What is the effect of Enalapril (Angiotensin-Converting Enzyme Inhibitor)?

From the Guidelines

Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, is recommended to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), as evidenced by the 2017 ACC/AHA/HFSA guideline update 1.

Key Points

• The typical starting dose for hypertension is 5 mg once daily, which can be increased gradually to a maximum of 40 mg daily, often divided into two doses.
• For heart failure, treatment usually begins at 2.5 mg twice daily, with gradual increases as needed, as recommended in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1.
• Enalapril works by blocking the conversion of angiotensin I to angiotensin II, thereby reducing blood vessel constriction and decreasing blood pressure.
• Common side effects include dry cough, dizziness, headache, and fatigue, while more serious but rare side effects include angioedema and hyperkalemia.
• Blood pressure, kidney function, and potassium levels should be monitored regularly while taking this medication.
• Pregnant women should not take enalapril as it can cause birth defects, and those planning pregnancy should discuss alternative medications with their healthcare provider.

Benefits and Risks

• Enalapril has been shown to reduce morbidity and mortality in patients with HFrEF, as demonstrated in randomized controlled trials (RCTs) 1.
• The use of ACE inhibitors, including enalapril, is beneficial for patients with prior or current symptoms of chronic HFrEF to reduce morbidity and mortality 1.
• However, enalapril can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium (>5.0 mEq/L) 1.

Monitoring and Titration

• Enalapril should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials, as recommended in the 2017 ACC/AHA/HFSA guideline update 1.
• The target dose for enalapril is 10-20 mg twice daily, as specified in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1.

Alternative Therapies

• Angiotensin receptor blockers (ARBs) and angiotensin receptor-neprilysin inhibitors (ARNIs) are alternative therapies for patients with HFrEF who are intolerant to ACE inhibitors, as discussed in the 2017 ACC/AHA/HFSA guideline update 1 and the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Mechanism of Action Enalapril, after hydrolysis to enalaprilat, inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The effect of Enalapril, an Angiotensin-Converting Enzyme Inhibitor, is to:

• Decrease plasma angiotensin II
• Decrease vasopressor activity
• Decrease aldosterone secretion
• Increase serum potassium
• Lower blood pressure 2

From the Research

Effects of Enalapril on Hypertension

• Enalapril is effective in lowering blood pressure in patients with essential hypertension, with a decrease in diastolic blood pressure of greater than or equal to 10mm Hg in around 70% of patients 3.
• The effect of enalapril on systolic blood pressure is greater than that of beta-blockers 3.
• Enalapril has been compared to thiazides and beta-blockers, and has been shown to be effective in lowering blood pressure in all grades of essential and renovascular hypertension 4.

Effects of Enalapril on Congestive Heart Failure

• Enalapril improves the signs and symptoms associated with congestive heart failure, including an increase in exercise tolerance and an improvement in NYHA cardiac status and prognosis classification 3.
• Enalapril reduces both preload and afterload, and improves cardiac performance in patients with severe congestive heart failure resistant to conventional therapy 4.
• Enalapril has been shown to be well tolerated in patients with congestive heart failure, with few serious adverse effects reported 3, 4.

Pharmacokinetics and Pharmacodynamics of Enalapril

• The clearance of enalapril and elimination of its active metabolite, MK 422, is slower in patients with congestive heart failure compared to patients with hypertension 5.
• The onset of action of enalapril is slower in patients with congestive heart failure, and the duration of action is longer 5.
• Enalapril inhibits serum ACE activity, which correlates with its peak effects on blood pressure 5, 6.

Comparison with Other ACE Inhibitors

• Enalapril has been compared to captopril, and has been shown to have a similar effect on blood pressure and serum ACE activity 6.
• Enalapril has been shown to be as effective as captopril in reducing mortality in patients with heart failure 7.
• Enalapril remains a first-line option for the treatment of heart failure, due to its proven efficacy in reducing mortality and morbidity 7.