Gastroprophylaxis-indications and Cost-effectiveness

February 13, 2009

Two recent experiences inspired me to bring up the topic of gastroprophylaxis.

Clinical Scenarios:

• 56-year-old male with h/o CAD s/p stent on ASA/plavix

• 46-year-old female with h/o DVT on Coumadin and chronic knee arthritis on ibuprofen

• 72-year-old male with h/o COPD on chronic prednisone and ASA 81mg for primary cardioprophylaxis

• 65-year-old male with h/o Lung CA on chemotherapy and h/o DVT on Coumadin

• 83-year-old male with h/o GERD and CVA on plavix

• 76-year-old female with CAD on ASA and pulmonary embolism on Coumadin

Two recent experiences inspired me to bring up the topic of gastroprophylaxis. First, in the past two weeks, I have taken care of at least one patient who fits each of the above scenarios. Second, I received a letter from a local pharmacy essentially informing me that I may be over-prescribing proton pump inhibitors on my patients. Aware of the well-known concerns that PPIs are often overused without clear indication and thus, may not be cost-effective, I reviewed the above-mentioned scenarios with a few colleagues to hear their thoughts on whether these patients should be discharged on GI prophylaxis. To my surprise, many stated that they would not routinely prescribe medications such as PPIs for their patients with similar medical profiles as above. So I began my literature search for any studies/trials, reviews, or evidence-based guidelines that could shed some light onto this matter.

To my surprise, I could not find many studies or review articles focusing on when gastroprophylaxis is appropriate in the non-ICU setting. I did come across articles that focused on more specific scenarios such as “Treatment and Prevention on NSAID Induced Ulcers,” “Reducing the Risks of Gastrointestinal Bleeding with Antiplatelet Therapies,” “Clopidogrel versus Aspirin and Esomeprazole to Prevent Recurrent Ulcer Bleeding.” Given the lack of large randomized-controlled studies on this topic, it is no surprise that there are no evidence-based guidelines specifying indications for gastroprophylaxis. In these situations where there is no clear evidence to guide our clinical decision making, we often turn to experts to enlighten and guide us.

I would like to thank one of my gastroenterology colleagues (Tara), who referred me to the “ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risk of Antiplatelet Therapy and NSAID Use.” Once again, I want to emphasize that there are no well developed evidence based guidelines that are formally adopted into ACC/AHA practice guidelines; what we have for this topic are expert consensus documents, which serve to inform and guide us in clinical practice while new evidence evolves and is eventually formalized. So with this clarification in mind, I would like to provide an overview of the recommendations provided in this paper. I encourage you to browse the document itself, as it is very informative in that it not only provides the background pathophysiology pertaining to ulcer formation and healing, but also provides references to many well accepted large RCT studies from which the data/recommendations are extrapolated.

Recommendations are summarized as below:

1) GI complications of ASA and non-ASA NSAIDs: As the use of any NSAID, including COX-2-selective agents and OTC doses of traditional NSAIDs, in conjunction with cardiac doses of ASA (325mg and lower), substantially increases the risk of ulcer complications, a gastroprotective therapy should be prescribed for at-risk patients.

2) GI Effects of ASA: The use of low-dose ASA (325mg or less) for cardioprophylaxis is associated with a 2- to 4-fold increase in UGIE (Upper GastroIntestinal Events) risk. Enteric-coated or buffered preparations do not reduce the risk of bleeding. For patients at risk of adverse events, gastroprotection should be prescribed. The risk of UGIE increases with ASA dose escalation; thus for the chronic phase of therapy (outside of ACS), doses greater than 81mg should not be routinely prescribed.

3) GI Effects of Combined ASA and Anticoagulant Therapy: The combination of ASA and anticoagulant therapy (including unfractionated heparin, low molecular-weight heparin, and warfarin) is associated with a clinically meaningful and significantly increased risk of major extracranial bleeding events, a large proportion from the upper GI tract. This combination should be used with established vascular, arrhythmic, or valvular indication; patients should receive concomitant PPIs as well. When Warfarin is added to ASA plus clopidogrel, an international normalized ratio (INR) of 2.0-2.5 is recommended.

4) GI Effects of Clopidogrel: Substitution of clopidogrel for ASA is not a recommended strategy to reduce risk of recurrent ulcer bleeding in high risk patients and is inferior to the combination of ASA plus PPI.

5) GI Effects of Combined Clopidogrel and Anticoagulant Therapy: The combination of clopidogrel and warfarin therapy is associated with an increased incidence of major bleeding when compared with monotherapy alone. Use of combination antiplatelet and anticoagulant therapy should be considered only in cases which the benefits are likely to outweight the risks. When warfarin is added to ASA plus clopidogrel, an INR of 2.0-2.5 is recommended.

6) Treatement and Prevention of ASA and NSAID related Gastroduodenal Injury: PPIs are the preferred agents for the therapy and propylaxis of NSAID and ASA associated GI injury.

7) Role of H. pylori: Testing for and eradicating H. pylori in patients with a history of ulcer disease is recommended before starting chronic antiplatelet therapy.

There is also a relatively self-explanatory algorithm that summarizes their recommendations. Two things to note: first, while the initial starting point is “Need for Antiplatelet Therapy”, the data suggests that this can be replaced with any NSAID; second, the dose of aspirin includes “baby ASA” (81mg). Below is my simple interpretation.

Need for Antiplatelet Therapy (or NSAID)

Assess GI Risk Factors

History of Ulcer (including non-bleeding)

→ Test for H.pylori and treat if infected

History of GI bleeding

Dual Antiplatelet Therapy

Concomitant Anticoagulant Therapy

Age 60 years or more

Corticosteroid Use

Dyspepsia or GERD symptoms

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PPI

Although, the recommendations specify PPIs as the preferred agents for prophylaxis, I have not further investigated if there are studies directly comparing the different classes of medications to conclude which are the most effective in gastroprotection.

From the above 6 scenarios, 3 patients were admitted to my service for work up of GI bleeding in the matter of two weeks. I believe the saying goes, “when it rains, it pours!” For me, this was an opportunity to review this topic and hopefully I have succeeded in heightening awareness in my readers on this topic of gastroprotection. As always, practicing medicine is an art and should be individualized to each patient.

Visit the online version: http://circ.ahajournals.org/cgi/content/full/118/18/1984