Low-Dose vs High-Dose Aspirin: Indications and Dosing
Low-dose aspirin (75-100 mg daily) should be used for all maintenance therapy in cardiovascular disease, while high-dose aspirin (162-325 mg) is reserved only as an initial loading dose in acute coronary syndromes, followed immediately by transition to low-dose maintenance therapy. 1
Acute Coronary Syndromes (ACS): Loading Then Low-Dose
For patients presenting with ACS (STEMI or NSTE-ACS), administer a loading dose of 162-325 mg of non-enteric coated aspirin (chewed when possible for faster absorption), followed immediately by daily low-dose aspirin (75-100 mg) for maintenance therapy. 1
- The loading dose should be given as soon as possible on presentation, regardless of whether the patient is already taking aspirin. 1
- Continued use of full-dose aspirin (300-325 mg daily) for 30 days after ACS was not superior to low-dose aspirin (75-100 mg daily) for reducing major adverse cardiovascular events (MACE) but was associated with increased minor and gastrointestinal bleeding. 1
- Non-enteric coated formulations are essential during the acute phase to ensure rapid absorption. 1
Secondary Prevention: Low-Dose Only
For all patients with established atherosclerotic cardiovascular disease (prior MI, stroke, TIA, peripheral vascular disease, or coronary revascularization), use low-dose aspirin 75-162 mg daily indefinitely. 1
- The 75-100 mg daily dose exceeds the minimal effective dose required for complete platelet thromboxane A2 suppression while allowing for interindividual variability in drug response. 1
- When used with ticagrelor as dual antiplatelet therapy, aspirin should be limited to 81 mg daily (not higher doses). 1
- Low-dose aspirin (75 mg daily) may be equally or more effective than higher doses (500-1,500 mg daily), with risk reductions of 29.7% versus 21.4% respectively in cardiovascular events. 1
Primary Prevention: Low-Dose with Caution
For primary prevention in adults 40-70 years at higher ASCVD risk but not at increased bleeding risk, low-dose aspirin (75-100 mg daily) might be considered, though benefits are modest and must be weighed against bleeding risk. 1
- Aspirin should NOT be routinely administered for primary prevention in adults >70 years of age due to increased bleeding risk that outweighs benefits. 1
- For patients with diabetes and elevated cardiovascular risk (age >40 or additional risk factors like hypertension, dyslipidemia, smoking, family history), low-dose aspirin (75-162 mg daily) may be considered for primary prevention. 1
- Aspirin is contraindicated in patients <21 years due to Reye syndrome risk. 1
Why High-Dose Aspirin Is Not Used for Maintenance
High-dose aspirin (≥160 mg daily) is associated with increased bleeding risk without improved cardiovascular outcomes compared to low-dose therapy. 1
- Gastrointestinal bleeding and epigastric pain are dose-dependent side effects that are significantly reduced with low doses. 2, 3, 4
- Even low-dose aspirin carries a 2.6-fold relative risk of upper GI bleeding (annual incidence 0.6%), but this risk increases substantially with higher doses. 2
- The most common low-dose tablet in the U.S. is 81 mg, which provides optimal efficacy with minimal side effects. 1
Key Clinical Pitfalls to Avoid
Never use enteric-coated aspirin for acute coronary syndromes as it has delayed and reduced absorption that compromises immediate antiplatelet effects. 1 Enteric-coated formulations do not reduce the risk of upper GI complications. 2
Do not continue high-dose aspirin beyond the initial loading dose in ACS patients, as this increases bleeding without improving outcomes. 1
Avoid combining aspirin with NSAIDs as this significantly increases GI ulceration and bleeding risk without additional cardiovascular benefit. 1, 3
Special Populations Requiring Gastroprotection
For patients at high GI risk (history of peptic ulcer or GI bleeding, age >70, H. pylori infection, concomitant anticoagulants or other antiplatelet agents), co-prescribe a proton pump inhibitor with low-dose aspirin. 2, 5