ramipril and losartan

Additive pharmacodynamic effect on the renin-angiotensin-aldosterone system (RAAS). Ramipril inhibits angiotensin-converting enzyme, reducing angiotensin II formation. Losartan blocks angiotensin II at the AT1 receptor. The combined effect further reduces aldosterone secretion, leading to increased potassium retention and vasodilation. This additive action on the RAAS can potentiate the hypotensive and hyperkalaemic effects, and also reduce renal perfusion.

Combining ramipril and losartan increases the risk of hyperkalaemia, hypotension, and acute kidney injury, particularly in patients with pre-existing renal impairment, volume depletion, or diabetes. The risk of adverse outcomes is higher than with either agent alone. Some patient groups, such as those with heart failure, might be considered for combination therapy under specialist supervision, but the evidence for added benefit is limited and not consistently demonstrated.

Avoid the combination unless there is a compelling indication and specialist input. If used, initiate with close monitoring of serum potassium, creatinine, and blood pressure at baseline, then within 1 to 2 weeks of starting or dose adjustment, and periodically thereafter. Discontinue one agent if hyperkalaemia, significant hypotension, or worsening renal function occurs. Due to the lack of clear benefit for most indications, this combination is not recommended routinely.

Well established through multiple randomised trials and meta-analyses. Guidelines, including those for hypertension and heart failure, generally advise against routine dual RAAS blockade. Practice may vary in selected patient groups, but the interaction is widely recognised.