Apply patient risk factors to visualize the ACG/AGA NSAID safety profile.
Guidelines & Evidence
Clinical Details
Section 1
When to Use
When to Use
Selecting the safest NSAID or COX-2 inhibitor regimen for patients requiring long-term anti-inflammatory therapy
To identify patients who require co-therapy with a Proton Pump Inhibitor (PPI) or Misoprostol
Evaluating the risk of upper GI bleeding, perforation, or obstruction (PUPO)
The "GI vs. CV" Balance
Clinical decision-making for NSAIDs must balance GI risk against Cardiovascular (CV) risk. A patient with high GI risk but high CV risk should generally avoid both traditional NSAIDs and COX-2 inhibitors.
Section 2
Formula & Logic
High-Risk Features
History of prior complicated ulcer (Perforation/Obstruction/Bleeding).
Age > 65 years.
Concomitant Use of: anticoagulants (warfarin/DOAC), anti-platelets (aspirin/clopidogrel), or oral corticosteroids.
Multiple NSAID use (including low-dose aspirin).
High-dose NSAID therapy.
Concomitant H. pylori infection.
Risk Stratification (ACG 2009)
High Risk
Prior complicated ulcer OR > 2 risk factors
Moderate Risk
1–2 risk factors
Low Risk
No risk factors
Section 3
Pearls/Pitfalls
COX-2 Inhibitors and the Gut
Celecoxib (COX-2 selective) significantly reduces the risk of macroscopic GI ulcers compared to traditional NSAIDs (like naproxen or ibuprofen). However, when Celecoxib is combined with low-dose Aspirin, its GI safety advantage is nearly completely lost.
Naproxen — The Cardiovascular Paradox
Naproxen is generally considered the "safest" NSAID for patients with high cardiovascular risk (lowest risk of MACE), but it is associated with a higher risk of GI bleeding compared to Ibuprofen or Celecoxib. For these patients, Naproxen + PPI is often the preferred strategy.
Clinical Pearls
Co-prescription of a PPI reduces the risk of symptomatic NSAID-ulcers by > 70%
Misoprostol is also highly effective but limited by GI side effects (dose-dependent diarrhea)
The risk of a GI event is highest during the first month of NSAID initiation
Section 4
Next Steps
Management Recommendations (ACG)
Low Risk
Traditional NSAID at lowest effective dose
Moderate Risk
NSAID + PPI (or Misoprostol) OR COX-2 inhibitor alone
High Risk
COX-2 inhibitor + PPI OR alternative therapy (e.g., Acetaminophen/Opioids)
Complementary Tools
HAS-BLED Score (Bleeding Risk)
H. pylori Eradication Algorithm
Peptic Ulcer Re-bleed Risk (Forrest)
Section 5
Evidence Appraisal
ACG Clinical Guideline
Guidelines for prevention of NSAID-related ulcer complications.
Lanza FL et al. • American Journal of Gastroenterology. 2009;104(3):728-38. The definitive evidence-based roadmap.
The American College of Gastroenterology convened this panel to address the "hidden epidemic" of NSAID gastropathy, which was responsible for over 100,000 hospitalizations in the US annually before the widespread use of PPIs.
