ACE Inhibitors and ARBs: Mechanism and Clinical Applications
ACE inhibitors and ARBs are two classes of medications that target the renin-angiotensin-aldosterone system (RAAS) to reduce blood pressure and provide cardiovascular and renal protection. 1
Mechanism of Action
- ACE Inhibitors work by inhibiting angiotensin-converting enzyme (ACE), which prevents the conversion of angiotensin I to the vasoconstrictor angiotensin II, leading to decreased vasopressor activity and decreased aldosterone secretion 2, 3
- ARBs work by selectively blocking the binding of angiotensin II to the AT1 receptor found in various tissues (vascular smooth muscle, adrenal gland), preventing the vasoconstrictor and aldosterone-secreting effects of angiotensin II 4
- A key difference is that ACE inhibitors also inhibit the degradation of bradykinin (as ACE is identical to kininase), which may contribute to their therapeutic effects but also causes side effects like cough 2, 3, 5
Clinical Applications
Hypertension
- Both ACE inhibitors and ARBs are recommended as first-line therapy for hypertension 1, 6
- They are particularly beneficial in patients with diabetes and albuminuria/proteinuria, as they reduce progression to more advanced kidney disease 1, 6
- ARBs are recommended for patients who cannot tolerate ACE inhibitors due to cough or angioedema 6, 7
Heart Failure
- In heart failure with reduced ejection fraction (HFrEF), ACE inhibitors are recommended as first-line therapy 1, 8
- ARBs (specifically valsartan and candesartan) are recommended for patients who are intolerant to ACE inhibitors 6, 8
- In patients with structural heart disease or LV dysfunction without HF symptoms (Stage B), ACE inhibitors or ARBs help prevent symptomatic HF and reduce mortality 1
Post-Myocardial Infarction
- ACE inhibitors are recommended for patients with a history of MI and reduced ejection fraction to prevent symptomatic heart failure and reduce mortality 1
- Valsartan has demonstrated efficacy specifically in post-MI left ventricular dysfunction 8
Comparative Efficacy and Safety
- There is no significant difference between ACE inhibitors and ARBs regarding total mortality, cardiovascular mortality, or cardiovascular events 7, 9
- ARBs have fewer withdrawal rates due to adverse events compared to ACE inhibitors (ARR 1.8%, NNTB 55 over 4.1 years) 9
- The most common adverse effect of ACE inhibitors is dry cough (due to bradykinin accumulation), which is not seen with ARBs 5, 9, 10
- Angioedema is a rare but potentially serious adverse effect of ACE inhibitors that occurs less frequently with ARBs 7, 10
Important Considerations
- Combination of an ACE inhibitor with an ARB is generally not recommended as it increases adverse effects without providing additional benefits 11, 8
- Both medications can cause hyperkalemia and renal dysfunction, particularly in patients with pre-existing kidney disease 2, 3
- ACE inhibitors and ARBs should be used cautiously in patients with bilateral renal artery stenosis 1
- Both drug classes are contraindicated during pregnancy 2, 4
- In hypertensive patients with normal renal function, ACE inhibitors may cause a small increase in serum potassium (approximately 0.1-0.2 mEq/L) 2, 3
Special Populations
- In Black patients, who often have low-renin hypertension, ACE inhibitors and ARBs may have a smaller average response when used as monotherapy 2, 3
- Combination with a thiazide diuretic enhances blood pressure reduction in all populations, including Black patients 2, 3
- In patients with diabetes and nephropathy, both ACE inhibitors and ARBs are considered first-line therapy for prevention of progression of nephropathy 1