In patients with established heart disease, which ACE inhibitor or ARB is most commonly used for blood pressure control?

Most Commonly Used ACE Inhibitors and ARBs for Blood Pressure Control in Heart Disease

In patients with established heart disease, lisinopril is the most commonly used ACE inhibitor, while valsartan and losartan are the most frequently prescribed ARBs for blood pressure control. These agents have the strongest evidence base from large-scale cardiovascular outcomes trials and are recommended as first-line therapy in multiple guideline statements.

ACE Inhibitor Selection for Heart Disease

Lisinopril stands out as a preferred ACE inhibitor based on its extensive evaluation in the landmark ALLHAT trial, which demonstrated equivalent outcomes to other antihypertensive classes in preventing fatal coronary artery disease and nonfatal myocardial infarction in over 33,000 patients 1. When ACE inhibitors cannot be used as first-line therapy, captopril, lisinopril, or ramipril are the evidence-based alternatives 2.

Post-Myocardial Infarction Context

• Captopril has Class I evidence for use in patients post-MI with left ventricular dysfunction, demonstrating a 37% reduction in development of heart failure in the SAVE trial 1
• Ramipril significantly reduces mortality by 27% in patients with clinical heart failure after acute MI, with benefits apparent within 30 days of treatment 3, 1
• Trandolapril was frequently added (in 52-63% of patients) in the INVEST trial when initial therapy with other agents required intensification 1

Dosing Strategy for ACE Inhibitors

• Start with low doses and titrate to the levels used in major trials without undue delay 4
• Target doses should match those proven in clinical trials, as lower doses used in routine practice may compromise outcomes 4

ARB Selection for Heart Disease

Valsartan and losartan have the strongest cardiovascular outcomes data among ARBs for patients with established heart disease.

Evidence-Based ARB Choices

• Valsartan demonstrated equivalence to captopril in the VALIANT trial for high-risk patients after MI, establishing it as a proven alternative when ACE inhibitors are not tolerated 1
• Losartan (50-100 mg daily) is FDA-approved specifically for reducing hard renal endpoints in type 2 diabetic nephropathy and has dose-dependent renoprotective effects 5, 6
• Candesartan is preferred for combination therapy when both ACE inhibitor and ARB are deemed necessary, based on the CHARM-Added trial showing reduced heart failure hospitalization and death 1, 7

Clinical Context for ARB Use

• ARBs are Class I recommended for STEMI patients intolerant of ACE inhibitors who have heart failure or ejection fraction ≤40% 1
• Valsartan or candesartan should be used long-term in patients with symptomatic heart failure who cannot tolerate ACE inhibitors 1
• ARBs reduce major cardiovascular events comparably to ACE inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular disease 1

Critical Decision Algorithm

When to Choose ACE Inhibitor First

ACE inhibitors remain the first-line choice for most patients with hypertension, heart failure, post-MI with LV dysfunction, and diabetic nephropathy 6. The American Heart Association and American Diabetes Association consistently recommend starting with ACE inhibitors before considering ARBs 6.

When to Switch to ARB

Switch to an ARB only if the patient develops:

• Persistent dry cough on ACE inhibitor therapy 6
• Angioedema (absolute contraindication to ACE inhibitors) 6

Specific Agent Selection by Clinical Scenario

For diabetic nephropathy with macroalbuminuria:

• Losartan 50-100 mg daily (first-line, FDA-approved indication) 5, 6
• Irbesartan 150-300 mg daily (equally effective alternative) 5, 6

For heart failure with reduced ejection fraction:

• ACE inhibitor (captopril, enalapril, lisinopril, or ramipril) as first choice 1
• If ACE inhibitor intolerant: valsartan, candesartan, or losartan 7, 1

For post-MI with LV dysfunction:

• Captopril or ramipril (strongest evidence) 1
• Valsartan if ACE inhibitor intolerant 1

Common Pitfalls to Avoid

Never combine ACE inhibitor with ARB in routine practice, as this increases adverse events without mortality benefit, demonstrated in multiple long-term studies including VALIANT 1, 5. The only exception is candesartan added to ACE inhibitor in select heart failure cases based on CHARM-Added 1.

Avoid underdosing: Clinical practice persistently uses lower ACE inhibitor doses than tested in trials, potentially compromising outcomes 4. Titrate to target doses used in major trials (e.g., ramipril 10 mg daily, lisinopril 20-40 mg daily, losartan 100 mg daily).

Monitor appropriately: Check serum creatinine and potassium within 2-4 weeks of initiation or dose increase 5. Continue therapy unless creatinine rises >30% within 4 weeks 5.

Absolute contraindications apply equally: Both ACE inhibitors and ARBs are contraindicated in pregnancy, bilateral renal artery stenosis, and should not be initiated if potassium >5.0 mmol/L or creatinine >250 μmol/L 6, 5.

Combination Therapy Considerations

Most patients require 2-3 antihypertensive agents to reach blood pressure targets 5. When intensification is needed:

• Add thiazide or loop diuretic (60-90% of patients in major ARB trials used concomitant diuretics) 5
• Add long-acting dihydropyridine calcium channel blocker (avoid nondihydropyridines with beta-blockers) 1
• Consider mineralocorticoid receptor antagonist for resistant hypertension, with close potassium monitoring 6