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

Contraindications of Angiotensin Receptor Blockers (ARBs)

ARBs are absolutely contraindicated in pregnancy, bilateral renal artery stenosis (or unilateral stenosis with a solitary kidney), and in patients with a history of angioedema, though angioedema risk is lower than with ACE inhibitors. 1, 2

Absolute Contraindications

• Pregnancy: ARBs are classified as category C/D and contraindicated throughout pregnancy due to fetal toxicity including renal dysplasia, oligohydramnios, growth retardation, skull ossification disorders, lung hypoplasia, and intrauterine death 1, 2

• Bilateral renal artery stenosis or unilateral stenosis in a solitary kidney: ARBs cause preferential efferent arteriolar vasodilation, leading to acute kidney injury and potentially severe renal failure in these patients 1, 2, 3, 4, 5

• History of angioedema: While less common than with ACE inhibitors, angioedema can occur with ARBs, and caution is warranted especially in patients who developed angioedema to ACE inhibitors 1, 2

Relative Contraindications and High-Risk Situations

• Severe hypotension: Patients with systolic blood pressure <80 mmHg or those at immediate risk of cardiogenic shock should not receive ARBs until hemodynamically stabilized 1, 2

• Hyperkalemia: Serum potassium >5.5 mEq/L is a relative contraindication; ARBs should be used with extreme caution and close monitoring 1, 2

• Advanced renal dysfunction: Markedly elevated serum creatinine (>3 mg/dL or >220 μmol/L) or worsening renal function with previous renin-angiotensin system blockade warrants caution 1, 2

Critical Monitoring Requirements

Before initiating ARB therapy, assess baseline blood pressure (including orthostatic measurements), serum creatinine, and potassium levels 1, 2

Within 1-2 weeks of initiation or dose changes, reassess:

• Blood pressure and postural changes
• Renal function (serum creatinine)
• Serum potassium 1, 2

Patients requiring particularly vigilant surveillance include those with:

• Systolic blood pressure <80 mmHg
• Low serum sodium
• Diabetes mellitus
• Pre-existing renal impairment 1, 2

Special Clinical Scenarios

Triple renin-angiotensin system blockade (ARB + ACE inhibitor + aldosterone antagonist) is potentially harmful and not recommended due to significantly increased risks of hyperkalemia and renal dysfunction 1, 2

Combination ARB + ACE inhibitor therapy showed no mortality benefit and increased side effects in post-MI patients, though modest reductions in hospitalization were seen in heart failure patients 1

In heart failure with reduced ejection fraction (<40%), ARBs are recommended as an alternative when ACE inhibitors are not tolerated, but the combination of both does not improve outcomes and increases adverse events 1

Common Pitfalls to Avoid

• Do not assume ARBs are safe in bilateral renal artery stenosis even after successful revascularization without careful monitoring, though some data suggest safety post-stenting 6

• Do not use ARBs as first-line therapy in unilateral renal artery stenosis with two functioning kidneys; diuretics, beta-blockers, and calcium channel blockers are preferred 3

• Do not overlook women of childbearing potential: ARBs must be discontinued before conception or immediately upon pregnancy recognition 1

• Do not ignore incremental creatinine rises: A rise to >310 μmol/L (3.5 mg/dL) mandates immediate discontinuation 1