Critical
enalapril × losartan
Angiotensin-converting enzyme inhibitors (ACEi)×Angiotensin II receptor blockers (sartans)
Mechanism
Dual RAAS blockade at two levels: enalapril blocks angiotensin II formation, losartan blocks the binding of residual angiotensin II to the AT1 receptor. The ONTARGET (2008) and ALTITUDE (2012) trials showed no added mortality benefit and increased risks of hyperkalemia, hypotension, and acute kidney injury. ESC and the FDA recommend avoiding the combination.
Management
Do not combine an ACE inhibitor with an ARB. If a patient has ACE-inhibitor cough, switch to an ARB. If stronger RAAS blockade is needed, add a mineralocorticoid receptor antagonist (with potassium monitoring) rather than a second RAAS blocker.
Sources
- ONTARGET Investigators: Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events (2008)— N Engl J Med 2008;358(15):1547–1559
- ALTITUDE Investigators: Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes (2012)— N Engl J Med 2012;367(23):2204–2213
- ESC: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure (2021)— Eur Heart J 2021;42(36):3599–3726
- ESC: 2024 ESC Guidelines for the management of elevated blood pressure and hypertension (2024)— Eur Heart J 2024;45(38):3912–4018