Can a Patient Switch Back to an ACE Inhibitor?
Yes, a patient can attempt switching back to an ACE inhibitor if there is a compelling clinical reason, but only after the initial cough has completely resolved (typically 1-4 weeks, occasionally up to 3 months after discontinuation), and this rechallenge carries Grade A evidence support. 1
Primary Consideration: ACE Inhibitor-Induced Cough
The most common reason for ACE inhibitor discontinuation is cough, which occurs through bradykinin and substance P accumulation. 1 The key question is whether the patient previously discontinued the ACE inhibitor due to cough or angioedema, as these determine completely different management pathways.
If Previous Discontinuation Was Due to Cough:
A repeat trial of ACE inhibitor therapy may be attempted if there is a compelling clinical indication (such as heart failure with reduced ejection fraction, post-MI with LVEF ≤40%, diabetes, chronic kidney disease, or hypertension). 1
Wait for complete cough resolution before rechallenge, which typically occurs within 1-4 weeks but may take up to 3 months in some patients. 1
The cough may or may not recur upon rechallenge—this is an empirical trial with substantial net benefit according to ACCP guidelines. 1
If cough recurs and is intolerable, switch definitively to an ARB, which has similar efficacy but significantly lower cough incidence (comparable to placebo/hydrochlorothiazide). 1
If Previous Discontinuation Was Due to Angioedema:
Absolutely contraindicated—never rechallenge with any ACE inhibitor for life. 2, 3
ACE inhibitor-induced angioedema is an absolute contraindication to all ACE inhibitors permanently. 2
ARBs may be considered as an alternative, but only after a mandatory 6-week washout period from ACE inhibitor discontinuation. 4, 5
ARBs carry a much lower (but not zero) risk of cross-reactivity angioedema, making them reasonable alternatives when RAAS blockade is clinically necessary. 1, 4
Neprilysin inhibitors (ARNIs like sacubitril/valsartan) are absolutely contraindicated in any patient with prior angioedema history and require a 36-hour washout when switching from ACE inhibitors. 3
Clinical Scenarios Where ACE Inhibitor Rechallenge Is Most Justified:
Compelling indications for ACE inhibitor therapy include: 1
- Heart failure with LVEF ≤40% (Class I, Level A recommendation) 1
- Post-myocardial infarction with LV dysfunction 1
- Chronic kidney disease 1
- Diabetes mellitus 1
- Hypertension requiring RAAS blockade 1
In these populations, the mortality and morbidity benefits of ACE inhibitors are substantial and well-established. 1
Alternative Management If Rechallenge Fails:
If the patient cannot tolerate ACE inhibitor rechallenge due to recurrent cough:
First-line alternative: Switch to an ARB (losartan, valsartan, telmisartan, etc.), which provides equivalent cardiovascular outcomes with significantly fewer adverse effects. 1, 6
Consider pharmacologic cough suppression if ACE inhibitor continuation is absolutely necessary: sodium cromoglycate, theophylline, sulindac, indomethacin, nifedipine, ferrous sulfate, or picotamide (Grade B recommendation, though this is rarely practical in clinical practice). 1
Critical Safety Monitoring:
When reinitiating ACE inhibitor therapy: 1
Check serum creatinine and potassium at baseline and 1 week after initiation. 1
Acceptable creatinine rise: ≤0.5 mg/dL if baseline creatinine is <2.0 mg/dL, or ≤1.0 mg/dL if baseline creatinine is ≥2.0 mg/dL. 1
Progressive creatinine elevation beyond these thresholds warrants discontinuation and evaluation for renovascular disease. 1
ACE inhibitor-associated acute renal failure is almost always reversible within 2-3 days of discontinuation. 1
Common Pitfall to Avoid:
Do not confuse "switching back" with "switching from." If the patient is currently on an ARNI (sacubitril/valsartan), switching to an ACE inhibitor requires a mandatory 36-hour washout period to avoid life-threatening angioedema from dual bradykinin pathway inhibition. 3 This is an FDA-mandated contraindication with no exceptions. 3