What is the recommended order of prescribing antihypertensive medications based on drug class and clinical indication, and what are the contraindications for each class?

Order of Prescribing Antihypertensive Medications by Classification and Indication

First-Line Monotherapy for Uncomplicated Hypertension

For uncomplicated hypertension, initiate treatment with one of five first-line drug classes: thiazide/thiazide-like diuretics (preferred for cost and evidence), ACE inhibitors (avoid in Black patients), ARBs, long-acting calcium channel blockers, or β-blockers (only if age <60 years). 1

The most recent guidelines 1, 2 establish these five classes as equivalent first-line options, though thiazide diuretics maintain preference due to extensive outcome trial data and cost-effectiveness 3. The key distinction is that β-blockers should NOT be used as first-line in patients ≥60 years old 1, and ACE inhibitors should NOT be used as first-line in Black patients 1.

Initial Therapy Algorithm:

Stage 1 Hypertension (130-139/80-89 mmHg):

• Start with single agent monotherapy 2
• Titrate dose, then add second agent if needed

Stage 2 Hypertension (≥140/90 mmHg):

• Initiate with TWO first-line agents from different classes, preferably as single-pill combination 2, 4, 5
• This approach improves adherence and achieves faster BP control

Preferred Combination Therapy

When combining agents, specific pairings demonstrate superior efficacy:

Strongly Recommended Combinations:

• ACE inhibitor + CCB (Grade A) 1
• ARB + CCB (Grade B) 1
• ACE inhibitor or ARB + thiazide diuretic (Grade B) 1
• Thiazide diuretic + dihydropyridine CCB (Grade B) 1, 6

Triple Therapy (if dual therapy fails):

• ACE inhibitor or ARB + CCB + thiazide diuretic 4, 5
• Use single-pill combination when available

Compelling Indications for Specific Drug Classes

Heart Failure with Reduced Ejection Fraction:

• First-line: ACE inhibitor or ARB + β-blocker + diuretic + aldosterone antagonist 7, 1
• Avoid: Non-dihydropyridine CCBs (verapamil, diltiazem) 7

Post-Myocardial Infarction:

• First-line: β-blocker + ACE inhibitor (or ARB if ACE-intolerant) 1
• Add dihydropyridine CCB if β-blockers contraindicated

Coronary Artery Disease:

• First-line: ACE inhibitor or ARB 1
• Preferred combination: ACE inhibitor + dihydropyridine CCB (superior to ACE inhibitor + diuretic) 1

Diabetes with Proteinuria/Nephropathy:

• First-line: ACE inhibitor or ARB 3, 8

Isolated Systolic Hypertension (Elderly):

• First-line: Thiazide diuretic or long-acting dihydropyridine CCB 8, 6

Angina:

• First-line: β-blocker or CCB 8, 1

Benign Prostatic Hypertrophy:

• Compelling indication: α-blocker 3, 8

Absolute Contraindications by Drug Class

ACE Inhibitors:

• Pregnancy (absolute) 3, 8
• Bilateral renal artery stenosis/renovascular disease 8
• History of angioedema

ARBs:

• Pregnancy (absolute) 3, 8
• Bilateral renal artery stenosis 8

β-Blockers:

• Asthma or severe COPD (absolute) 3, 8
• Second or third-degree heart block 8
• Acute decompensated heart failure 8

Thiazide Diuretics:

• Gout (relative, not absolute) 3, 8
• Severe hyponatremia

Non-dihydropyridine CCBs (Verapamil, Diltiazem):

• Heart failure with reduced ejection fraction 8, 7
• Second or third-degree heart block 8

α-Blockers:

• Urinary incontinence 3, 8

Critical Contraindicated Combinations

NEVER combine ACE inhibitor + ARB + renin inhibitor - this triple renin-angiotensin system blockade increases harm without benefit 1, 2. Even dual ACE inhibitor + ARB combination is NOT recommended (Grade A) 1, 6, 1.

Exercise caution combining non-dihydropyridine CCB + β-blocker - risk of excessive bradycardia and heart block 1, 6, 1.

Special Population Considerations

Black Patients:

• Initial therapy: Thiazide diuretic or CCB 4, 5
• Avoid ACE inhibitors as monotherapy (less effective) 1
• Consider dual therapy with diuretic + CCB 4

Elderly (≥60 years):

• Avoid β-blockers as first-line 1
• Prefer thiazide diuretics or long-acting dihydropyridine CCBs 8, 6
• Monitor for orthostatic hypotension

Chronic Kidney Disease:

• ACE inhibitors or ARBs preferred (renoprotective) 3, 8
• Use with caution if eGFR <20 mL/min/1.73m² 1
• Close monitoring required for hyperkalemia and acute kidney injury

Common Pitfalls to Avoid

1. Avoid short-acting nifedipine - associated with adverse cardiovascular outcomes 3, 1
2. Monitor potassium with thiazide monotherapy - hypokalemia increases arrhythmia risk 1, 6, 1
3. Don't use α-blockers as first-line for uncomplicated hypertension - inferior outcomes compared to other classes 1
4. When lowering DBP in CAD patients, be cautious if DBP falls below 60 mmHg - may worsen myocardial ischemia 1