ACE Inhibitors

Article Author:
Amandeep Goyal
Article Author (Archived):
Austin Cusick
Article Editor:
Blair Thielemier
10/8/2019 6:41:40 PM
PubMed Link:
ACE Inhibitors


FDA approved

1. ACE inhibitors are useful as adjunctive therapy in systolic heart failure (HF). HF guidelines recommend ACE inhibitors to help prevent HF in patients with a reduced ejection fraction (EF) who also have a history of myocardial infarction (MI), to prevent HF in any patient with a reduced ejection fraction or to treat patients with HF and reduced EF.

2. ACE inhibitors can be used for the treatment of hypertension (HTN) either alone or in conjunction with other antihypertensives in adults or children greater than 6 years old. Hypertension guidelines recommend initiation of ACE inhibitors for the management of HTN to lower blood pressure (BP) in the following patients:

  • Patients under 60 years of age with SBP = 140 mm Hg or DBP is = 90 mm Hg. The goal of therapy is SBP less than 140 mm Hg and DBP less than 90 mm Hg.
  • Patients = 18 years of age with diabetes and SBP = 140 mm Hg or DBP = 90 mm Hg. The goal of therapy is SBP under 140 mm Hg and DBP below 90 mm Hg.
  • Patients = 18 years of age with chronic kidney disease (CKD) and SBP = 140 mm Hg or DBP = 90 mm Hg. The goal of therapy is SBP less than 140 mm Hg and DBP less than 90 mm Hg.

3. Patients with chronic kidney disease (CKD) and HTN:

  • Regardless of race or diabetes status, ACE inhibitors are recommended as initial therapy to improve kidney outcomes.
  • In the non-Black population with diabetes and without CKD, initial antihypertensive therapy should include either thiazide diuretic, calcium channel blocker (CCB), ACE inhibitor, or angiotensin receptor blocker (ARB).
  • In the Black population with diabetes and without CKD, initial antihypertensive therapy should include either a thiazide diuretic or CCB instead of an ACE inhibitor or ARB.

4. Patients with coronary artery disease (CAD) and HTN:

  • ACE inhibitors are recommended as part of a regimen in patients with HTN and chronic stable angina if there is a history of left ventricular dysfunction, diabetes, or CKD.

5. Patients with ST-elevated myocardial infarction (STEMI):

  • ACE inhibitors should be initiated within 24 hours of all STEMI, specifically in patients with anterior MI, heart failure, or left ventricular (LV) ejection fraction (EF) of 40% or less.

Non-FDA approved

May delay the progression of nephropathy and reduce the risks of cardiovascular events in hypertensive patients with diabetes type I and type II.

Mechanism of Action

ACE is involved in the renin-angiotensin system (RAS) and stimulates the conversion of angiotensin I to angiotensin II. ACE inhibitors are competitive inhibitors of ACE, which prevents the conversion of angiotensin I to angiotensin II. Angiotensin II acts as a potent vasoconstrictor that, when inhibited, can reduce blood pressure by dilating vessels and decreasing aldosterone secretion.[1][2][3]


ACE inhibitors are most commonly oral agents, but intravenous forms are available.

Adverse Effects

Most Common Adverse Reactions

  • Dizziness (12% to 19%)
  • Hypotension (7% to 11%)
  • Increased BUN and Cr (2% to 11%)
  • Syncope (5% to 7%)
  • Hyperkalemia (2% to 6%)

One percent to 10%: flushing, orthostatic effect, chest pain, altered sense of smell, fatigue, headache, alopecia, diaphoresis, erythema, pruritus, skin photosensitivity, Steven-Johnson Syndrome, toxic epidermal necrolysis, urticaria, diabetes mellitus, gout, SIADH, constipation, diarrhea, dysgeusia, flatulence, pancreatitis, xerostomia, impotence, bone marrow suppression, hemolytic anemia, leukopenia, neutropenia, thrombocytopenia, common cold, weakness, blurred vision, diplopia, photophobia, vision loss, tinnitus, cough.[4][5]

Any Injury

Less than 1%: Acute renal failure, anaphylactoid reactions, angioedema, anuria, arthralgia, arthritis, asthma, ataxia, azotemia, bronchitis, bronchospasm, cardiac arrest, cardiac arrhythmia, cerebrovascular accident, chills, confusion, cutaneous pseudolymphoma, dehydration, drowsiness, dyspepsia, dyspnea, dysuria, eosinophilia, eosinophilic pneumonitis, epistaxis, facial edema, fever, gastritis, hallucination, heartburn, hemoptysis, hepatic necrosis, hepatitis, herpes zoster, hypersomnia, hypervolemia, hypoglycemia, hyponatremia, increased erythrocyte sedimentation rate, insomnia, intestinal angioedema, irritability, laryngitis, leukocytosis, malaise, malignant neoplasm of lung, mastalgia, memory impairment, mood changes, muscle spasm, musculoskeletal pain, myalgia, myocardial infarction, oliguria, orthopnea, orthostatic hypotension, palpitations, paresthesia, paroxysmal nocturnal dyspnea, pemphigus, peripheral edema, peripheral neuropathy, pharyngitis, pleural effusion, pneumonia, positive ANA titer, psoriasis, pulmonary embolism, pulmonary infarct, pulmonary infiltrates, pyelonephritis, rhinitis, rhinorrhea, sinusitis, skin infection, skin lesion, skin rash, sore throat, systemic lupus erythematosus, transient ischemic attacks, tremor, uremia, urinary tract infection, vasculitis, vertigo, viral infection, visual hallucination, weight gain, weight loss, wheezing.


The use of drugs that inhibit the renin-angiotensin system are associated with teratogenic effects such as oligohydramnios, decreased fetal renal function, anuria, renal failure, skull hypoplasia, and death.


ACE inhibitors are contraindicated in a patient with a history of hypersensitivity to any ACE inhibitor or component of the formulation, angioedema related to previous treatment with ACE inhibitor, idiopathic or hereditary angioedema, or current use of aliskiren in a patient with diabetes mellitus. Also, consider drugs with cross-reactivity with ACE inhibitors.[6][7]

ACE inhibitors are not recommended in pregnant patients and require discontinuation as soon as pregnancy is detected.

Relative ContraindicationsUse with great caution in the following situations:

  • Patients with abnormal renal function. ACE inhibitors can cause elevation of potassium and worsen renal function in patients already on ACE inhibitors. If the patient has an abnormal but stable renal function, close monitoring is required while he or she is on an ACE inhibitor. If the renal function starts to decline, the clinician should discontinue the ACE inhibitor immediately.
  • Patients with aortic valve stenosis should not be administered afterload reducers like ACE inhibitors because it can lead to severe hypotension.
  • Similarly, patients who are dehydrated or have hypovolemia should not receive treatment with ACE inhibitors.


Common parameters to monitor are BUN, serum creatinine, renal function, WBC, and potassium. If a patient has collagen vascular disease and/or renal impairment, periodically monitor complete blood count with differential. In patients with hypotensive effects within 1 to 3 hours of initial dose or with increased dosages or preexisting hepatic impairment, consider baseline hepatic function tests.


When used at therapeutic doses, the risk of toxicity is rare. Toxicity is more likely when the drug is used in combination or at supratherapeutic doses.

When combining ACE inhibitors with other antihypertensive drugs, they have the potential to increase side effects like hyperkalemia, hypotension, and renal failure. One should pay more attention when the patient is given an ACE inhibitor and is already on a potassium-sparing diuretic, NSAIDs, cyclosporine, and anticoagulants.

All the presently available ACE inhibitors have similar antihypertensive effects at equivalent doses. The only ACE inhibitor that is different is captopril. This agent has a short duration of action and is more likely to induce side effects. It is the only ACE inhibitor to penetrate the blood-brain barrier and potentially cause confusion and lethargy.

Enhancing Healthcare Team Outcomes

Clinicians widely use ACE inhibitors in medicine for the treatment of hypertension, heart failure, and patients with chronic kidney disease. While effective, healthcare workers (nurse practitioners, physicians, and pharmacists) who prescribe these agents should be aware of their side effects and limitations. Patients also need to be monitored for their renal function and electrolyte levels regularly. Finally, the healthcare worker should be aware that these agents can produce a chronic dry cough, and the clinician should try another class of antihypertensive medication.[1][8][9][10]

Even though ACE inhibitors are among the oldest drug classes available, there is a threat that familiarity can lead to carelessness. That is why, like any other drug, these agents require the oversight and coordination of an interprofessional team. Pharmacists need to verify that dosing is appropriate, and check for drug interactions. Nursing will monitor and for female patients, emphasize that if they think they are pregnant or trying to get pregnant, that therapy will need to change to accommodate that. Nursing will also be taking blood pressure at every visit, and charting so the prescriber can determine if dosing or other changes may be for hypertensive control. The physician must remain informed by these findings from the other members of the interprofessional healthcare team, so he can take corrective action if necessary. Communication and collaboration among healthcare team members will make ACE inhibitor therapy more effective, leading to better patient outcomes. [Level V]


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