Is an Angiotensin Receptor Blocker (ARB) preferred over an Angiotensin-Converting Enzyme Inhibitor (ACEI) in patients with diabetes and/or Chronic Kidney Disease (CKD)?

ARB vs ACE Inhibitor in Diabetes and CKD

Neither ARBs nor ACE inhibitors are preferred over the other—they are clinically equivalent for kidney and cardiovascular protection in patients with diabetes and/or CKD. 1 The choice between these agents should be based on tolerability, cost, and availability rather than efficacy differences.

Evidence for Clinical Equivalency

The KDIGO 2020 guidelines explicitly state that evidence does not demonstrate superior efficacy of ACE inhibitors over ARB treatment or vice versa. 1 Both drug classes:

• Reduce progression to end-stage renal disease by 16-29% in patients with diabetic kidney disease 2
• Slow doubling of serum creatinine with moderate quality evidence 1
• Decrease albuminuria progression comparably 1
• Should be titrated to the maximum tolerated dose for optimal kidney protection 1

When to Choose ARB Over ACE Inhibitor

Switch to an ARB if ACE inhibitor-induced cough develops, which affects approximately 10% of patients. 1 This is the primary clinical reason to prefer ARBs, as:

• ARBs have significantly lower incidence of cough compared to ACE inhibitors 3
• The incidence of angioedema with ARBs (0.11%) is not significantly different from placebo (0.07%) 1
• ARBs may produce a smaller magnitude of potassium rise compared to ACE inhibitors 2

Specific Recommendations by Diabetes Type

Type 1 Diabetes with Albuminuria

• ACE inhibitors are first-line based on established evidence from the Collaborative Study Group trial 2
• ARBs are an acceptable alternative if ACE inhibitors are not tolerated 1

Type 2 Diabetes with Macroalbuminuria (≥300 mg/g)

• Either ACE inhibitors or ARBs are equally effective first-line options 2
• Head-to-head comparisons demonstrate clinical equivalency 1
• Losartan and irbesartan have the strongest renal outcome evidence with FDA approval for diabetic nephropathy 4

Implementation Algorithm

1. Initiate either ACE inhibitor or ARB in patients with diabetes, hypertension, and albuminuria (>30 mg/g) 1

2. Start at low dose and titrate to maximum approved dose that the patient tolerates 1

3. Monitor within 2-4 weeks of initiation or dose change:

   • Serum creatinine (continue unless >30% increase) 1
   • Serum potassium 1
   • Blood pressure 1

4. Switch from ACE inhibitor to ARB only if:

   • Persistent cough develops 1
   • Angioedema occurs (rare but serious) 1

5. Add SGLT2 inhibitor regardless of which RAS blocker is chosen for enhanced kidney and cardiovascular protection 1, 5

Critical Contraindications

Never combine ACE inhibitors with ARBs in patients with diabetes and CKD. 1, 6 The VA NEPHRON-D trial definitively showed that dual RAS blockade:

• Provides no additional benefit for kidney outcomes 6
• Increases hyperkalemia risk (RR 2.07) 7
• Increases acute kidney injury risk 6
• Increases hypotension risk (RR 2.19-3.95) 7

Discontinue ACE inhibitors or ARBs in women considering pregnancy or who become pregnant due to fetal toxicity including oligohydramnios, lung hypoplasia, and skeletal deformations. 1, 4

Managing Side Effects Without Discontinuation

Hyperkalemia (K+ >5.0 mEq/L)

• Recheck elevated potassium before making therapeutic changes 1
• Moderate dietary potassium intake 1
• Consider diuretics 1
• Use sodium bicarbonate if metabolic acidosis present 1
• Consider gastrointestinal cation exchangers 1
• Consider potassium binders to facilitate ongoing therapy 1
• Reduce dose or stop as last resort only 1

Acute eGFR Decline

• Tolerate acute eGFR decreases ≤30% after initiation—do not discontinue prematurely 1
• If >30% decline: ensure euvolemia, discontinue nephrotoxic agents (NSAIDs), evaluate alternative etiologies including renal artery stenosis 1

Comparative Research Evidence

Recent network meta-analysis of 44 trials with 42,319 patients showed ACE inhibitors had the highest probability rankings for kidney protection (SUCRA 93.3%), cardiovascular death prevention (SUCRA 86%), and all-cause mortality reduction (SUCRA 94.1%) compared to other antihypertensives. 3 However, a 2019 cohort study of 1,120 CKD patients found no significant differences between ACE inhibitors and ARBs regarding progression to ESRD (HR 1.31,95% CI 0.37-4.66). 8 A 2024 Cochrane review concluded that ARBs versus ACE inhibitors had uncertain effects on all-cause death, kidney failure, and doubling of serum creatinine due to low certainty evidence. 9

Dosing for Maximum Renoprotection

Losartan (if ARB chosen): Start 50 mg daily, titrate to 100 mg daily with dose-dependent renoprotective effect 4

Irbesartan (if ARB chosen): Use 150-300 mg daily based on clinical response 4

ACE inhibitors: Titrate to highest approved dose tolerated per individual agent prescribing information 1

Additional Considerations

• Generic formulations of both ACE inhibitors and ARBs are widely available at low cost and included in WHO essential medicines list 1
• Most patients require 2-3 antihypertensive agents to reach target blood pressure <130/80 mmHg 1, 2
• 60-90% of patients in major ARB trials used concomitant diuretics 4
• Both drug classes require monitoring but neither should be discontinued in patients on dialysis 1