What are the contraindications for first‑line antihypertensive agents in an adult with chronic hypertension?

Contraindications for First-Line Antihypertensive Agents in Chronic Hypertension

Thiazide and Thiazide-Like Diuretics (Hydrochlorothiazide, Chlorthalidone, Indapamide)

Absolute Contraindications:

• History of severe hypersensitivity or anaphylaxis to sulfonamide-derived drugs 1
• Severe hyponatremia (serum sodium <120 mEq/L) or symptomatic hyponatremia 1
• Anuria or severe renal impairment (eGFR <30 mL/min/1.73m²) 1

Relative Contraindications/Cautions:

• Active gout or history of recurrent gout attacks (thiazides increase uric acid levels) 1
• Severe hypokalemia (potassium <3.0 mEq/L) that cannot be corrected 1
• Hypercalcemia (thiazides reduce urinary calcium excretion) 1
• Symptomatic hyperglycemia or poorly controlled diabetes (thiazides can worsen glucose control) 1, 2

ACE Inhibitors (Lisinopril, Enalapril, Ramipril)

Absolute Contraindications:

• History of angioedema from any cause, including prior ACE inhibitor use 1, 3
• Pregnancy or women of childbearing potential without reliable contraception 1, 3
• Bilateral renal artery stenosis or stenosis in a solitary functioning kidney 1, 3
• Current use of aliskiren in patients with diabetes mellitus 1

Relative Contraindications/Cautions:

• Severe aortic stenosis (risk of hypotension) 1, 3
• Severe renal impairment (eGFR <30 mL/min/1.73m²) requires dose adjustment and close monitoring 1, 3
• Hyperkalemia (potassium >5.5 mEq/L) 1
• Concurrent use of potassium-sparing diuretics or potassium supplements without monitoring 1

Angiotensin Receptor Blockers (Losartan, Valsartan, Olmesartan, Telmisartan)

Absolute Contraindications:

• Pregnancy or women of childbearing potential without reliable contraception 1
• Bilateral renal artery stenosis or stenosis in a solitary functioning kidney 1
• Current use of aliskiren in patients with diabetes mellitus 1
• History of angioedema (though much rarer than with ACE inhibitors) 1

Relative Contraindications/Cautions:

• Severe renal impairment (eGFR <30 mL/min/1.73m²) requires dose adjustment 1
• Hyperkalemia (potassium >5.5 mEq/L) 1
• Severe hepatic impairment (particularly for losartan and valsartan, which undergo hepatic metabolism) 1

Calcium Channel Blockers—Dihydropyridines (Amlodipine, Nifedipine)

Absolute Contraindications:

• Severe aortic stenosis (risk of precipitating heart failure or syncope) 1
• Cardiogenic shock 1
• Known hypersensitivity to dihydropyridine calcium channel blockers 1

Relative Contraindications/Cautions:

• Severe left ventricular dysfunction or decompensated heart failure (though amlodipine has been studied in heart failure) 1
• Severe hypotension (systolic BP <90 mmHg) 1

Calcium Channel Blockers—Non-Dihydropyridines (Diltiazem, Verapamil)

Absolute Contraindications:

• Severe left ventricular systolic dysfunction (ejection fraction <40%) or decompensated heart failure 1
• Second- or third-degree atrioventricular block without a functioning pacemaker 1
• Sick sinus syndrome without a functioning pacemaker 1
• Atrial fibrillation or atrial flutter with accessory bypass tract (e.g., Wolff-Parkinson-White syndrome) 1
• Concurrent use with intravenous beta-blockers (risk of severe bradycardia or heart block) 1

Relative Contraindications/Cautions:

• Severe bradycardia (heart rate <50 bpm) 1
• Severe hepatic impairment (both drugs undergo extensive hepatic metabolism) 1

Beta-Blockers (Metoprolol, Atenolol, Carvedilol)

Note: Beta-blockers are not recommended as first-line therapy for uncomplicated hypertension unless compelling indications exist (prior myocardial infarction, heart failure with reduced ejection fraction, angina, atrial fibrillation requiring rate control) 1, 4

Absolute Contraindications:

• Severe bradycardia (heart rate <50 bpm) or second- or third-degree heart block without pacemaker 1
• Decompensated heart failure (for non-vasodilating beta-blockers) 1
• Severe asthma or chronic obstructive pulmonary disease with bronchospasm 1, 4
• Cardiogenic shock 1
• Sick sinus syndrome without pacemaker 1

Relative Contraindications/Cautions:

• Peripheral arterial disease with severe claudication 1
• Raynaud's phenomenon or severe peripheral vascular disease 1
• Diabetes mellitus with frequent hypoglycemic episodes (beta-blockers mask hypoglycemia symptoms) 1
• Metabolic syndrome or obesity (beta-blockers may worsen glucose and lipid metabolism) 1, 4

Critical Combination Contraindications

Never combine the following:

• ACE inhibitor + ARB (dual RAS blockade increases hyperkalemia and acute kidney injury risk without cardiovascular benefit) 1, 3
• ACE inhibitor or ARB + aliskiren in patients with diabetes or eGFR <60 mL/min/1.73m² 1
• Non-dihydropyridine calcium channel blocker + beta-blocker (risk of severe bradycardia, heart block, or heart failure) 1

Population-Specific Considerations

Black Patients:

• ACE inhibitors and ARBs are less effective as monotherapy; thiazide diuretics or calcium channel blockers are preferred first-line agents 1, 5

Elderly Patients (≥65 years):

• No specific contraindications, but start at lower doses and titrate carefully to avoid orthostatic hypotension 1
• Thiazide diuretics and calcium channel blockers are particularly effective 5

Chronic Kidney Disease:

• ACE inhibitors or ARBs are preferred when albuminuria is present 5
• Thiazide diuretics become less effective when eGFR <30 mL/min/1.73m²; loop diuretics should be used instead 1