What is the preferred initial treatment between Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) for patients with hypertension or heart failure, considering potential side effects and comorbidities such as diabetes or chronic kidney disease?

ACE Inhibitors vs ARBs: Clinical Selection

ACE inhibitors should be the first-line choice for most patients with hypertension, heart failure, or diabetic nephropathy, with ARBs reserved as alternatives when ACE inhibitors are not tolerated due to cough or angioedema. 1, 2

Primary Treatment Algorithm

Initial Drug Selection

• Start with an ACE inhibitor for hypertension, heart failure with reduced ejection fraction, post-myocardial infarction with LV dysfunction, and diabetic nephropathy 1
• Switch to an ARB only if the patient develops persistent dry cough or angioedema on ACE inhibitor therapy 2, 3
• Both drug classes demonstrate equivalent efficacy for blood pressure reduction, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease 4

Heart Failure Considerations

• ACE inhibitors are superior to ARBs in patients with congestive heart failure, showing better outcomes when directly compared 1
• If ACE inhibitors are not tolerated, ARBs (specifically candesartan or valsartan) are recommended alternatives that reduce mortality and hospitalizations 2, 3
• Do not add an ARB to an adequate-dose ACE inhibitor in heart failure—there is no evidence of added benefit and increased risk of adverse effects 2, 3

Diabetic Nephropathy and Renal Protection

For Type 1 Diabetes:

• ACE inhibitors are first-line therapy for preventing and slowing progression of nephropathy 1, 2

For Type 2 Diabetes:

• Both ACE inhibitors and ARBs are first-line options 1, 2
• Losartan (50-100 mg daily) or irbesartan (150-300 mg daily) have the strongest renal outcome evidence for macroalbuminuria 5
• For patients with urine albumin-to-creatinine ratio ≥300 mg/g, ACE inhibitors or ARBs are strongly recommended 1
• For patients with urine albumin-to-creatinine ratio 30-299 mg/g, ACE inhibitors or ARBs are suggested 1

Specific Clinical Scenarios

Hypertension Management

• Blood pressure 130-139/80-89 mmHg: Lifestyle therapy for maximum 3 months, then add ACE inhibitor or ARB if targets not achieved 1
• Blood pressure ≥140/90 mmHg: Initiate drug therapy immediately with ACE inhibitor or ARB alongside lifestyle modifications 1
• Blood pressure ≥160/100 mmHg: Begin with combination therapy using two drugs from different classes 1
• Target blood pressure in diabetic patients is <130/80 mmHg 1

Post-Myocardial Infarction

• ACE inhibitors should be started and continued indefinitely in clinically stable patients with LV ejection fraction <40% 1, 6
• ARBs are indicated for patients with LV failure or dysfunction post-MI who are ACE inhibitor intolerant 1, 3

Coronary Artery Disease

• ACE inhibitors or ARBs are recommended for patients with coronary artery disease and hypertension 1
• In hypertensive patients with CAD, ACE inhibitors generally attenuate myocardial ischemia 7

Critical Safety Considerations and Monitoring

Initiation Protocol

• Do not initiate if serum potassium >5.0 mmol/L or creatinine >250 μmol/L until corrected 2
• Start with the lowest dose, particularly in elderly patients 2
• Check blood pressure, serum creatinine, and potassium within 1-2 weeks after initiation and after each dose increase 2, 5
• Monitor renal function and serum potassium at least annually 1

Acceptable Changes After Initiation

• A slight reduction in glomerular filtration rate at onset is acceptable and correlates with better long-term renal protection 8
• Continue therapy unless serum creatinine rises by more than 30% within 4 weeks 5
• In patients with eGFR <30 mL/min/1.73 m², continuation of ACE inhibitor or ARB may provide cardiovascular benefit without significantly increasing risk of end-stage kidney disease 1

Combination Therapy Pitfalls

Never combine:

• ARB + ACE inhibitor + aldosterone antagonist—dramatically increases risks of renal dysfunction and hyperkalemia without mortality benefit 2, 5
• ARB + ACE inhibitor in general—no evidence of added benefit with increased adverse events 1, 2, 5

Appropriate combinations:

• ACE inhibitor or ARB + thiazide-like diuretic (chlorthalidone or indapamide preferred) 1
• ACE inhibitor or ARB + dihydropyridine calcium channel blocker 1
• Multiple drugs are generally required to achieve blood pressure targets 1

Adverse Event Profile

ACE Inhibitor-Specific Issues

• Persistent dry cough occurs commonly and always resolves after discontinuation 9
• Angioedema is a rare but serious complication that can occur at any time during treatment 9
• Overall withdrawal rates due to adverse events are lower with ARBs than ACE inhibitors 4

Shared Risks

• Both classes can cause hyperkalemia, particularly with concomitant use of potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes 9
• Both are absolutely contraindicated in pregnancy due to fetal toxicity 5
• Avoid in bilateral renal artery stenosis 5

Resistant Hypertension

• If blood pressure remains ≥140/90 mmHg despite ACE inhibitor or ARB + diuretic + calcium channel blocker, add a mineralocorticoid receptor antagonist 1
• Monitor potassium closely when adding mineralocorticoid receptor antagonist to ACE inhibitor or ARB 1