Pharmacological Management

ACE Inhibitors and Angiotensin II Receptor Blockers

Drugs that oppose the effects of angiotensin II have been proven to reduce mortality and morbidity in patients with left ventricular dysfunction (LVD) following myocardial infarction (MI).

Rationale

By inhibiting the formation of angiotensin II (ACE inhibitors) or by blocking its interaction with vascular AT1 receptors (angiotensin II receptor blockers; ARBs), these agents:^1-3

suppress angiotensin II-mediated peripheral vasoconstriction, lowering blood pressure and reducing afterload;
attenuate the effects of the sympathetic nervous system, since angiotensin II stimulates the release of noradrenaline and prevents its reuptake;
oppose angiotensin II-mediated ventricular remodelling.

Evidence

Key trials that support the use of ACE inhibitors and angiotensin II receptor blockers (ARBs) following MI include SAVE (captopril), AIRE (ramipril), SMILE (zofenopril), TRACE (trandolapril) and VALIANT (valsartan).^3-8

Guidelines

European guidelines recommend the use of ACE inhibitors in all patients with STEMI, unless contraindicated.⁹ Following NSTEMI, ACE inhibitors are recommended for patients with LVD (left ventricular ejection fraction ≤40%), and in those with diabetes, hypertension or chronic kidney disease, unless contraindicated.¹⁰ Their use in other groups of patients post-MI should also be considered. There is good evidence to support the use of ramipril and perindopril (and the ARB telmisartan; see below) to prevent cardiovascular deaths and non-fatal ischaemic events in patients with cardiovascular disease but without LVD and/or heart failure.^11-13

Choice of agent

Treatment is generally initiated with an ACE inhibitor, with ARBs being reserved for use in patients who do not tolerate ACE inhibitors (e.g. because of cough). There is little guidance in the literature on drug choice within the ACE inhibitor class, perhaps because there are few clinically important differences between the available agents.¹⁴ In contrast, valsartan has been proven to have comparable efficacy to an ACE inhibitor in patients with post-MI LVD, heart failure, or both.^8,9 Similarly, telmisartan is proven to have similar effects to an ACE inhibitor in those with existing vascular disease or diabetes, but without heart failure.¹³

References:

Kumar P, Clark M. Clinical medicine. 7th ed. Edinburgh: Saunders Elsevier, 2009.
Davies MK, Gibbs CR, Lip GYH. Management: diuretics, ACE inhibitors, and nitrates. In: Gibbs CR, Davies MK, Lip GYH, eds. ABC of heart failure. London: BMJ Books, 2003:25-8.
Pfeffer M, Braunwald E. Ventricular remodelling after myocardial infarction. Circulation 1990;82:1161-72.
Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE investigators. N Engl J Med 1992;327:669-77.
The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effects of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821-8.
Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long?term Evaluation (SMILE) Study Investigators. N Engl J Med 1995;332:80-5.
Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction following myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 1995;333:1670-76.
Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893-906.
van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Eur Heart J 2008;29:2909-45.
Bassand J-P, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J 2007;28:1598-660.
Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting–enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-53.
Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782-8.
The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358:1547-59.
Gerbrandt KR, Yedinak KC. Formulary management of ACE inhibitors. Pharmacoeconomics 1996;10:594?613.

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