Major
Enalapril × Losartan
Angiotensin-converting enzyme inhibitors (ACEi)×Angiotensin II receptor blockers (sartans)
Mechanism
Dual RAAS blockade: ACE-I blocks angiotensin II formation, ARB blocks its receptors. Additive risk of hyperkalaemia, hypotension, and acute kidney injury without additional clinical benefit.
Symptoms
Weakness, dizziness on standing, syncope. Reduced urine output, rising serum creatinine. Weakness and paraesthesia from hyperkalaemia. Symptoms typically appear in the first 1–4 weeks.
Management
The combination is not prescribed. Large trials (ONTARGET, ALTITUDE) showed no benefit and more adverse effects. Choose one agent: ACE-I if tolerated, ARB if there is a dry cough or intolerance.
Sources
- 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
- 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
- KDIGO: KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)– Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 2024;105(4S):S117-S314.