Duration of ACE Inhibitor Therapy After Acute Myocardial Infarction
ACE inhibitors should be continued indefinitely (lifelong) in patients with reduced left ventricular ejection fraction (LVEF ≤40%), heart failure, anterior MI, or diabetes after acute myocardial infarction. 1, 2
High-Risk Patients Requiring Indefinite Therapy
For patients with specific high-risk features, the evidence strongly supports lifelong continuation:
LVEF ≤40%: Continue ACE inhibitors indefinitely, as landmark trials (SAVE, AIRE, TRACE) demonstrated sustained mortality reduction over 3-6 years of follow-up, with the TRACE study showing a 27% relative mortality reduction and 15.3 months increased life expectancy when followed for a minimum of 6 years. 1, 2
Heart failure during acute phase: Even if heart failure symptoms resolve, continue indefinitely based on the AIRE trial showing 27% mortality reduction at 15 months, with benefits persisting long-term. 1, 2
Anterior MI: Indefinite therapy is recommended due to higher risk of adverse remodeling and mortality. 1
Diabetes mellitus: Continue indefinitely as this population derives particular benefit from ACE inhibition. 1, 2
Low-Risk Patients: Duration Remains Uncertain
For patients with preserved LVEF (>40%), no heart failure, and uncomplicated MI, the optimal duration is less clear, but a minimum of 4-5 years is reasonable based on available evidence. 1
The 2003 European Society of Cardiology guidelines note that follow-up data from post-infarction studies suggest benefit if ACE inhibitor administration is continued for at least 4-5 years, even in the absence of ventricular dysfunction. 1 However, the 2013 ACC/AHA guidelines acknowledge that "the role of routine long-term ACE inhibitor therapy in low-risk patients after STEMI who have been revascularized and treated with aggressive lipid-lowering therapies is less certain." 1
Practical Algorithm for Duration Decision
At hospital discharge:
- Assess LVEF, presence of heart failure, MI location, and diabetes status 1
If ANY of the following are present, continue indefinitely:
- LVEF ≤40% 1
- Clinical or radiological heart failure during acute phase 1, 2
- Anterior MI 1
- Diabetes mellitus 1, 2
If NONE of the above (low-risk patient):
- Continue for minimum 4-5 years 1
- Reassess ventricular function periodically 3, 4
- Consider discontinuation after 4-5 years if LVEF remains normal and patient remains asymptomatic 1
Timing of Initiation
ACE inhibitors should be started within the first 24 hours of STEMI in indicated patients, as most mortality benefit occurs within the first week. 1, 2, 5 The systematic overview of 98,496 patients demonstrated that early initiation (0-36 hours) prevented approximately 5 deaths per 1000 patients treated, with most benefit observed within the first week. 5
Important Caveats
Monitor closely for:
- Hypotension (17.6% vs 9.3% in controls) 5
- Renal dysfunction (1.3% vs 0.6% in controls) 5
- Hyperkalemia, particularly when combined with aldosterone antagonists 1, 2
Contraindications include:
- Bilateral renal artery stenosis 1
- History of worsening renal function with ACE inhibitor exposure 1
- Cardiogenic shock or severe hypotension 1
For ACE inhibitor-intolerant patients: Use an ARB (preferably valsartan) as an alternative, which showed non-inferiority to captopril in the VALIANT trial. 1, 2
Evidence Quality
The recommendation for indefinite therapy in high-risk patients is based on Class I, Level A evidence from multiple landmark trials including SAVE, AIRE, and TRACE, with consistent findings across studies showing sustained benefit over years of follow-up. 1, 6 The uncertainty regarding duration in low-risk patients reflects the absence of prospective trials specifically addressing this question. 1