Can losartan (angiotensin‑II receptor blocker) be co‑administered with captopril (ACE inhibitor) in an adult patient with hypertension or heart failure?

Co-Administration of Losartan and Captopril: Not Recommended

Do not combine losartan (an ARB) with captopril (an ACE inhibitor) in the same patient, as this dual renin-angiotensin system blockade increases the risk of hyperkalemia, syncope, and acute kidney injury by 2–3-fold without providing additional cardiovascular benefit. 1, 2

Evidence Against Combination Therapy

Major Trial Data

• The VALIANT trial directly tested the combination of valsartan (an ARB) plus captopril versus either drug alone in post-myocardial infarction patients with heart failure or left ventricular dysfunction. 1
• The combination arm showed no increased efficacy over captopril alone but had a higher incidence of discontinuation due to adverse effects, including hypotension, renal dysfunction, and hyperkalemia. 1
• The lack of superiority was attributed to aggressive simultaneous titration of both agents in the early post-MI period, which resulted in more side effects without added benefit. 1

Guideline Consensus

• The American College of Cardiology/American Heart Association issues a Class III: Harm recommendation against combining an ARB with an ACE inhibitor, stating this combination raises rates of hyperkalemia, syncope, and acute kidney injury without improving cardiovascular outcomes. 2
• The FDA drug label for losartan does not list combination with ACE inhibitors as an approved regimen, and current hypertension guidelines explicitly advise against dual RAAS blockade. 3
• Multiple guideline sources from 2024-2026 consistently warn that combining losartan with ACE inhibitors or direct renin inhibitors is contraindicated due to substantially increased adverse event risk. 2, 4

When Combination Was Considered (Historical Context)

• The CHARM-Added trial showed that in patients with stable heart failure already on established ACE inhibitor therapy, adding the ARB candesartan was well tolerated and reduced hospitalizations. 1
• This differs from VALIANT because CHARM enrolled stable chronic heart failure patients (not acute post-MI), used gradual titration, and added the ARB to an already-optimized ACE inhibitor dose rather than titrating both simultaneously. 1
• However, even this strategy is no longer recommended by current guidelines, which prioritize single-agent RAAS blockade combined with other drug classes (diuretics, beta-blockers, mineralocorticoid receptor antagonists) over dual RAAS blockade. 2

Correct Approach to Inadequate Response

If Blood Pressure Remains Uncontrolled on Losartan Alone

• Increase losartan to the maximum dose of 100 mg once daily before adding other agents. 2
• Add hydrochlorothiazide 12.5–25 mg once daily as the preferred second agent; this combination provides additive blood pressure lowering (approximately 15.5/9.2 mmHg additional reduction). 2, 3
• If triple therapy is needed, add a dihydropyridine calcium channel blocker (e.g., amlodipine 5–10 mg daily) to create the preferred ARB + thiazide + CCB regimen. 2

If Patient Cannot Tolerate Losartan

• Switch to captopril (or another ACE inhibitor) rather than combining the two drugs. 2
• The ELITE-II trial showed that losartan 50 mg daily and captopril 150 mg daily had similar efficacy and mortality rates in heart failure patients, confirming they are therapeutic alternatives, not complementary agents. 1, 5

For Heart Failure with Reduced Ejection Fraction

• Use either an ACE inhibitor or an ARB as monotherapy, not both. 2
• If the patient is already on an ACE inhibitor and requires additional neurohormonal blockade, add a mineralocorticoid receptor antagonist (spironolactone 25 mg daily or eplerenone) rather than an ARB. 1, 2
• Spironolactone added to ACE inhibitor + diuretic therapy prevents 5–6 deaths per year per 100 patients in severe heart failure, a benefit not seen with dual RAAS blockade. 5

Critical Safety Monitoring If Combination Is Mistakenly Prescribed

• Check serum creatinine/eGFR and potassium within 1–2 weeks of starting the combination. 2
• Discontinue one agent immediately if potassium exceeds 5.5 mEq/L or if creatinine rises more than 30% from baseline. 2, 6
• Monitor for symptomatic hypotension (mean arterial pressure < 65 mmHg), which is more common with dual blockade. 6

Common Pitfall to Avoid

• Do not assume that blocking the renin-angiotensin system at two points provides "more complete" blockade—the VALIANT and other trials definitively showed this strategy increases harm without added benefit. 1, 2
• Recognize that both drugs work on the same pathway (preventing angiotensin II effects), so their adverse effects (hyperkalemia, renal dysfunction, hypotension) are additive rather than complementary. 1, 5