarction and non-hemorrhagic stroke.
Specific Aim #3: To assess the cost-effectiveness of provider adherence to recommended NSAID prescription among high-risk patients. Cost-effectiveness will be assessed by examining the health resource utilization associated with the care of UGIE among patients who had been prescribed a PPI and those who had not been prescribed a PPI.
We performed a retrospective cohort study using medical and pharmacy data from the VA and claims data from a linked dataset of VA and Medicare, spanning the period from 01/01/00-09/30/05. In the first aim, we will use a time-dependent analysis to assess the extent to which provider adherence to clinical guidelines for safe NSAID prescription affects the clinical outcomes of UGIE, NSAID associated GI health resource utilization. In the second aim, we will assess the incidence of NSAID-related myocardial infarction and stroke. In the third aim, we will quantify national health resource cost associated with treatment of NSAID-related UGIE. We will also determine the effect of PPI gastroprotection on hospitalization and resource use to assess the cost-effectiveness of an adherent NSAID prescription strategy versus non-adherent strategy. The descriptive cost-benefit analysis performed will help inform the extent to which the VA would find it in its best interest to pay (willingness to pay) for its providers' adherence to recommended guidelines, should such a practice be associated with superior patient outcomes and lower resource consumption.
The cohort was truncated at the end of 12/31/04, as 2005 Medicare data was not available. Data analysis of all three specific aims has been completed. The results of the specific aims have been presented at national gastroenterology meetings, have received research awards from the American College of Gastroenterology and the American Gastroenterological Association, and presented at the Annual HSR&D meeting. The results of specific aims 1 and 2 have been published as full manuscripts, and the results of specific aim 3 is available in abstract form (citations are available through the ART Website).
Currently, the VA does endorse the use of safer NSAID prescription strategies among high-risk users, but lacks evidence that this adherent strategy results in a reduction of healthcare utilization. Our data is valuable to VA decision makers regarding formulary choices and in shaping prescription policy. We have demonstrated recommended guidelines for gastroprophylaxis of high-risk NSAID users actually reduces UGIE in real-life (Specific Aim #1). We have also demonstrated that the choice of recommended gastroprotection strategy (coxib agent vs. traditional NSAID) has implications on the risk of cardiovascular outcomes such as stroke and heart attack (Specific Aim #2). Finally, we have demonstrated that among high-risk NSAID users who were prescribed a PPI, a significant reduction in hospitalization translates to a meaningful cost-savings for the Department of Veterans Affairs (Specific Aim #3). We believe our analysis will assist VA policy makers in deciding whether or not they should more rigorously embrace current recommended guidelines for the safer prescription of NSAIDs as a national policy.
External Links for this Project
- Cavazos JM, Naik AD, Woofter A, Abraham NS. Barriers to physician adherence to nonsteroidal anti-inflammatory drug guidelines: a qualitative study. Alimentary pharmacology & therapeutics. 2008 Sep 15; 28(6):789-98. [view]
- Abraham NS, El-Serag HB, Hartman C, Richardson P, Deswal A. Cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident. Alimentary pharmacology & therapeutics. 2007 Apr 15; 25(8):913-24. [view]
- Abraham NS, Hartman C, Castillo D, Richardson P, Smalley W. Effectiveness of national provider prescription of PPI gastroprotection among elderly NSAID users. The American journal of gastroenterology. 2008 Feb 1; 103(2):323-32. [view]
- Abraham NS, Castillo DL, Hartman C. National mortality following upper gastrointestinal or cardiovascular events in older veterans with recent nonsteroidal anti-inflammatory drug use. Alimentary pharmacology & therapeutics. 2008 Jul 1; 28(1):97-106. [view]
- Abraham NS, Hartman C, Hasche J. Reduced hospitalization cost for upper gastrointestinal events that occur among elderly veterans who are gastroprotected. Clinical Gastroenterology and Hepatology. 2010 Apr 1; 8(4):350-6; quiz e45. [view]
- Dries AM, Richardson P, Cavazos J, Abraham NS. Therapeutic intent of proton pump inhibitor prescription among elderly nonsteroidal anti-inflammatory drug users. Alimentary pharmacology & therapeutics. 2009 Sep 15; 30(6):652-61. [view]
- Gaspard P, Castillo L, Abraham S. Clinical knowledge gaps, formative training and safer NSAID prescription. Presented at: Digestive Disease Week Annual Meeting; 2008 May 21; San Diego, CA. [view]
- Ramsey J, Richardson, Abraham S. Complex antithrombotic therapy prescription: Prevalence and provider recognition of gastrointestinal risks. Presented at: Digestive Disease Week Annual Meeting; 2008 May 21; San Diego, CA. [view]
- Abraham S, Hasche, Hartman. Cost-benefit of PPI gastroprotection among elderly NSAID users. Presented at: American College of Gastroenterology Annual Meeting; 2007 Oct 16; Philadelphia, PA. [view]
- Desai V, Fitton P, Castillo L, Abraham S. Meta-analysis: Risk of upper gastrointestinal event with over-the-counter non-steroidal anti-inflammatory drugs. Presented at: Digestive Disease Week Annual Meeting; 2008 May 21; San Diego, CA. [view]
- Abraham S, Hartman, Smalley. Mortality following NSAID-related gastrointestinal or cardiovascular event. Presented at: Digestive Disease Week Annual Meeting; 2007 May 23; Washington, DC. [view]
- Abraham S, Castillo L, Naik D. NSAID-cardioprotective drug polypharmacy: Patient beliefs and expectations of treatment goals. Presented at: American Geriatrics Society Annual Meeting; 2008 May 1; Washington, DC. [view]
- Abraham S. NSAIDs in the elderly: Outcomes and implications for medication decision-making. Paper presented at: Northwestern University Feinberg School of Medicine Visiting Professor; 2007 Aug 7; Chicago, IL. [view]
- Abraham S, Hartman, El-Serag, Richardson, Smalley. Outcomes of provider adherence to NSAID prescription guidelines. Presented at: American College of Gastroenterology Annual Meeting; 2006 Oct 23; Las Vegas, NV. [view]
- Abraham NS. The degree of COX-2 selectivity and the risk of cardio and cerebrovascular events. Paper presented at: Digestive Disease Week Annual Conference; 2006 May 22; Los Angeles, CA. [view]
- Abraham NS. Upper Gastrointestinal Bleeding. Paper presented at: Digestive Disease Week Annual Meet the Professor Luncheon; 2007 May 23; Washington, DC. [view]
Treatment - Observational
Behavior (provider), Clinical practice guidelines, Cost effectiveness