Continuing Education Activity

The Angiotensin converting enzyme (ACE) inhibitors are a class of medication used to treat and manage hypertension, a significant risk factor for coronary disease, heart failure, stroke, along with a number of other cardiovascular conditions including congestive heart failure with reduced ejection fraction (CHFrEF), chronic kidney disease (CKD), Coronary artery disease (CAD) and myocardial infarction (MI). Most cases are primary and not attributable to any specific etiology. ACE is an enzyme involved in the renin-angiotensin-aldosterone system (RAAS). ACE inhibitors are competitive inhibitors of ACE, which block the conversion of Angiotensin I to Angiotensin II. Captopril was the first ACE inhibitor approved for clinical use in 1981. This activity reviews the indications, contraindications, mechanism of action, administration, dosing, adverse events, monitoring, and clinical toxicology of the ACE inhibitors. The CME program aims to provide evidence-based medicine to improve patient care and outcomes. It focuses on strategies to minimize adverse reactions while maximizing the effectiveness of ACE inhibitors. This training will equip healthcare professionals with the knowledge to deliver safe, effective, and individualized care during the administration of ACE inhibitors.

Objectives:

• Identify the mechanism of action of ACE inhibitors.

• Evaluate the adverse drug reactions of ACE inhibitors.

• Determine the classic indications for initiating ACE inhibitor therapy.

• Implement an interprofessional team approach that utilizes evidence-based medicine and a patient-centered approach to enhance patient outcomes.

Indications

FDA Approved Indications

1. Angiotensin-converting enzyme (ACE) inhibitors are useful as adjunctive therapy in systolic heart failure (HF). HF guidelines recommend ACE inhibitors to help prevent heart failure (HF) in patients with a reduced ejection fraction (EF) who also have a history of myocardial infarction (MI), and to prevent HF in any patient with a reduced EF, or to treat patients with heart failure and a reduced EF (HFrEF). The American College of Cardiology and the American Heart Association support the use of ACE inhibitors in patients with HFrEF.[1]

2. ACE inhibitors can be used to treat hypertension either alone or in conjunction with other antihypertensives in adults or children over six years old. Hypertension guidelines recommend initiating ACE inhibitors for hypertension. According to the American College of Cardiology, treatment recommendations exist based on various patient populations.[2] These are:

• Patients with blood pressure 130-139/80-89 with clinical atherosclerotic cardiovascular disease (ASCVD) or estimated 10-year cardiovascular disease(CVD) risk ≥ 10% or BP ≥ 140/90 with no clinical CVD and 10-year ASCVD risk <10%. Clinical CVD is defined as coronary heart disease, congestive heart failure, stroke, and peripheral artery disease.[3][4][3]
• Patients with an in-office or out-of-office BP exceeding 130 mmHg systolic or over 80 mmHg diastolic, and the addition of the following factors:
• Diabetes mellitus
• Chronic kidney disease
• Chronic kidney disease after renal transplant
• Heart failure
• Stable ischemic heart disease
• Peripheral artery disease
• Age 65 or older

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

• Regardless of race or diabetes mellitus status, ACE inhibitors are recommended as initial therapy to improve kidney outcomes.[5]
• In the non-Black population with diabetes mellitus and without CKD, initial antihypertensive therapy should include either a thiazide diuretic, a calcium channel blocker (CCB), an ACE inhibitor, or an angiotensin receptor blocker (ARB).
• In the Black population with diabetes mellitus and without CKD, initial antihypertensive therapy should include a thiazide diuretic or CCB instead of an ACE inhibitor or ARB.
• According to the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 guidelines, renin-angiotensin system inhibitors (RASi), such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, are recommended for individuals with chronic kidney disease (CKD). For patients with CKD and severely increased albuminuria, regardless of diabetes status, ACE inhibitors should be started. For those with moderately increased albuminuria and no diabetes, ACE inhibitors are advised. Additionally, for individuals with moderate-to-severe albuminuria with diabetes, starting ACE inhibitors is strongly recommended.[6]

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 mellitus, 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.
• ACE inhibitors demonstrate efficacy in treatment due to their overall reduction in mortality across multiple disease states. There is evidence of mortality benefits in patients with hypertension, heart failure, Acute MI, and diabetes mellitus.[7][8][9]

Off-Label Uses

ACE inhibitors may delay the progression of nephropathy and reduce the risks of cardiovascular events in hypertensive patients with diabetes mellitus type I and type II. The addition of an ACE inhibitor has shown a significant reduction in serum creatinine in hypertensive and normotensive patients with albuminuria. ACE inhibitor therapy has shown a significant decrease in the progression of diabetic nephropathy.[10][11] Krecak I. et al. found evidence that ACE inhibitors might have renoprotective properties in patients with polycythemia vera.[12] Yao J.et al. discovered that ACE inhibitors improve insulin sensitivity in hypertensive patients with diabetes mellitus compared to angiotensin II receptor blockers.[13] Salmenkari H. et al. found evidence that the use of ACE inhibitors and angiotensin II receptor blockers in patients with inflammatory bowel disease results in fewer hospitalizations, glucocorticoid use, and a milder disease course.[14] The treatment with ACE inhibitors in adult patients with the diagnosis of nonalcoholic fatty liver disease (NAFLD), now also called metabolic dysfunction-associated steatotic liver disease (MASLD), especially those with associated chronic kidney disease, is associated with decreased risk of liver-related events (LRE), defined as the risk of cirrhosis complications and liver cancer.[15][16] Hypertensive patients with Alzheimer's disease (AD) treated with ACE inhibitors demonstrated intact physical capacity, improved hand grip strength, and prevention of neuromuscular junction degradation, as indicated by the maintenance of plasma C-terminal agrin fragment-22 (CAF22) levels.[17] Similar findings of better hand grip strength and gait speed, but low CAF22 levels, were also noted in CHF patients treated with ACE inhibitors.[18] ACE inhibitors are also used in scleroderma renal crisis.[19][20] A recent study found that renin-angiotensin system (RAS) blockers, including ACE inhibitors, provided similar mortality benefits in both Black and non-Black patients with heart failure and reduced ejection fraction. Although the relative reduction in heart failure hospitalizations was smaller in Black patients, the absolute benefit was comparable due to their higher baseline risk.[21] The meta-analysis suggests that renin-angiotensin system inhibitors, including ACE inhibitors, are associated with a reduced mortality rate in patients with atrial fibrillation; however, further large-scale trials are needed to confirm these findings.[22]

Mechanism of Action

The angiotensin-converting enzyme (ACE) is involved in the renin-angiotensin-aldosterone system (RAAS; media item 1) and stimulates the conversion of angiotensin I to angiotensin II. ACE is found in the lung capillaries and the endothelium of the kidneys.[23]  ACE inhibitors are competitive inhibitors of ACE, which prevent 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.[24][7][8][25][8]

It is essential to understand the role of the RAAS hormonal system in depth to appreciate the therapeutic effects of ACE inhibitors and understand why this is a target for hypertensive therapy. Initially, afferent arteriole juxtaglomerular cells synthesize prorenin, which is actively cleaved to renin. Angiotensinogen, produced from the liver, is then cleaved by renin to form angiotensin I. The angiotensin I molecule is converted to angiotensin II by ACE. Angiotensin II is a molecule that has significant actions on various systems. Initially, angiotensin II induces vasoconstriction, which ultimately increases systemic blood pressure.[26] Angiotensin II stimulates the adrenal cortex to produce aldosterone and the pituitary to produce antidiuretic hormone. Aldosterone induces sodium reabsorption and, in turn, water reabsorption through internal mineralocorticoid receptor activity.[27] 

Antidiuretic hormone increases the synthesis of aquaporin-2 channels in the collecting duct, inducing selective reabsorption of water. Actions of angiotensin-II and aldosterone lead to adverse cardiac remodeling. ACE inhibitors prevent adverse cardiac remodeling by reducing the concentrations of angiotensin II and aldosterone.[28]

Clinical Pharmacokinetics

Angiotensin-converting enzyme (ACE) inhibitors exhibit significant variability in their pharmacokinetic properties, including prodrug status, formulation options (oral vs. intravenous), lipophilicity, tissue distribution, and elimination routes. Lisinopril and captopril are not prodrugs and are active without requiring hepatic conversion, making them suitable for patients with hepatic dysfunction. In contrast, enalapril, fosinopril, benazepril, quinapril, and moexipril are prodrugs, requiring hepatic conversion to their active forms (enalaprilat, fosinoprilat, benazeprilat, quinaprilat, and moexiprilat). Fosinopril is unique in that it is eliminated via both renal and hepatic routes, allowing it to be used without dose adjustment in patients with renal impairment. Captopril and moexipril must be administered on an empty stomach, as food can decrease their absorption, which may complicate adherence. Enalaprilat, the only intravenous ACE inhibitor, exhibits a rapid onset of action, making it useful in hypertensive emergencies. Most ACE inhibitors can be dosed once daily; however, captopril requires multiple daily doses. Agents such as benazepril, quinapril, and moexipril may require more frequent dosing due to their lower trough-to-peak ratios. The dialyzability of ACE inhibitors also varies: captopril, enalapril, and lisinopril are effectively removed by hemodialysis. https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/j.1875-9114.1998.tb03121.x#:~:text=Angiotensin%2Dconverting%20enzyme%20(ACE),information%20available%20for%20many%20indications.

Administration

Available Dosage Forms

All ACE inhibitors are prescribed orally, except for enalapril, which can be given intravenously. Enalapril's IV dosage is initially 0.625 to 1.25 mg every 6 hours. Dosage titration can be increased up to 5 mg IV every 6 hours. Geriatric dosing should be initiated at the lower end of the adult dosing regimen. ACE inhibitors are most commonly administered as oral agents; however, intravenous forms are also available for use. These medications most commonly end with the suffix '-pril.' Examples include lisinopril, ramipril, and captopril.

ACE Inhibitors are Classified into Three Groups According to Chemical Structure

• Sulfhydryl-containing ACE inhibitor. Captopril –  Hypertension therapy is 25 mg, either BID or TID, with a maximum of 450 mg. Heart failure therapy is 6.25 mg TID, with a maximum of 450 mg.
• Phosphorus-containing ACE inhibitor. Fosinopril – The recommended hypertension therapy dose is 10 mg, increasing to a maximum dose of 80 mg. It may be divided into two equal doses throughout the day to help control blood pressure. Heart failure therapy is 5 to 10 mg daily to a maximum dose of 40 mg.[1]
• Dicarboxylic-containing ACE inhibitors: Benazepril, enalapril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril[23]

General Dosing Information

There should be a dosage decrease in patients with heart failure, salt-depleted patients, and/or renal impairment. 

Lisinopril and captopril are the only ACE inhibitors that do not require activation in the body to be effective. All the other ACE inhibitors are prodrugs and require activation. Most reach peak serum levels within 1 hour after ingestion. Since most of the activation occurs in the liver, a non-prodrug form is preferable in patients with underlying liver issues.[29] Withholding RAAS inhibitors, including ACE inhibitors, before noncardiac surgery reduces intraoperative hypotension and acute kidney injury with nonsignificant effects on mortality and major adverse cardiovascular events (MACE).[30]

Specific Patient Populations

Breastfeeding considerations: ACE inhibitors generally have poor bioavailability but are metabolised to active metabolites with long half-lives. Lisinopril is an exception, as it lacks an active metabolite and has a shorter half-life. Although its pharmacokinetic profile appears favourable, there is no data supporting its use during breastfeeding. For other ACE inhibitors, evidence shows only small amounts of the parent drug and its metabolite in breast milk. Enalapril is often preferred due to the most published data, with one study showing infant exposure at 0.16 % of the maternal dose. ACE inhibitors may be used cautiously during breastfeeding.[31]

Specific Patient Populations

Hepatic impairment: Lisinopril and Captopril stand out as the sole ACE inhibitors that are not prodrugs, and thus are suitable in hepatic impairment.[32] 

Renal impairment: In patients with renal impairment, fosinopril is a suitable choice due to its dual renal and fecal excretion. Other ACE inhibitors, such as captopril, enalapril, lisinopril, and ramipril, can also be used in dialysis.[33]

Pregnancy considerations: ACE inhibitors are contraindicated during the second and third trimesters because of a well-documented fetopathy. The risks of first-trimester exposure are less well-defined. A strong association between 1^st trimester ACE inhibitors exposure and major cardiovascular and neurological malformations has been described.[34]

Breastfeeding considerations: ACE inhibitors generally have poor bioavailability but are metabolised to active metabolites with long half-lives. For other ACE inhibitors, evidence indicates that only small amounts of the parent drug and its metabolite are present in breast milk. Enalapril is often preferred due to the most published data, with the least infant exposure. ACE inhibitors may be used cautiously during breastfeeding.[31] ACE inhibitors are typically considered safe for lactating mothers, except in cases involving premature birth or renal failure of the newborn. [20][31]

Pediatric patients: ACE inhibitors commonly used for pediatric hypertension include captopril, lisinopril, and enalapril.[35]

Older patients: In older patients, avoid initiating ACE inhibitors if dehydration is present. Regular monitoring of serum creatinine and potassium levels is necessary.[36]

Adverse Effects

Most Common

• Dry Cough (10% to 20%)
• Dizziness (12% to 19%)
• Hypotension (7% to 11%)
• Increased BUN and creatinine (2% to 11%)
• Syncope (5% to 7%)
• Hyperkalemia (2% to 6%)

Dry Cough: Commonly, patients on ACE inhibitors have reported dry cough between the one week of initiation and up to six months. Some sources cite up to one year after initiation. Discontinuing therapy usually resolves the cough 1 to 4 days after, but it can be prolonged for up to a month.[37] The concern for dry cough with therapy initiation is a decrease in the patient's medication adherence. Additionally, there is an increased propensity to develop bronchospasm in these patients.[38] 

ACE metabolizes bradykinin and other local molecules. Inhibiting ACE in the lung increases the concentration of kinins, causing bronchial irritation.[39] The use of ACE inhibitors raises the risk of symptoms of airway obstruction and increases the risk of asthma or bronchial asthma worse.[23] After discontinuation of ACE inhibitor therapy, an angiotensin receptor blocker (ARB) can be initiated as an alternate therapy. ARBs have a lower incidence of cough recurrence than reinitiating ACE inhibitor therapy.[40] If cough recurs on ARB therapy, switch to a different drug class entirely.

Angioedema: Angioedema is a rare but potentially life-threatening side effect of ACE inhibitor use. Angioedema is an adverse drug reaction characterized by swelling of the face, lips, and upper airway in an episodic nature. The inflammation creates difficulty in the patient's ability to maintain an airway; therefore, endotracheal intubation can be necessary to secure the airway. The mechanism of angioedema is thought to involve an excessive accumulation of bradykinins in select individuals. Bradykinin induces prominent vasodilation and plasma extravasation into the local tissue. Therefore, the primary treatment of ACE inhibitor-induced angioedema is the discontinuation of ACE inhibitor therapy. It is also suggested to avoid ACE inhibitor therapy in individuals with hereditary angioedema or a history of angioedema episodes. Ghouse J. et al. conducted a genome-wide association study on patients who developed ACE inhibitor-related angioedema.[41] The investigators found variants located near the bradykinin receptor B2 gene. Tranexamic acid can limit the synthesis of bradykinin by interrupting plasminogen activation, and can be used for the treatment of ACE inhibitor-induced angioedema, although further research is needed.[42]

Hyperkalemia: Hyperkalemia from ACE inhibitors directly results from its mechanism of action. The blockade of angiotensin II prevents the downstream secretion of aldosterone. Aldosterone causes reabsorption of sodium and, subsequently, water. Consequently, protons and potassium get secreted into the urine. Without potassium secretion through aldosterone, potassium can easily increase in patients on ACE inhibitors.[43] Co-morbidities that decrease kidney function or medications that cause potassium retention can increase the risk of hyperkalemia.

Increased BUN and creatinine: A slight reduction of glomerular filtration rate (GFR) is common when initiating therapy. Patients with heart failure, chronic kidney disease, and bilateral renal artery stenosis with poor renal perfusion can further reduce GFR, which mandates discontinuation of ACE inhibitor therapy.[44]

Hypotension: Hypotension can cause intolerance to therapy, leading to discontinuation in a small population of patients, which is more common in patients with increased renin baseline concentrations. Allowing the repletion of fluids and discontinuing diuretic medication before therapy can minimize hypotensive episodes.[45]

Dizziness: Dizziness is a common adverse drug reaction associated with ACE inhibitor therapy, which can be mitigated by maintaining adequate volume status and avoiding concomitant diuretic therapy.[9][46]

Post-marketing surveillance: Significant adverse events are reported in less than one percent of the population in post-marketing surveillance. These adverse drug reactions include anaphylactoid reactions, cardiac arrest, cutaneous pseudolymphoma, eosinophilic pneumonitis, hepatic necrosis, hyponatremia, intestinal angioedema, malignant neoplasm of the lung, pulmonary embolism, systemic lupus erythematosus, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and transient ischemic attack.

Khera R. et al. found no association between ACE inhibitors and angiotensin II receptor blockers in COVID-19 hospitalization and mortality.[47]

ACE inhibition in the lungs can cause the accumulation of bradykinin. Angiogenesis is promoted by the release of vascular endothelial growth factor by bradykinin receptors in human lung cancer tissue. Substance P (SP)/neurokinin (NK)-1 receptor accumulation caused by ACE inhibitors is related to tumor proliferation and angiogenesis.[23] In patients of Asian ethnicity, the use of ACE inhibitors can be a risk factor for lung cancer.[48] However, meta-analysis suggests that renin-angiotensin system inhibitors (RASIs), including angiotensin-converting enzyme inhibitors (ACE inhibitors), are associated with improved overall and recurrence-free survival in patients with cancer.[49] Additional research is required.

Drug-Drug Interactions

• Sulfonylureas: The combination of ACE inhibitors with sulfonylureas in diabetic patients may increase the risk of hypoglycemia. Regular monitoring of blood glucose is important when both are prescribed together.

• Lithium: ACE inhibitors can reduce lithium clearance by the kidneys, raising the risk of lithium toxicity. Lithium levels and clinical signs of toxicity should be checked frequently during co-administration.

• Magnesium supplements: Magnesium may enhance the blood pressure-lowering effect of ACE inhibitors, particularly in patients with low magnesium levels. Blood pressure and electrolyte levels should be checked periodically.

• Azathioprine: Use of ACE inhibitors with azathioprine has been linked to bone marrow suppression, including anemia and leukopenia. Complete blood counts should be monitored to detect early signs of myelosuppression.

• Allopurinol: Concurrent use may raise the risk of hypersensitivity reactions. Patients should be monitored for skin rashes or systemic allergic symptoms.

• Fluconazole: Fluconazole may interact with the metabolism of certain medications, such as losartan; however, when used in combination with ACE inhibitors, it can still increase the risk of hyperkalemia. Electrolyte levels, especially potassium, should be followed.

• Ketoconazole: This antifungal can inhibit liver enzymes responsible for metabolizing drugs, potentially amplifying the effects of drugs taken concurrently. Patients on ACE inhibitors should be monitored for exaggerated responses.

• Bupivacaine: There are reports of severe hypotension and bradycardia during spinal anesthesia with bupivacaine in patients on ACE inhibitors. Close intraoperative monitoring is advised.[50]

Contraindications

Absolute Contraindications

• Hypersensitivity reactions- 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 inhibitors, idiopathic or hereditary angioedema, or current use of aliskiren in a patient with diabetes mellitus. Also, consider drugs with cross-reactivity with ACE inhibitors.[51][52]
• Pregnancy -The use of drugs that inhibit the renin-angiotensin system correlates with teratogenic effects such as oligohydramnios, decreased fetal renal function, anuria, renal failure, skull hypoplasia, and death. The proposed mechanism behind oligohydramnios is evident at the level of the fetal kidney. The low-pressure hemodynamics of the fetus become easily disrupted with a decreased amount of angiotensin II. Fetal renal pressure becomes lower, reducing the ability to maintain GFR, leading to oligohydramnios and anuria.[53] Although ACE inhibitors are contraindicated in pregnancy, they can be used in lactation as they do not significantly pass into breast milk.[54][55][54]

Relative Contraindications

Use with great caution in the following situations:

• Patients with abnormal renal function: ACE inhibitors can cause an 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 on an ACE inhibitor. If the renal function starts to decline, the clinician should discontinue the ACE inhibitor immediately.

• Patients with aortic valve stenosis: ACE inhibitors reduce afterload and lead to severe hypotension, so these patients should not receive ACE inhibitors. 

• Patient with hypovolemia: ACE inhibitors can worsen dehydration and hypovolemia, so these patients should not receive treatment with ACE inhibitors.

• Sarcoidosis: ACE inhibitors potentially lead to low ACE concentrations in peripheral blood samples. The clinical interpretation in patients with sarcoidosis receiving ACE inhibitors is not accurate.[56]

• First-Dose Hypotension: Profound first-dose hypotension may occur when ACE inhibitors are introduced to patients with heart failure who are already taking a high dose of loop diuretics.

Monitoring

• Typical parameters to monitor are renal function, i.e., Blood Urea Nitrogen (BUN), serum creatinine, and electrolytes such as potassium.[57]
• If a patient has collagen vascular disease and/or renal impairment, periodically monitor complete blood count with differential to evaluate kidney erythropoietin production.
• In patients with hypotensive effects within 1 to 3 hours of the initial dose, or those with increased dosages or preexisting hepatic impairment, consider baseline hepatic function tests.
• CBC with differential is necessary to evaluate for rare adverse effects of anemia, neutropenia, agranulocytosis, and thrombocytopenia.[58]
• Monitor the vitals routinely to assess the response to treatment.

Toxicity

Signs and Symptoms of Overdose/Toxicity

When used at therapeutic doses, the risk of toxicity is rare. Toxicity is more likely when the drug is used in combination with other antihypertensive drugs or at supratherapeutic doses. Captopril is the only ACE inhibitor to penetrate the blood-brain barrier and potentially cause confusion and lethargy.[59] Combining ACE inhibitors with other antihypertensive drugs can increase adverse effects like hyperkalemia, hypotension, and renal failure. Precaution is required when the patient is given an ACE inhibitor and already receives a potassium-sparing diuretic, NSAIDs, cyclosporine, and anticoagulants.

Management of Overdose/Toxicity

For the majority of patients, the effects of poisoning are mild, and close observation is required. Hospital admission is indicated when symptoms and signs are more severe. Derranged hemodynamic parameters may require supportive therapy with intravenous fluids and inotropic and vasopressor support.[59]

ACE inhibitor overdose can cause hypotension, which can be treated with the use of naloxone, with the presumed mechanism of returning the effect of enkephalinase, which leads to increased degradation of endogenous opioids, which were inhibited by ACE inhibitors. Although very few case reports have been published in the literature suggesting the stated treatment.[60] Severe refractory shock caused by concomitant ACE inhibitor and other antihypertensives toxicity can be treated with Angiotensin II.[61]

Enhancing Healthcare Team Outcomes

Clinicians widely use ACE inhibitors in medicine to treat 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 adverse drug reactions and contraindications. Patients must also be regularly monitored for their renal function and electrolyte concentrations. Healthcare providers should be aware that these agents can produce a chronic dry cough. The clinician should try another class of antihypertensive medication if the patient experiences a dry cough.[24][62][63][64] 

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 potential drug interactions.[65] Nurses should take blood pressure at every visit and chart it accurately, so the clinician can determine if dosing or other changes are required. Nurses can monitor for potential signs of pregnancy and promptly inform the clinician if the patient is pregnant, as ACE inhibitors are absolutely contraindicated in pregnancy.[66]

The clinician must remain informed of these findings from the other interprofessional healthcare team members to take corrective action if necessary. All team members must keep meticulous records of their observations and interventions in the patient's medical record. In summary, the interprofessional team approach between clinicians, nurses, and pharmacists using evidence-based medicine and patient-centered care correlates with reduced morbidity and mortality in patients receiving ACE inhibitor therapy.[67]