What is the preferred initial treatment between Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) inhibitors for patients with hypertension or heart failure?

ACE Inhibitors vs ARBs for Hypertension and Heart Failure

ACE inhibitors should be considered as first-line therapy for patients with hypertension or heart failure, with ARBs recommended as an alternative for patients who cannot tolerate ACE inhibitors due to side effects such as cough or angioedema. 1, 2

Efficacy Comparison

• ACE inhibitors are recommended as first-line therapy for patients with heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality (Class I, Level of Evidence A) 1
• ARBs are recommended for patients with HFrEF who are ACE inhibitor intolerant to reduce morbidity and mortality (Class I, Level of Evidence A) 1
• ARBs are reasonable as alternatives to ACE inhibitors as first-line therapy for patients with HFrEF, especially for those already taking ARBs for other indications (Class IIa, Level of Evidence A) 1
• Both ACE inhibitors and ARBs effectively reduce morbidity and mortality by blocking the renin-angiotensin-aldosterone system (RAAS), with ACE inhibitors having been more extensively studied in heart failure and post-MI patients 2, 3

Mechanism of Action and Side Effect Differences

• ACE inhibitors block the conversion of angiotensin I to angiotensin II and inhibit bradykinin breakdown, which contributes to their beneficial vasodilation effects but also causes the characteristic dry cough 2, 3
• ARBs selectively block angiotensin II type 1 receptors without affecting bradykinin metabolism, resulting in fewer side effects 2, 3
• ACE inhibitors commonly cause a persistent dry cough in up to 20% of patients, while ARBs have a significantly lower incidence of cough 3, 4
• In clinical trials comparing ARBs to ACE inhibitors, the incidence of dry cough was significantly greater in the ACE inhibitor group (7.9%) than in groups receiving ARBs (2.6%) or placebo (1.5%) 4

Clinical Decision Algorithm for Hypertension

1. First-line therapy: ACE inhibitors are recommended as initial therapy for hypertension, especially in patients with diabetes, heart failure, or kidney disease 1
2. Alternative if ACE inhibitor not tolerated: Switch to an ARB if the patient develops a persistent dry cough or angioedema with ACE inhibitors 3, 4
3. Initial ARB consideration: Consider ARB as initial therapy when the patient has a history of ACE inhibitor-induced cough or angioedema 3
4. Monitoring: For both medication classes, monitor renal function, potassium levels, and blood pressure closely when initiating therapy 2, 3

Clinical Decision Algorithm for Heart Failure

1. First-line therapy: ACE inhibitors are recommended for patients with HFrEF to reduce morbidity and mortality 1
2. Alternative if ACE inhibitor not tolerated: ARBs are recommended for patients with HFrEF who cannot tolerate ACE inhibitors 1
3. Consideration for initial ARB therapy: ARBs may be reasonable as first-line therapy for patients already taking ARBs for other indications 1
4. Combination therapy: The combination of ACE inhibitor and ARB is generally not recommended due to increased adverse effects without significant additional benefit 3

Important Clinical Considerations

• Start at low doses and titrate gradually to target doses shown to reduce cardiovascular events in clinical trials 2
• Monitor renal function, potassium levels, and blood pressure closely when initiating either ACE inhibitors or ARBs 2, 3
• ARBs should not be initiated within 36 hours of discontinuing an ACE inhibitor due to the risk of overlapping effects 3
• Both medication classes can cause hyperkalemia and renal dysfunction, particularly in patients with pre-existing renal impairment 1

Special Populations

• In patients with diabetes, inhibitors of the renin-angiotensin system may have unique advantages for initial or early therapy of hypertension 1
• For patients with post-myocardial infarction, ACE inhibitors have shown benefits when started within 24 hours in high-risk patients 1
• In patients with diabetic nephropathy, both ACE inhibitors and ARBs have shown renal protective effects 1

Common Pitfalls and Caveats

• Inappropriate use of aldosterone receptor antagonists (which may be used alongside ACE inhibitors or ARBs) is potentially harmful due to risk of life-threatening hyperkalemia or renal insufficiency 1
• Many patients with heart failure receive doses of ACE inhibitors lower than those shown to be effective in clinical trials 5
• ARBs are not superior to ACE inhibitors in heart failure treatment but offer an alternative when ACE inhibitors are not tolerated 6, 7
• Combination therapy with both ACE inhibitor and ARB generally increases adverse effects without providing significant additional benefit 3