What is the recommended approach when switching from an Angiotensin-Converting Enzyme (ACE) inhibitor to an Angiotensin Receptor Blocker (ARB)?

Switching from an ACE Inhibitor to an ARB

When switching from an ACE inhibitor to an ARB in patients with heart failure or CKD, you can transition directly without a washout period—simply stop the ACE inhibitor and start the ARB the next day, monitoring blood pressure, serum creatinine, and potassium within 2-4 weeks. 1

Direct Transition Without Washout

• No washout period is required when switching from an ACE inhibitor to a standard ARB (unlike the mandatory 36-hour washout required when switching to an ARNI) 2
• Stop the ACE inhibitor and initiate the ARB on the following day 1
• This direct switch is safe and effective, as demonstrated in the CORD IA trial involving over 4,000 patients who discontinued ACE inhibitors and immediately switched to losartan with excellent safety outcomes 3

Indications for Switching

The primary reasons to switch from an ACE inhibitor to an ARB include:

• Persistent dry cough (occurs in up to 20% of ACE inhibitor users, 8 times more frequent than with ARBs) 1, 3
• History of angioedema with ACE inhibitor (though caution is warranted as 2-17% cross-reactivity exists—some patients develop angioedema with ARBs as well) 1, 2
• Intolerance to ACE inhibitors for other reasons while maintaining renin-angiotensin system blockade 1

Starting Dose and Titration Strategy

• Begin with low doses of the ARB and titrate upward to target doses proven effective in clinical trials 1
• Target doses should match those used in landmark trials that demonstrated cardiovascular and renal benefits 1
• If target doses are not tolerated, intermediate doses should be maintained rather than discontinuing therapy entirely 1
• Evidence suggests that higher doses of ARBs significantly reduce heart failure hospitalization (2.8% absolute risk reduction) and heart failure worsening (3.2% absolute risk reduction) compared to lower doses 4

Critical Monitoring Parameters

Within 2-4 weeks of initiating or increasing ARB dose, assess the following 1:

• Blood pressure (including orthostatic measurements)—watch for symptomatic hypotension 1
• Serum creatinine—continue ARB unless creatinine rises >30% within 4 weeks 1
• Serum potassium—manage hyperkalemia with potassium-lowering measures rather than immediately stopping the ARB 1

Managing Common Side Effects

Hyperkalemia

• First-line approach: Implement measures to reduce serum potassium (dietary restriction, potassium binders, diuretic adjustment) rather than decreasing or stopping the ARB 1
• Only reduce dose or discontinue if hyperkalemia remains uncontrolled despite medical management 1

Creatinine Elevation

• Accept up to 30% increase in serum creatinine within 4 weeks as an expected hemodynamic effect 1
• If creatinine rises >30%, evaluate for acute kidney injury, volume depletion, renal artery stenosis, and concomitant nephrotoxic medications (NSAIDs) 1
• Consider dose reduction or discontinuation only if elevation exceeds 30% and other causes are excluded 1

Hypotension

• Optimize volume status before initiating ARB to minimize hypotension risk 1
• Consider empiric modest reduction in loop diuretic dose in non-congested patients with borderline blood pressure (systolic BP ≤100 mmHg) 1
• Reduce dose or discontinue only if symptomatic hypotension occurs despite volume optimization 1

Important Contraindications and Cautions

Absolute contraindications 1:

• Pregnancy or women planning to become pregnant (advise contraception and discontinue immediately if pregnancy occurs) 1
• Known hypersensitivity to ARBs 1
• Concomitant use with another ACE inhibitor or direct renin inhibitor (dual RAS blockade is harmful) 1

Use with caution in 1:

• Systolic blood pressure <100 mmHg 1
• Renal insufficiency or bilateral renal artery stenosis 1
• Baseline potassium >5.0 mEq/L 1
• Volume depletion 1

Special Populations

Chronic Kidney Disease

• Continue ARB even when eGFR falls below 30 mL/min/1.73 m² unless symptomatic hypotension, uncontrolled hyperkalemia, or uremic symptoms develop 1
• ARBs are recommended for patients with CKD and moderately-to-severely increased albuminuria (A2-A3) with or without diabetes 1

Heart Failure with Reduced Ejection Fraction

• ARBs reduce mortality and heart failure hospitalizations in patients with HFrEF who are intolerant to ACE inhibitors 1
• For patients tolerating ACE inhibitors, consider switching to an ARNI (with mandatory 36-hour washout) rather than a standard ARB for superior outcomes 1
• ARBs remain appropriate for patients in whom ARNI is not suitable 1

Common Pitfalls to Avoid

• Do not combine ACE inhibitor with ARB—dual RAS blockade increases adverse events without additional benefit in most populations 1, 5
• Do not discontinue prematurely for minor creatinine elevations (<30%) or manageable hyperkalemia 1
• Do not confuse ARB switch with ARNI switch—ARNIs require a 36-hour washout from ACE inhibitors to prevent life-threatening angioedema, but standard ARBs do not 2
• Do not underdose—titrate to target doses used in clinical trials to achieve proven benefits 1, 4