Myocardial infarction and ACE inhibitors

Large-scale trials indicate that in post-MI patients between 5 and 45 lives are saved per 1000 patient years of treatment with ACE inhibitors. Greater efficacy is seen if higher risk groups are treated e.g. patients with heart failure.

Therapeutic trials which have tested the efficacy of ACE inhibitors in the management of acute myocardial infarction include the following:

• AIRE
• SAVE
• CONSENSUS II
• GISSI-3
• ISI-4
• SMILE
• TRACE
• OPTIMAAL - actually comparing losartan and captopril

The conclusions are that ACE-inhibitors should be given in the following circumstances:

• when myocardial infarction is, at any time, complicated by left ventricular failure (AIRE)
• in the presence of left ventricular dysfunction (SAVE)

It is probably best to start ACE-inhibition about a week after the myocardial infarction (CONSENSUS II vs. AIRE & SAVE). Earlier administration of within 24 hours of infarction is only advisable is the patient is clinically stable and has a systolic blood pressure greater than 100 mm Hg.

Evidence concerning the benefits of ACE-inhibition in stable coronary heart disease and no apparent heart failure is provided in trials such as HOPE and EUROPA.

• a review of randomized controlled trials in patients with coronary artery disease and absence of heart failure or left ventricular dysfunction concluded that ACE inhibitors reduce total mortality and major cardiovascular end points in these patients (1)

NICE have issued guidance as to the use of ACE inhibitors post myocardial infarction (2):

• people who present acutely with an MI should be offered an ACE inhibitor as soon as they are haemodynamically stable. Continue the ACE inhibitor indefinitely
  
  
• titrate the ACE inhibitor dose upwards at short intervals (for example, every 12-24 hours) before the person leaves hospital until the maximum tolerated or target dose is reached
  • if it is not possible to complete the titration during this time, it should be completed within 4-6 weeks of hospital discharge
    
    
• combined treatment with an ACE inhibitor and an angiotensin II receptor blocker (ARB) should not be offered to people after an MI, unless there are other reasons to use this combination
• after an MI patients who are intolerant to ACE inhibitors should be offered an ARB instead of an ACE inhibitor
  
  
• offer an ACE inhibitor to people who have had an MI more than 12 months ago. Titrate to the maximum tolerated or target dose (over a 4-6-week period) and continue indefinitely
  
  
• offer people who have had an MI more than 12 months ago and who are intolerant to ACE inhibitors an ARB instead of an ACE inhibitor

NICE recommends that all patients with left ventricular dysfunction should be taking an ACE inhibitor (3,4,5):

• ACE inhibitor therapy and beta blocker therapy are both first line
  • offer both angiotensin-converting enzyme (ACE) inhibitors and beta-blockers licensed for heart failure to all patients with heart failure due to left ventricular systolic dysfunction. Use clinical judgement when deciding which drug to start first
• measure serum sodium and potassium, and assess renal function, before and 1 to 2 weeks after starting an ACE inhibitor, and after each dose increment
• measure blood pressure before and after each dose increment of an ACE inhibitor
• once the target or maximum tolerated dose of an ACE inhibitor is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell (5)
  
  
• alternative treatments if ACE inhibitors are not tolerated
  • measure serum sodium and potassium, and assess renal function, before and after starting an ARB and after each dose increment
  • measure blood pressure after each dose increment of an ARB. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults
  • once the target or maximum tolerated dose of an ARB is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell (5)

Reference:

1. Danchin N et al.Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials. Arch Intern Med 2006;166:787-96.
2. NICE (2020). Acute coronary syndromes.
3. NICE (May 2013). Secondary prevention in primary and secondary care for patients following a myocardial infarction
4. NICE (August 2010). Chronic heart failure
5. NICE (September 2018).Chronic heart failure in adults: diagnosis and management