From the Guidelines
Enalapril and sacubitril should not be taken together due to the risk of angioedema and other adverse effects. Enalapril is an angiotensin-converting enzyme (ACE) inhibitor, while sacubitril is typically combined with valsartan (an angiotensin receptor blocker) in a single medication called Entresto. According to the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure 1, taking an ACE inhibitor like enalapril with sacubitril can cause dangerous side effects, particularly angioedema, which involves potentially life-threatening swelling.
If transitioning from enalapril to sacubitril/valsartan, a 36-hour washout period is required between stopping the ACE inhibitor and starting the new medication, as recommended by the 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure 1. This waiting period is necessary because both medications affect the renin-angiotensin-aldosterone system, and their simultaneous use can lead to excessive potassium levels, severe hypotension, and kidney dysfunction.
The 2022 AHA/ACC/HFSA guideline for the management of heart failure also supports the use of ARNI over ACE inhibitors in patients with HFrEF, as it has been shown to reduce morbidity and mortality 1. Patients should always consult their healthcare provider before making any changes to their heart failure medication regimen. Key points to consider include:
- The risk of angioedema and other adverse effects associated with concomitant use of ACE inhibitors and sacubitril
- The importance of a 36-hour washout period when transitioning from enalapril to sacubitril/valsartan
- The benefits of using ARNI over ACE inhibitors in patients with HFrEF, as recommended by the 2022 AHA/ACC/HFSA guideline.
From the Research
Enalapril and Secubutril
- Enalapril is an orally active angiotensin-converting enzyme inhibitor that lowers peripheral vascular resistance without causing an increase in heart rate 2.
- It is effective in lowering blood pressure in all grades of essential and renovascular hypertension, and shows similar efficacy to usual therapeutic dosages of hydrochlorothiazide, beta-blockers, and captopril 2, 3.
- Enalapril improves cardiac performance by reducing both preload and afterload, and improves clinical status long-term in patients with severe congestive heart failure resistant to conventional therapy 2, 4.
- The incidence of side effects such as hypotension and reduced renal function can be reduced by careful dosage titration, discontinuation of diuretics, and monitoring of at-risk patients 2.
- Enalapril appears to be well tolerated, with few serious adverse effects being reported, and does not induce bradycardia or adverse effects on laboratory values associated with beta-blockers or diuretics 2, 3.
Comparison with Other Treatments
- Enalapril has been compared with thiazides and beta-blockers, and its effect on systolic blood pressure has been greater than with beta-blockers 3.
- The addition of a thiazide to enalapril treatment increases the proportion of patients who respond with a decrease in diastolic blood pressure 3.
- Enalapril has also been compared with angiotensin II receptor antagonists, which have similar haemodynamic effects but differ in mechanism of action and adverse effects 5.
Clinical Benefits
- Enalapril provides significant haemodynamic, symptomatic, and clinical improvement in patients with congestive heart failure, and reduces mortality when added to established therapy in patients with severe congestive heart failure 4, 6.
- The early effects of starting doses of enalapril are similar to its long-term effects at the target dose, suggesting that enalapril can provide clinical benefits even at lower doses 6.