What is the recommended dose of ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) and aspirin for patients with acute coronary syndrome (ACS)?

ACE Inhibitors and Aspirin Dosing in Acute Coronary Syndrome

For patients with ACS, start aspirin 162-325 mg (non-enteric coated, chewed) immediately, then maintain at 75-100 mg daily indefinitely; ACE inhibitors should be initiated in all patients with heart failure, left ventricular ejection fraction <0.40, diabetes, or hypertension, with dose titration as tolerated. 1

Aspirin Dosing Strategy

Initial Loading Dose

• Administer 162-325 mg of non-enteric coated, chewable aspirin immediately upon ACS presentation 1
• The aspirin should be chewed (not swallowed whole) to achieve faster onset of antiplatelet action 1
• Give this loading dose even if the patient is already on aspirin therapy 1

Maintenance Dosing

• Use 75-100 mg daily for long-term maintenance 1
• This low-dose regimen (specifically 81 mg in the U.S.) is now preferred over higher doses based on the most recent 2025 ACC/AHA guidelines 1
• When using ticagrelor as the P2Y12 inhibitor, aspirin must be ≤100 mg daily to optimize outcomes 1
• Higher maintenance doses (up to 325 mg daily) showed no additional benefit but increased bleeding risk 1

Critical Dosing Nuance

The 2014 guidelines allowed 81-325 mg daily maintenance 1, but the 2025 guidelines specifically recommend 75-100 mg daily based on newer evidence showing equivalent efficacy with reduced bleeding 1. This represents an important evolution in practice.

ACE Inhibitor Indications and Dosing

Who Should Receive ACE Inhibitors

Class I indications (must receive): 1

• Heart failure present
• Left ventricular ejection fraction <0.40
• Diabetes mellitus
• Hypertension

Class IIb indication (may be reasonable): 1

• All other patients with cardiac or vascular disease

Dosing Approach

• Start with short-acting agents (captopril or enalapril) in patients at risk for hypotension or renal dysfunction 1
• Titrate doses as tolerated after stabilization 1
• Avoid initiation in the first 24 hours if the patient has hypotension or significant renal dysfunction 1
• Recheck creatinine after initiation to monitor for renal function changes 1

Important Contraindications

• Do not use if creatinine >2.5 mg/dL in men or >2.0 mg/dL in women (when considering aldosterone blockade) 1
• Do not use if potassium >5.0 mEq/L 1
• Avoid in patients with cardiogenic shock risk 1

Additional Critical Management Points

Dual Antiplatelet Therapy (DAPT)

Beyond aspirin alone, add a P2Y12 inhibitor for up to 12 months: 1

• Ticagrelor or prasugrel preferred over clopidogrel for NSTE-ACS undergoing PCI 1
• Ticagrelor 180 mg loading, then 90 mg twice daily 1
• Prasugrel 60 mg loading, then 10 mg daily (avoid if prior stroke/TIA) 1
• Clopidogrel 300-600 mg loading, then 75 mg daily (if others unavailable) 1

Aldosterone Blockade

Add aldosterone antagonist if: 1

• Post-MI with LVEF ≤0.40
• Already on therapeutic ACE inhibitor and beta-blocker
• No significant renal dysfunction or hyperkalemia
• Has diabetes or heart failure

Common Pitfall to Avoid

Do not combine ACE inhibitors with ARBs—this increases adverse events without additional benefit 1. Use ARBs only as substitutes in ACE inhibitor-intolerant patients 1.