Angiotensin receptor antagonists

Angiotensin receptor antagonists are used to treat hypertension, diabetic nephropathy and congestive heart failure. As a group these drugs are termed 'sartans', and this forms the stem of their non-proprietary names.

Clinical angiotensin receptor antagonists inhibit angiotensin II-induced activation of the AT₁ receptor, thereby modulating the renin–angiotensin system. This action leads to an inhibition of the effects mediated by angiotensin II, principally vasoconstriction and aldosterone and vasopressin secretion, which manifest clinically as decreased blood pressure and vascular resistance.

The efficacy of each sartan depends on its pressor inhibition (inhibition of the blood pressure-raising effect of angiotensin II), its AT₁ receptor affinity and its biological half-life.

Angiotensin receptor antagonists can be prescribed as single agents or in fixed-dose combinations with other antihypertensive agents, in particular with the thiazine diuretic hydrochlorothiazide.

All angiotensin receptor antagonists are contra-indicated with the direct renin inhibitor aliskiren, in patients with diabetes mellitus or who have kidney disease with an eGFR <60. All of these drugs should be avoided in patients with severe hepatic impairment and in pregnancy unless essential as they may adversely affect fetal and neonatal blood pressure control and renal function. Use with caution, in patients with renal impairment, starting with a low dose, and titrating according to response.

Single agent drugs:

Telmisartan: indicated for hypertension (20–40 mg once daily, titrating to 80mg if necessary), prevention of cardiovascular events in patients with established atherosclerotic cardiovascular disease, or diabetic organ damage (80mg once daily). Common side-effects include arthralgia, back pain, chest pain, eczema, gastro-intestinal disturbances, influenza-like symptoms, leg cramps, myalgia, pharyngitis, sinusitis and urinary-tract infection.

Olmesartan/Olmesartan medoxomil: Indicated for hypertension, starting at a daily dose of 10mg, increasing to 20mg if necessary. Maximum dose is 40mg/day. Contra-indicated in patients with biliary obstruction. Side-effects include arthritis, chest pain, cough, fatigue, gastro-intestinal disturbances, haematuria, hypertriglyceridaemia, hyperuricaemia, influenza-like symptoms, musculoskeletal pain, peripheral oedema, pharyngitis, rhinitis, and urinary-tract infection.

Valsartan: Indicated for hypertension, heart failure when ACE inhibitors cannot be used, or in conjunction with an ACE inhibitor when a beta-blocker cannot be used and myocardial infarction with left ventricular failure or left ventricular systolic dysfunction. Additional specific contra-indications arebiliary cirrhosis and cholestasis. Common side-effect is renal impairment.

Losartan: potassium: Indicated for hypertension, heart failure when ACE inhibitors cannot be used and diabetic nephropathy in type 2 diabetes mellitus. Additional specific contra-indication is for severe heart failure. Vertigo is a common side-effect. The manufacturer advises avoidance in patients with severe hepatic impairment

Irbesartan: Indicated in patients with hypertension, haemodialysis patients with hypertension and patients with type 2 diabetes renal disease. Common side-effects include fatigue, musculoskeletal pain, nausea and vomiting.

Azilsartan/azilsartan medoxomil: Indicated for hypertension and hypertension with intravascular volume depletion. Diarrhoea and raised creatine kinase levels are common side-effects. The manufacturer advises avoidance in patients with severe hepatic impairment, and low dose and close monitoring in patients with mild to moderate hepatic impairment.

Eprosartan: Indicated for hypertension, with an adult dose of 600mg once daily. Common side-effects include headache, nausea, rhinitis, diarrhoea, malaise and vomiting.

Candesartan/candesartan cilexetil: Indicated for hypertension (usual dose 8 mg once daily), hypertension with intravascular volume depletion (usual dose 8 mg once daily), heart failure with impaired left ventricular systolic function when ACE inhibitors are not tolerated and heart failure with impaired left ventricular systolic function in conjunction with an ACE inhibitor, under expert supervision (dosage starting at 4 mg once daily, increasing fortnightly to a target dose of 32 mg once daily or to the maximum tolerated dose). Contra-indicated in patients with cholestasis. In common with other sartans, common side-effects are headache and vertigo. Avoid prescribing in patients with severe hepatic impairment and use caution in renal impairment (eGFR less than 15).

Fixed-dose combination medicines:

Losartan with hydrochlorothiazide

Irbesartan with hydrochlorothiazide

Amlodipine with valsartan

Valsartan with hydrochlorothiazide

Olmesartan with amlodipine (a calcium-channel blocker)

Telmisartan with hydrochlorothiazide

Olmesartan with hydrochlorothiazide

Olmesartan with amlodipine and hydrochlorothiazide