Duration for Stopping ACEIs/ARBs Before ARR Testing
ACE inhibitors and ARBs should be discontinued for at least 2 weeks before aldosterone-to-renin ratio (ARR) testing to prevent false-negative results. 1
Rationale for Medication Withdrawal
ACEIs and ARBs significantly interfere with the renin-angiotensin-aldosterone system (RAAS), causing increased renin levels and decreased aldosterone levels, which can mask primary aldosteronism. 1
The American College of Cardiology explicitly states that these medications must be withdrawn for at least 2 weeks prior to testing to avoid false negatives. 1
Research confirms that ACEIs and ARBs are among the most important interfering medications, with studies showing they can produce false-negative results by stimulating renin secretion. 2
Optimal Testing Conditions
Beyond stopping ACEIs/ARBs, several additional factors optimize ARR accuracy:
Patients should maintain unrestricted (liberal) salt intake during the testing period, as dietary salt restriction can falsely stimulate renin and lower the ARR. 1, 2
Serum potassium must be corrected to normal range before testing, as hypokalemia suppresses aldosterone production and can cause false-negative results. 1, 2
Blood should be collected mid-morning from seated patients following 2-4 hours of upright posture to improve test sensitivity. 2
Management of Other Interfering Medications
Diuretics (including spironolactone and eplerenone) require a longer withdrawal period of at least 4 weeks before ARR testing, as they significantly alter the ratio. 1
Beta-blockers, alpha-methyldopa, and clonidine suppress renin and can cause false-positive results; ideally these should be stopped at least 2 weeks before testing. 2
Where blood pressure control is necessary during the washout period, substitute with non-interfering agents such as verapamil slow-release combined with hydralazine, prazosin, or doxazosin. 2
Important Caveats
The ARR is a screening test only and should be repeated at least once before proceeding to confirmatory suppression testing, as reproducibility can be poor with up to five-fold variation between measurements taken under identical conditions. 2, 3
Recent research suggests that in some clinical contexts, initial screening may be performed without medication withdrawal, but this approach has significantly lower sensitivity (22.2%) and should not replace the standard approach when feasible. 4, 3
Monitor for rebound hypokalemia when withdrawing mineralocorticoid receptor antagonists, especially in patients who may have undiagnosed primary aldosteronism. 1