Can we measure the aldosterone-to-renin ratio (ARR) in a patient taking metoprolol (beta-blocker)?

Can ARR Testing Be Performed While on Metoprolol?

Yes, ARR testing can be performed while a patient is on metoprolol, but you must interpret results knowing that beta-blockers significantly increase the ARR by suppressing renin, which raises the risk of false-positive results rather than false-negatives. 1, 2

Understanding the Effect of Beta-Blockers on ARR

• Metoprolol and other beta-blockers suppress renin secretion, causing the ARR to increase by approximately 62% from baseline 2
• This suppression of renin elevates the ratio even when aldosterone levels remain unchanged, creating potential false-positive screening results 1, 3
• Importantly, beta-blockers do not cause false-negative results—they will not mask true primary aldosteronism 4

When to Test on Metoprolol vs. When to Switch

Ideally, discontinue metoprolol when clinically feasible and substitute with non-interfering antihypertensives at least 2 weeks before testing 1, 2:

• Safe alternatives to use during ARR testing:
  • Long-acting calcium channel blockers (verapamil slow-release, amlodipine) 1, 2
  • Alpha-receptor antagonists (prazosin, doxazosin) 1, 2
  • Hydralazine 1

However, if blood pressure control is inadequate with non-interfering agents alone, or if discontinuing metoprolol poses clinical risk, proceed with testing while the patient remains on metoprolol 1, 5:

• The American Heart Association and American College of Cardiology recommend testing patients on their current medications and interpreting results in context when medication discontinuation is not feasible 1
• One study of 90 patients demonstrated that ARR screening without discontinuing antihypertensive medications (including beta-blockers) successfully identified all cases of primary aldosteronism without false-negatives 5

Practical Testing Algorithm While on Metoprolol

1. Ensure proper patient preparation 1:

   • Correct hypokalemia (target 4.0-5.0 mEq/L) as it suppresses aldosterone production 1
   • Liberal salt intake for at least 3 days before testing 1
   • Collect blood mid-morning after patient has been upright for 2 hours and seated for 5-15 minutes 1

2. Interpret ARR with adjusted threshold 1, 3:

   • Standard positive ARR: ≥20-30 (ng/dL)/(ng/mL/h) with plasma aldosterone ≥10-15 ng/dL 1
   • On beta-blockers, expect the ratio to be artificially elevated by ~62% 2, 3
   • If ARR is borderline or mildly elevated (20-50), consider this may represent a false-positive from beta-blocker effect 3
   • If ARR is markedly elevated (>50-100), this likely represents true primary aldosteronism despite beta-blocker use 4, 5

3. Confirmatory testing is mandatory regardless 1:

   • All positive ARR results require confirmatory testing (IV saline suppression test or oral sodium loading) to demonstrate autonomous aldosterone secretion 1
   • For confirmatory testing, mineralocorticoid receptor antagonists must be withdrawn at least 4 weeks beforehand, but beta-blockers can continue if necessary 6, 1

Key Clinical Pitfall to Avoid

• Do not dismiss an elevated ARR as "just the beta-blocker" without confirmatory testing 1, 4
• While beta-blockers increase false-positives, they do not cause false-negatives—a truly elevated ARR on metoprolol still warrants full diagnostic workup 4, 5
• The European Society of Cardiology emphasizes that if medications cannot be safely discontinued, testing should proceed with careful interpretation rather than being deferred indefinitely 6, 1