Do Clopidogrel (Plavix) and Apixaban (Eliquis) increase the risk for peptic ulcer disease?

From the Guidelines

Both clopidogrel (Plavix) and apixaban (Eliquis) can increase the risk of peptic ulcers, though they do so through different mechanisms and to different degrees. Clopidogrel carries a moderate risk of peptic ulcer development because it inhibits platelet aggregation, which can impair the normal healing process of the gastric mucosa and potentially lead to ulcer formation or bleeding 1. The combined use of clopidogrel and nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, has been associated with impaired healing of asymptomatic ulcers and with an increase in serious upper GI bleeding 1.

Key Points to Consider

• The risk of peptic ulcers is significantly higher when these medications are combined with other risk factors such as concurrent NSAID use, H. pylori infection, advanced age, or a history of previous ulcers 1.
• Patients taking either medication, especially clopidogrel, may benefit from preventive measures such as proton pump inhibitors (like omeprazole 20mg daily) to reduce gastric acid production and protect the stomach lining 1.
• It's essential for patients to promptly report any symptoms of ulcers such as persistent stomach pain, black stools, or vomiting blood to their healthcare provider, as these could indicate serious complications requiring immediate attention.
• The use of PPIs has been shown to decrease the risk of gastroduodenal ulcers and upper GI bleeding in patients taking aspirin or NSAIDs, and also decreases the risk of GI bleeding associated with the combination of clopidogrel and aspirin 1.

Recommendations for Patients

• Patients should be closely monitored for signs of peptic ulcers, especially when taking clopidogrel or apixaban in combination with other medications that increase the risk of ulcers.
• The use of proton pump inhibitors should be considered for patients at high risk of peptic ulcers, especially those taking clopidogrel or apixaban 1.
• Patients should be educated on the importance of reporting any symptoms of ulcers promptly to their healthcare provider.

From the FDA Drug Label

CONTRAINDICATIONS Active pathological bleeding, such as peptic ulcer or intracranial hemorrhage (4.1) Bleeding: Clopidogrel increases risk of bleeding. (5. 2) Nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs, SNRIs): Increases risk of bleeding. ( 7.4,7.5,7.6)

The FDA drug label for Clopidogrel indicates that it increases the risk of bleeding, including bleeding related to peptic ulcer disease 2. However, there is no information provided about Apixaban (Eliquis) in the given drug labels.

• Key points:
  • Clopidogrel increases the risk of bleeding.
  • Active pathological bleeding, such as peptic ulcer, is a contraindication for Clopidogrel.
  • No information is available about Apixaban (Eliquis) in the provided drug labels.

From the Research

Clopidogrel and Peptic Ulcer Disease

• Clopidogrel causes significantly less symptomatic peptic ulcer disease and gastrointestinal bleeding than low-dose aspirin in average-risk patients 3.
• However, in high-risk patients, clopidogrel is associated with a high incidence of upper gastrointestinal bleeding 4.
• A study found that 12% of patients with a history of non-aspirin-related peptic ulcer disease or aspirin-related gastrointestinal complications developed gastrointestinal bleeding while taking clopidogrel 4.
• The frequencies of hemorrhagic spots, erosions, and peptic ulcers in symptomatic clopidogrel users were 25%, 39%, and 39%, respectively 5.

Apixaban and Peptic Ulcer Disease

• There is no direct evidence in the provided studies regarding the relationship between Apixaban (Eliquis) and peptic ulcer disease.
• However, it is known that anticoagulant therapy, including medications like Apixaban, can increase the risk of gastrointestinal bleeding 6.

Comparison of Clopidogrel and Aspirin

• A study compared the risk of recurrent hospitalization for major gastrointestinal complications in patients at high GI risk who require ongoing antiplatelet therapy with aspirin or clopidogrel, with or without proton pump inhibitors (PPIs) 7.
• The results showed that aspirin plus a PPI was associated with a reduced risk of recurrent hospitalization for major GI complications, but this was not the case for clopidogrel plus a PPI 7.
• Clopidogrel users had a higher frequency of hemorrhagic spots and peptic ulcers compared to aspirin users 5.