What are the selection criteria for antihypertensive (blood pressure lowering) medications, including Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin II Receptor Blockers (ARBs), Calcium Channel Blockers (CCBs), and thiazide diuretics?

Antihypertensive Selection Criteria

First-line antihypertensive treatment should include drugs from one of four classes: thiazide/thiazide-like diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or long-acting dihydropyridine calcium channel blockers (CCBs), with combination therapy preferred for most patients with confirmed hypertension. 1

General Selection Principles

• First-line antihypertensive medications should be selected from thiazide/thiazide-like diuretics, ACE inhibitors, ARBs, or long-acting dihydropyridine CCBs based on patient characteristics and comorbidities 1
• For most patients with confirmed hypertension (BP ≥140/90 mmHg), combination therapy is recommended as initial treatment, preferably as a single-pill combination to improve adherence 1
• Preferred combinations include a renin-angiotensin system (RAS) blocker (ACE inhibitor or ARB) with either a dihydropyridine CCB or thiazide/thiazide-like diuretic 1
• Combining two RAS blockers (ACE inhibitor and ARB) is not recommended due to increased risk of adverse effects without additional benefit 1

Patient-Specific Selection Criteria

Race/Ethnicity Considerations

• For Black patients: Initial therapy should include a CCB or thiazide diuretic, as ACE inhibitors and ARBs are less effective as monotherapy in this population 1
• For non-Black patients: Any of the four major drug classes can be used as initial therapy 1

Age Considerations

• For patients <55 years: ACE inhibitors or ARBs are often preferred as initial therapy 1
• For patients ≥55 years: CCBs or thiazide diuretics may be more effective as initial therapy 1
• For elderly patients (≥65 years): Treatment should be initiated at lower doses with careful monitoring for orthostatic hypotension and other adverse effects 1

Comorbidity-Based Selection

Diabetes Mellitus

• ACE inhibitors or ARBs are recommended first-line for patients with diabetes 1
• These agents provide renoprotection beyond BP lowering effects 1

Chronic Kidney Disease

• For patients with albuminuria (UACR ≥30 mg/g creatinine), an ACE inhibitor or ARB is recommended as first-line therapy 1
• For patients with UACR ≥300 mg/g creatinine, ACE inhibitors or ARBs should be used at the maximum tolerated dose 1
• Monitor serum creatinine/eGFR and potassium levels at least annually in patients on ACE inhibitors, ARBs, or diuretics 1, 2

Coronary Artery Disease

• ACE inhibitors or ARBs are suggested for patients with coronary artery disease 1
• Non-dihydropyridine CCBs may reduce reinfarction in patients with ischemic heart disease 3

Heart Failure

• ACE inhibitors or ARBs plus beta-blockers are recommended for patients with heart failure with reduced ejection fraction 1
• Thiazide diuretics have been shown to reduce heart failure events compared to CCBs 4

Severity-Based Approach

• For Stage 1 hypertension (140-159/90-99 mmHg): Single-agent therapy may be reasonable, especially in low-risk patients 1
• For Stage 2 hypertension (≥160/100 mmHg) or BP >20/10 mmHg above target: Initiate treatment with two first-line agents of different classes 1

Stepped Care Approach

Initial Treatment Failure

• If BP is not controlled with a two-drug combination, increase to a three-drug combination (typically RAS blocker + CCB + thiazide diuretic), preferably as a single-pill combination 1

Resistant Hypertension

• For patients not meeting BP targets on three classes of medications (including a diuretic), consider adding a mineralocorticoid receptor antagonist (spironolactone) 1
• If spironolactone is not tolerated, consider eplerenone, beta-blockers, alpha-blockers, or centrally acting agents 1

Monitoring and Follow-up

• Monitor BP control monthly after initiation or change in medication until target is reached 1
• For patients on ACE inhibitors, ARBs, or diuretics, monitor serum creatinine/eGFR and potassium at least annually 1, 2
• Follow up every 3-5 months for patients with controlled BP 1

Common Pitfalls and Caveats

• Avoid combining ACE inhibitors with ARBs due to increased risk of hyperkalemia and renal dysfunction without additional benefit 1, 5
• ACE inhibitors are associated with cough (5-20% of patients) and angioedema (rare); ARBs have similar efficacy with fewer of these adverse effects 6
• Thiazide diuretics can cause metabolic abnormalities (hyperglycemia, hypokalemia, hyperuricemia) but remain effective for cardiovascular event prevention 7, 4
• High-fat meals can substantially decrease absorption of some antihypertensives (e.g., aliskiren), so patients should establish a consistent routine for taking medications with regard to meals 5
• For patients with resistant hypertension on a regimen including an ACE inhibitor or ARB plus a mineralocorticoid receptor antagonist, closely monitor for hyperkalemia 1