Angiotensin II receptor blockers (sartans)
ATC code: C09CA01 (Losartan)
Selective AT1 angiotensin II receptor antagonist – blocks vasoconstriction, aldosterone secretion, sympathetic activation, and vascular smooth muscle proliferation. Unlike ACE inhibitors, it does not cause dry cough (no bradykinin accumulation). The active metabolite EXP3174 (formed via CYP2C9 and CYP3A4) provides most of the pharmacodynamic effect. Used in hypertension, HFrEF with ACE-inhibitor intolerance, and diabetic nephropathy.
First line
Losartan slows progression of diabetic nephropathy in type 2 diabetes. The RENAAL trial showed a 25 % reduction in doubling of creatinine and a 28 % reduction in end-stage renal disease. Monitor creatinine and potassium 1–2 weeks after initiation.
Diabetic nephropathy in type 2 diabetes patients.
First line
ARBs are an alternative to ACE inhibitors in HFrEF when ACEi are not tolerated due to cough. Mortality and hospitalization reduction is comparable to ACEi based on CHARM-Alternative (candesartan) and ELITE II (losartan) trials. Titration to maximum tolerated dose is mandatory.
Prescribed when ACE inhibitors are not tolerated (most commonly due to cough).
First line
Losartan is a first-line antihypertensive. Start at 50 mg once daily, maximum 100 mg. Prescribed as an alternative to ACE inhibitors, especially when ACEi-induced cough develops. The LIFE trial showed losartan superior to atenolol for stroke risk reduction in patients with hypertension and LVH.
8 pairs found. Sorted from critical to minor.
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. and the 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
Mechanism
Same as the ACE-inhibitor/spironolactone pair: the ARB blocks AT1 receptors and lowers aldosterone synthesis, while spironolactone blocks the mineralocorticoid receptor. Dual potassium-sparing action causes hyperkalemia, especially in older patients with CKD or diabetes.
Management
Justified in HFrEF ( 2024 guidelines). Start spironolactone at 12.5–25 mg. Monitor potassium and creatinine on the same schedule as for ACE inhibitors. If K+ exceeds 5.5 mmol/L, reduce the dose or discontinue.
Sources
Mechanism
Same as the aspirin/ACE-inhibitor pair: aspirin's NSAID effect blunts renal vasodilation, and patients with CKD or hypovolemia may develop acute kidney injury. Sartan antihypertensive effect is diminished. Antiplatelet aspirin doses of 75–100 mg barely affect renal prostaglandins. Analgesic and antipyretic doses of 500–1000 mg inhibit COX systemically and behave like other nonselective NSAIDs with respect to renal hemodynamics and BP.
Management
Antiplatelet aspirin doses of 75–100 mg are compatible – no adjustment needed. Analgesic and antipyretic doses of 500–1000 mg should be limited to the shortest possible course, with paracetamol preferred. In patients over 75 and/or with eGFR below 60 mL/min, analgesic-dose aspirin should be avoided. For NSAID courses longer than 5 days, check creatinine, potassium, and BP at 7–10 days ( Drug Safety Communication, July 2015).
Mechanism
Same as the ACE-inhibitor/furosemide pair: in a hypovolemic patient the first sartan dose can cause an abrupt BP drop and acute kidney injury. Chronic combination provides synergistic BP reduction.
Management
Assess volume status before starting losartan. Start at 25–50 mg at night. Check BP, creatinine, and potassium at 3–7 days. In older patients, start at 25 mg.
Sources
Mechanism
Synergistic BP reduction, a target combination in hypertension (losartan/hydrochlorothiazide fixed-dose product). In older patients with hypovolemia and RAAS activation, the first sartan dose can cause orthostatic hypotension and acute kidney injury.
Management
Start losartan at 25–50 mg (25 mg in older patients) and hydrochlorothiazide at 12.5 mg. Check BP with an orthostatic measurement, creatinine, potassium, and sodium at 7–14 days.
Sources
Mechanism
Synergistic BP reduction, a target hypertension combination. In older patients, symptomatic and orthostatic hypotension can occur.
Management
Start at low doses. Perform an orthostatic test at 1–2 weeks. BP goal in patients over 80 is 140/90 mmHg, not below 130/70.
Sources
Mechanism
Sartans, like ACE inhibitors, improve tissue insulin sensitivity. In patients on insulin or sulfonylureas with metformin, the risk of hypoglycemia rises modestly when losartan is started.
Management
Monitor glucose 1–2 weeks after losartan initiation. Be prepared to reduce insulin dose if applicable.
Sources
Mechanism
A target combination in HF and hypertension. Synergistic BP reduction. In older patients, symptomatic hypotension and bradycardia can occur. The sartan does not mask hypoglycemia (unlike the β-blocker, which can).
Management
Start at low doses. Check BP, heart rate, creatinine, and potassium at 1–2 weeks. In diabetic patients, remember that metoprolol masks tachycardia during hypoglycemia.
Sources
FDA category D. Drugs acting on the renin-angiotensin system cause fetal renal injury, oligohydramnios, pulmonary and skeletal hypoplasia. Discontinue when pregnancy is planned.
No data on excretion in breast milk. Not recommended during breastfeeding. Alternative antihypertensives are chosen if therapy is needed.
losartan is evaluated for the following indications with varying evidence strength: Hypertension (evidence tier A), Chronic kidney disease (evidence tier A), Heart failure (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of losartan (≥ 1 in 100): Dizziness, Hyperkalemia, Hypotension (more common with hypovolemia), Creatinine elevation. See the Safety section for uncommon and serious reactions.
FDA category D. FDA category D. Drugs acting on the renin-angiotensin system cause fetal renal injury, oligohydramnios, pulmonary and skeletal hypoplasia. Discontinue when pregnancy is planned.
No data on excretion in breast milk. Not recommended during breastfeeding. Alternative antihypertensives are chosen if therapy is needed.
losartan is contraindicated in: Pregnancy (all trimesters); Severe hyperkalemia; Bilateral renal artery stenosis or stenosis of a single functioning kidney; Concurrent aliskiren in patients with diabetes or CKD. Full list in the Safety section.