ACE Inhibitors

Article Author:
Amandeep Goyal
Article Author (Archived):
Alberto Goizueta
Article Editor:
Blair Thielemier
Updated:
7/12/2019 12:32:58 PM
PubMed Link:
ACE Inhibitors

Indications

FDA approved

1. ACE inhibitors can be used 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 < 60 years of age with SBP = 140 mm Hg or DBP is = 90 mm Hg. The goal of therapy is SBP < 140 mm Hg and DBP < 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 < 140 mm Hg and DBP < 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 < 140 mm Hg and DBP < 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]

Administration

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.

Pregnancy

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.

Contraindications

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 should be discontinued 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 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 ACE inhibitor should be discontinued 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 be treated with ACE inhibitors

Monitoring

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.

Toxicity

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 ACE inhibitors are combined 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 prescribed 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 induce confusion and lethargy.

Enhancing Healthcare Team Outcomes

ACE inhibitors are widely used 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 on a regular basis. Finally, the healthcare worker should be aware that these agents can produce a dry chronic cough and another class of antihypertensive should be used.[1][8][9][10]


References

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[2] Knežević T,Gellineo L,Jelaković A,Premužić V,Dika Ž,Laganović M,Jelaković B, Treatment of hypertension induced albuminuria. Current pharmaceutical design. 2018 Nov 26     [PubMed PMID: 30479206]
[3] Hradec J, Pharmacological therapy for chronic heart failure. Vnitrni lekarstvi. 2018 Fall     [PubMed PMID: 30441998]
[4] Leru PM,Anton VF,Bumbea H, Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2018     [PubMed PMID: 30386386]
[5] Sachs B,Meier T,Nöthen MM,Stieber C,Stingl J, [Drug-induced angioedema : Focus on bradykinin]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2018 Apr     [PubMed PMID: 29392343]
[6] Wilkins B,Hullikunte S,Simmonds M,Sasse A,Larsen PD,Harding SA, Improving the Prescribing Gap For Guideline Recommended Medications Post Myocardial Infarction. Heart, lung     [PubMed PMID: 29523466]
[7] Shaikh A, A Practical Approach to Hypertension Management in Diabetes. Diabetes therapy : research, treatment and education of diabetes and related disorders. 2017 Oct     [PubMed PMID: 28929319]
[8] Alzahrani T,Tiu J,Panjrath G,Solomon A, The effect of angiotensin-converting enzyme inhibitors on clinical outcomes in patients with ischemic cardiomyopathy and midrange ejection fraction: a post hoc subgroup analysis from the PEACE trial. Therapeutic advances in cardiovascular disease. 2018 Nov 15     [PubMed PMID: 30442080]
[9] Brar S,Ye F,James MT,Hemmelgarn B,Klarenbach S,Pannu N, Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With Outcomes After Acute Kidney Injury. JAMA internal medicine. 2018 Oct 27     [PubMed PMID: 30422153]
[10] Saglimbene V,Palmer SC,Ruospo M,Natale P,Maione A,Nicolucci A,Vecchio M,Tognoni G,Craig JC,Pellegrini F,Lucisano G,Hegbrant J,Ariano R,Lamacchia O,Sasso A,Morano S,Filardi T,De Cosmo S,Pugliese G,Procaccini DA,Gesualdo L,Palasciano G,Johnson DW,Tonelli M,Strippoli GFM, The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial. Journal of the American Society of Nephrology : JASN. 2018 Nov 12     [PubMed PMID: 30420421]