What are the effects of high-dose Acetylsalicylic acid (Aspirin) use?

From the Guidelines

High dose aspirin therapy should be avoided due to increased risk of gastrointestinal bleeding and other side effects, and instead, low-dose aspirin (75-100 mg/day) should be used for long-term prevention of serious vascular events in high-risk patients, as recommended by the European Society of Cardiology 1. The use of high dose aspirin is associated with a higher risk of gastrointestinal bleeding, tinnitus, and Reye's syndrome in children with viral illnesses. In contrast, low-dose aspirin has been shown to be effective in preventing serious vascular events in high-risk patients, with a lower risk of side effects. Some of the key points to consider when using aspirin therapy include:

• The dose-dependent GI toxicity of aspirin, which can be mitigated by using the lowest effective dose 1
• The increased risk of GI bleeding with concomitant use of non-aspirin NSAIDs, which can be reduced by using selective COX-2 inhibitors or proton pump inhibitors 1
• The importance of assessing the individual patient's risk of bleeding and cardiovascular events when deciding on aspirin therapy 1
• The potential benefits of aspirin therapy in primary prevention of cardiovascular events in patients with diabetes, as recommended by the American Diabetes Association 1 Overall, the evidence suggests that low-dose aspirin therapy is a safer and more effective option for long-term prevention of serious vascular events in high-risk patients, and that high dose aspirin therapy should be avoided due to the increased risk of side effects. Key considerations for clinicians include:
• Using the lowest effective dose of aspirin to minimize GI toxicity
• Assessing the individual patient's risk of bleeding and cardiovascular events
• Considering alternative therapies, such as selective COX-2 inhibitors or proton pump inhibitors, for patients at high risk of GI bleeding
• Monitoring patients for signs of GI bleeding or other side effects, and adjusting therapy as needed.

From the FDA Drug Label

Warnings Stomach bleeding warning: This product contains an NSAID, which may cause severe stomach bleeding The chance is higher if you... Take other drugs containing prescription or nonprescription NSAIDs (aspirin, ibuprofen, naproxen, or others)

• High dose aspirin use is associated with an increased risk of stomach bleeding.
• The risk of stomach bleeding is higher when taking high doses of aspirin, especially in combination with other NSAIDs or in certain patient populations, such as those over 60 years old or with a history of stomach ulcers or bleeding problems 2.

From the Research

High Dose Aspirin Use

• High dose aspirin use has been studied in various clinical trials to determine its effectiveness in preventing cardiovascular events 3.
• The optimal aspirin dose remains uncertain, but a range of 75-160 mg/day is commonly used for secondary prevention of myocardial infarction, stroke, and vascular death 3.
• Higher doses of aspirin may be required in some patients to achieve desired antithrombotic effects, particularly in those with aspirin-resistant populations 3.
• The use of proton pump inhibitors (PPIs) can reduce gastrointestinal events in patients taking aspirin, regardless of the dose 4.
• PPIs can be used safely in patients taking low-dose or high-dose aspirin, without adversely affecting cardiovascular outcomes 4.

Aspirin Dose and Cardiovascular Events

• The difference between 325 mg/day and 81 mg/day of aspirin may not be significant in terms of cardiovascular benefits, but the potential for adverse bleeding events may be lower with a lower dose 3.
• High-dose aspirin was associated with similar rates of gastrointestinal events and major adverse cardiac events compared to low-dose aspirin in one study 4.
• The use of PPIs can reduce the risk of gastrointestinal bleeding in patients taking aspirin, particularly in those at high risk of bleeding 5.

Combination Therapy with Proton Pump Inhibitors

• Combination therapy with aspirin and PPIs can provide gastroprotection and reduce the risk of gastrointestinal bleeding 6, 5.
• The use of fixed-dose combinations of low-dose aspirin and PPIs can increase medication compliance and improve clinical outcomes 7.
• However, prolonged use of PPIs can lead to serious adverse effects, and physicians need to carefully consider the benefits and risks associated with combination therapy 7.