Unstable angina non ST elevation myocardial infarction inhibitors of RAS

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.; Neil Gheewala, M.D. [3]

Overview

Inhibitors of Renin-Angiotensin-Aldosterone axis include: angiotensin converting enzyme inhibitors (ACEI) (e.g., ramipril, captopril), angiotensin receptor blockers, and aldosterone antagonists.

Mechanism of Benefit

• ACE inhibitors is amongst the class of medications which have been shown to reduce mortality in patients with MI, recent MI and left ventricular dysfunction, and high risk chronic CAD with normal left ventricular function.
• In patients who cannot tolerate ACE inhibitors, angiotensin II receptor blockers can be used.

Clinical Trial Data

HOPE trial was a landmark study in evaluating the role of ramipril (an ACE inhibitor) in a broad category of high risk patients. In this randomized, placebo controlled trial involving 9297 high risk patients, Ramipril was shown to significantly reduce the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT)

Class I

"1. ACE inhibitors should be started and continued indefinitely in all patients with LVEF less than 0.40 and in those with hypertension, diabetes mellitus, or stable CKD, unless contraindicated. (Level of Evidence: A)"

"2. ARBs are recommended in patients with HF or MI with LVEF less than 0.40 who are ACE inhibitor intolerant. (Level of Evidence: A)"

"3. Aldosterone blockade is recommended in patients post–MI without significant renal dysfunction (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) or hyperkalemia (K >5.0 mEq/L) who are receiving therapeutic doses of ACE inhibitor and beta blocker and have a LVEF 0.40 or less, diabetes mellitus, or HF. (Level of Evidence: A)"

Class IIa

"1. ARBs are reasonable in other patients with cardiac or other vascular disease who are ACE inhibitor intolerant. (Level of Evidence: B)"

Class IIb

"1. ACE inhibitors may be reasonable in all other patients with cardiac or other vascular disease. (Level of Evidence: B)"

2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non -ST-Elevation Myocardial Infarction (DO NOT EDIT)

ACE Inhibitor (DO NOT EDIT)

Class I

"1. An Angiotensin Converting Enzyme inhibitor (ACE) should be administered orally within the first 24 h to Unstable angina / NSTEMI patients with pulmonary congestion or LV ejection fraction (LVEF) ≤40%, in the absence of hypotension (systolic blood pressure <100 mmHg or <30 mmHg below baseline) or known contraindications to that class of medications. (Level of Evidence: A)"

"2. An angiotensin receptor blocker should be administered to Unstable angina / NSTEMI patients who are intolerant of ACE inhibitors and have either clinical or radiological signs of heart failure or LVEF ≤40%. (Level of Evidence: A)"

Class III

"1. An intravenous ACE inhibitor should not be given to patients within the first 24 h of Unstable angina / NSTEMI because of the increased risk of hypotension. (A possible exception may be patients with refractory hypertension.) (Level of Evidence: B)"

Class IIa

"1. An ACE inhibitor administered orally within the first 24 h of Unstable angina / NSTEMI can be useful in patients without pulmonary congestion or LVEF ≤40% in the absence of hypotension (systolic blood pressure <100 mm Hg or less than 30 mm Hg below baseline) or known contraindications to that class of medications. (Level of Evidence: B)"