What are the contraindications for Angiotensin (Angiotensin) Receptor Blockers (ARBs)?

Contraindications for Angiotensin Receptor Blockers (ARBs)

ARBs are absolutely contraindicated in patients with a history of angioedema, pregnancy, bilateral renal artery stenosis (or unilateral stenosis with a solitary kidney), and hypersensitivity to any component of the drug. 1, 2

Absolute Contraindications

• Pregnancy: ARBs must be avoided in pregnancy due to teratogenic effects 1
• History of angioedema: While angioedema is less common with ARBs than ACE inhibitors, patients who developed angioedema on an ACE inhibitor may also develop it with an ARB, and caution is strongly advised 3, 1
• Bilateral renal artery stenosis or unilateral stenosis in a solitary kidney: ARBs can precipitate acute kidney injury in these patients 3, 1
• Hypersensitivity: Known hypersensitivity to any component of the ARB formulation 2
• Coadministration with aliskiren in diabetic patients: This combination is explicitly contraindicated due to increased risks of hyperkalemia, renal dysfunction, and hypotension without additional benefit 2, 4

Relative Contraindications and High-Risk Situations

• Hypotension: Do not initiate ARBs in patients with systolic blood pressure <80 mmHg or those at immediate risk of cardiogenic shock until hemodynamically stabilized 3, 1
• Severe renal impairment: Use with extreme caution when serum creatinine is >3 mg/dL or >250 μmol/L, or in patients with worsening renal function from prior ACEI/ARB exposure 3, 1, 5
• Hyperkalemia: Do not initiate if serum potassium is >5.0-5.5 mEq/L until corrected 1, 5
• Shock: ARBs are contraindicated in patients presenting with shock 3

Critical Drug Interactions and Combination Therapy Warnings

The routine combination of an ARB with both an ACE inhibitor AND an aldosterone antagonist (triple RAS blockade) is potentially harmful and should be avoided. 3, 1, 6

• Dual RAS blockade: Combining ARBs with ACE inhibitors or aliskiren increases risks of hypotension, hyperkalemia, and acute renal failure without providing additional cardiovascular benefit in most patients 6, 2, 4
• Potassium-raising agents: Coadministration with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium supplements, salt substitutes, or heparin significantly increases hyperkalemia risk 2, 4
• NSAIDs: In elderly, volume-depleted, or renally compromised patients, NSAIDs (including COX-2 inhibitors) combined with ARBs may cause acute renal failure and attenuate antihypertensive effects 2, 4
• Lithium: ARBs can increase serum lithium levels and precipitate lithium toxicity; monitor lithium levels closely 2, 4
• Aliskiren in renal impairment: Avoid combining ARBs with aliskiren in patients with GFR <60 mL/min 2, 4

Mandatory Monitoring Protocol

Before initiating ARB therapy, obtain baseline blood pressure, serum creatinine, and serum potassium. 1

• Early monitoring: Reassess blood pressure (including postural changes), renal function, and potassium within 1-2 weeks after initiation and after each dose increase 3, 1, 5
• High-risk patients: Those with diabetes, pre-existing renal dysfunction, low serum sodium, or systolic BP <80 mmHg require particularly close surveillance 3, 1
• Combination therapy: When ARBs are used with aldosterone antagonists, more vigilant monitoring of potassium and renal function is essential 1

Common Clinical Pitfalls to Avoid

• Do not add an ARB to a patient already on adequate-dose ACE inhibitor therapy: This provides no additional mortality benefit and substantially increases adverse event risk 5, 6
• Do not continue ARBs if significant adverse effects develop: Discontinue immediately if persistent hyperkalemia or progressive renal dysfunction occurs 1
• Do not use ARBs as add-on therapy in patients already taking an ARNI (angiotensin receptor-neprilysin inhibitor): ARBs are already a component of ARNI regimens, and adding another ARB or ACE inhibitor increases risk of angioedema, hypotension, and renal insufficiency 3