What are the recommended initial regimens for managing hypertension, including dosages for Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin II Receptor Blockers (ARBs), calcium channel blockers, and diuretics?

Initial Antihypertensive Regimens

For non-Black patients, start with low-dose ACE inhibitor or ARB, then add a dihydropyridine calcium channel blocker or thiazide-like diuretic; for Black patients, initiate with an ARB plus dihydropyridine calcium channel blocker or thiazide-like diuretic. 1

Non-Black Patients: Stepwise Algorithm

Step 1: Initial Monotherapy

• Start with low-dose ACE inhibitor or ARB 1, 2
• ACE inhibitor example: Lisinopril 10 mg once daily (usual range 20-40 mg/day) 3
• ARB example: Losartan 50 mg once daily (can increase to 100 mg/day) 4

Step 2: Titration

• Increase to full dose of initial agent if BP not controlled 1
• Lisinopril can be titrated up to 40 mg daily (maximum 80 mg studied but no additional benefit) 3
• Losartan can be increased to 100 mg once daily 4

Step 3: Add Second Agent

• Add dihydropyridine calcium channel blocker (e.g., amlodipine) OR thiazide-like diuretic (e.g., chlorthalidone, indapamide) 1, 2
• If adding hydrochlorothiazide with lisinopril, start with 12.5 mg 3
• The ACE-I/ARB + calcium channel blocker combination may offer superior cardiovascular outcomes compared to ACE-I/ARB + diuretic 2

Step 4: Triple Therapy

• Add the third agent from the remaining class (complete the ACE-I/ARB + CCB + diuretic combination) 1, 5

Step 5: Resistant Hypertension

• Add spironolactone as fourth-line agent 1
• Alternatives if spironolactone not tolerated: amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 1

Black Patients: Modified Algorithm

Step 1: Initial Combination Therapy

• Start with low-dose ARB + dihydropyridine calcium channel blocker OR dihydropyridine calcium channel blocker + thiazide-like diuretic 1
• ACE inhibitors and ARBs are less effective as monotherapy in Black patients (typically low-renin population) 4

Step 2: Titration

• Increase both agents to full dose 1

Step 3: Add Third Agent

• Add thiazide-like diuretic (if not already included) OR ACE-I/ARB (if not already included) 1

Step 4: Resistant Hypertension

• Same as non-Black patients: add spironolactone or alternatives 1

Special Population Considerations

Diabetes with Albuminuria

• Mandatory first-line: ACE inhibitor or ARB to reduce progressive kidney disease 1, 2
• Add thiazide-like diuretic or calcium channel blocker as second agent 1, 6
• Monitor serum creatinine and potassium within 7-14 days after initiation, then annually 2

Established Coronary Artery Disease

• Prefer ACE inhibitor or ARB as first-line 1, 2
• Add beta-blocker for guideline-directed medical therapy if post-MI or angina 1

Heart Failure with Reduced Ejection Fraction

• Start with beta-blocker + ACE inhibitor or ARB 1
• Add mineralocorticoid receptor antagonist and diuretic based on volume status 6
• Avoid non-dihydropyridine calcium channel blockers (verapamil, diltiazem) 1

Elderly Patients (≥80 years) or Frail

• Consider monotherapy initially 1
• Use once-daily dosing and single-pill combinations to improve adherence 1
• Individualize BP targets based on frailty 1

Initial Combination Therapy for Stage 2 Hypertension

For BP ≥160/100 mmHg or >20/10 mmHg above target, initiate with two agents simultaneously 1, 2

Preferred Combinations:

• ACE-I or ARB + dihydropyridine calcium channel blocker 1, 2, 5
• ACE-I or ARB + thiazide-like diuretic 1, 2, 6

The ACCOMPLISH trial demonstrated that ACE-I + calcium channel blocker reduced cardiovascular events by 21% compared to ACE-I + diuretic, despite only 1 mmHg difference in BP control 2

Critical Contraindications and Monitoring

Never Combine:

• ACE inhibitor + ARB - increases hyperkalemia, hypotension, and renal dysfunction without additional benefit 1, 2, 6

Pregnancy Contraindications:

• All ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, and direct renin inhibitors are absolutely contraindicated 2

Monitoring Requirements:

• Check serum creatinine and potassium within 7-14 days after starting ACE-I, ARB, or aldosterone antagonists 2
• Recheck annually thereafter 2
• Achieve BP target within 3 months 1

Common Pitfalls to Avoid

• Underdosing before adding agents: Titrate first agent to full dose before adding second drug (exception: stage 2 hypertension requiring immediate dual therapy) 2
• Ignoring ethnicity: ACE inhibitors and ARBs are less effective in Black patients; prioritize calcium channel blockers or thiazides 1, 2
• Using ACE-I + ARB combinations: This increases adverse effects without benefit 1, 2
• Inadequate initial therapy in markedly elevated BP: Start with two agents if BP ≥160/100 mmHg 1, 2
• Forgetting to simplify regimens: Use once-daily dosing and single-pill combinations to improve adherence 1

Blood Pressure Targets

• General target: <130/80 mmHg for most patients 1, 2
• Minimum reduction: 20/10 mmHg even if target not fully achieved 1
• Elderly/frail patients: Individualize targets, may accept <140/90 mmHg 1