What is the interaction between Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) with Aspirin (acetylsalicylic acid)?

From the Guidelines

The interaction between ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) with aspirin is clinically significant, but the benefits of combining these medications for patients with established cardiovascular disease, heart failure, or diabetic nephropathy typically outweigh the potential reduction in antihypertensive efficacy, as supported by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1. When used together, aspirin may partially reduce the beneficial effects of ACEIs and ARBs on blood pressure control and cardiovascular protection. This occurs because aspirin inhibits prostaglandin synthesis, which partially counteracts the vasodilatory effects of ACEIs and ARBs. However, this interaction is generally modest at low aspirin doses (75-100 mg daily) commonly used for cardiovascular prevention, and the combination remains safe and appropriate for most patients with cardiovascular disease. Some key points to consider when using ACEIs or ARBs with aspirin include:

• Monitoring blood pressure closely after initiating or changing doses of either medication to ensure adequate blood pressure control is maintained
• Using the lowest effective dose of aspirin to minimize potential interactions
• Considering alternative antiplatelet agents, such as clopidogrel, in patients who require high doses of aspirin or have a history of bleeding complications
• Being aware of the potential for increased risk of bleeding when combining ACEIs or ARBs with aspirin, particularly in patients with renal insufficiency or those taking other medications that increase the risk of bleeding. According to the 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults, retrospective analyses of large-scale clinical trials have suggested that aspirin might interfere with the benefits of ACE inhibition in patients with HF by inhibiting kinin-mediated prostaglandin synthesis 1. However, the 2022 AHA/ACC/HFSA guideline for the management of heart failure suggests that the benefits of combining ACEIs or ARBs with aspirin outweigh the potential risks, and that these medications should be used together in patients with established cardiovascular disease, heart failure, or diabetic nephropathy 1.

From the Research

Interaction of ACEI and ARB with Aspirin

• The interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors has been studied to determine whether the prostacyclin-inhibiting properties of aspirin counteract the bradykinin-induced prostacyclin-stimulating effects of ACE inhibitors 2.
• Studies have shown that low-dose aspirin (80-100 mg) may not have a significant adverse effect on the beneficial effects of ACE inhibitors in heart failure patients, but higher doses of aspirin (325 mg) may attenuate the vasodilatory actions of ACE inhibitors 2.
• A retrospective subgroup analysis of the CONSENSUS II study found that the 6-month mortality rate of patients with acute myocardial infarction who received enalapril and aspirin was higher than the combined mortality rates of patients receiving enalapril or aspirin alone, suggesting a negative interaction between aspirin and ACE inhibitors 2.
• However, the CATS study found that low-dose aspirin (80 or 100 mg) did not attenuate the beneficial effects of captopril after acute myocardial infarction 2.
• There is limited evidence on the interaction between aspirin and angiotensin receptor blockers (ARBs), but studies suggest that ARBs may have a similar effect to ACE inhibitors in patients with hypertension and heart failure 3, 4.

Mechanism of Interaction

• ACE inhibitors decrease the breakdown of bradykinin, a potent vasodilator that stimulates the formation of vasodilatory prostaglandins such as prostacyclin 2.
• Aspirin inhibits the enzyme cyclooxygenase, which decreases the production of prostaglandins, including prostacyclin 2.
• The interaction between aspirin and ACE inhibitors may be related to the balance between the prostacyclin-inhibiting effects of aspirin and the bradykinin-induced prostacyclin-stimulating effects of ACE inhibitors 2.

Clinical Implications

• The use of aspirin and ACE inhibitors or ARBs should be carefully considered in patients with heart failure and hypertension, taking into account the potential benefits and risks of each medication 2, 3, 4.
• Patients with chronic renal insufficiency may be at increased risk of hyperkalemia when using ACE inhibitors or ARBs, and serum potassium monitoring is recommended 4.
• The choice between ACE inhibitors and ARBs should be based on individual patient characteristics and clinical circumstances, including the presence of heart failure, hypertension, and renal disease 3, 4.