What antihypertensive medication can cause hyperkalemia?

Antihypertensive Medications That Cause Hyperkalemia

ACE inhibitors, angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) are the primary antihypertensive medications that cause hyperkalemia as a side effect. 1, 2

Primary Offending Agents

ACE Inhibitors and ARBs

• ACE inhibitors (such as lisinopril, enalapril, captopril) and ARBs both cause hyperkalemia by inhibiting the renin-angiotensin-aldosterone system, which reduces aldosterone-mediated potassium excretion in the kidney 1, 3
• These medications are first-line agents for hypertension in patients with diabetes and albuminuria, despite the hyperkalemia risk 1
• The FDA label for lisinopril explicitly warns that potassium-sparing diuretics can increase the risk of hyperkalemia when combined with ACE inhibitors 3
• Up to 10% of patients on ACE inhibitors or ARBs may experience at least mild hyperkalemia 4

Mineralocorticoid Receptor Antagonists

• MRAs (spironolactone, eplerenone, finerenone) carry significant hyperkalemia risk and are recommended for resistant hypertension when blood pressure remains ≥140/90 mmHg on three medications including a diuretic 1, 2
• Finerenone caused 2.3% discontinuation rates due to hyperkalemia in the FIDELIO-DKD trial, compared to 0.9% in placebo, though there were no deaths related to hyperkalemia 1
• Adding an MRA to a regimen already containing an ACE inhibitor or ARB substantially increases hyperkalemia risk, requiring vigilant monitoring 1

Potassium-Sparing Diuretics

• Potassium-sparing diuretics (amiloride, triamterene, spironolactone) directly reduce renal potassium excretion and increase hyperkalemia risk, particularly when combined with ACE inhibitors or ARBs 1, 3

Critical Risk Factors for Hyperkalemia

The following factors dramatically increase hyperkalemia risk and require more intensive monitoring:

• Chronic kidney disease, especially GFR <40 mL/min/1.73 m²: Risk increases 3.61-fold with GFR 31-40 and 6.81-fold with GFR <30 compared to GFR >50 5
• Diabetes mellitus: Increases susceptibility to hyperkalemia with RAAS inhibition 1, 6
• Combination therapy: Using both ACE inhibitors and ARBs together is contraindicated due to increased hyperkalemia, syncope, and acute kidney injury without added cardiovascular benefit 1
• Concomitant use of NSAIDs: Impairs renal potassium excretion and increases hyperkalemia risk 3, 7

Monitoring Requirements

Serum potassium and creatinine must be monitored at specific intervals to prevent life-threatening hyperkalemia:

• Within 1-2 weeks after initiating ACE inhibitor or ARB therapy 1
• Within 1-2 weeks after each dose increase 1
• At least annually during ongoing therapy 1
• More frequently (every 5-7 days initially) when adding MRAs, particularly in patients with reduced GFR 1
• Patients with GFR <60 mL/min/1.73 m² require more intensive monitoring due to substantially elevated risk 1

Important Clinical Caveats

• Dual RAAS blockade (ACE inhibitor + ARB, or either with direct renin inhibitor) is contraindicated due to lack of benefit and increased adverse events including hyperkalemia 1, 3
• Diuretic use (thiazide or loop) reduces hyperkalemia risk by 59% in patients on ACE inhibitors, making them valuable combination agents 5
• ACE inhibitors carry 7-fold higher hyperkalemia risk compared to calcium channel blockers and 2.85-fold higher risk compared to beta-blockers in patients with CKD 5
• Hyperkalemia increases mortality risk within 1 day of a hyperkalemic event, making prompt recognition and treatment essential 6
• Despite hyperkalemia risk, continuation of ACE inhibitors or ARBs as GFR declines to <30 mL/min/1.73 m² may provide cardiovascular benefit without significantly increasing end-stage kidney disease risk 1