Valsartan

Angiotensin II receptor blockers (ARBs)

ATC code: C09CA03 (Valsartan)

Mechanism of action

Selective AT1 angiotensin II receptor antagonist. Blocks vasoconstriction, aldosterone secretion, and proliferative effects of angiotensin II. Does not cause dry cough, unlike ACE inhibitors, because it does not affect bradykinin degradation. Half-life is about 6 hours, but the clinical effect lasts 24 hours.

Indications

Heart failure

First line

Valsartan is a proven ACE inhibitor alternative in HFrEF. The Val-HeFT trial showed a 27% reduction in hospitalizations when valsartan was added to background therapy. Sacubitril/valsartan (Entresto) is a separate drug that outperformed enalapril in PARADIGM-HF and is now preferred in HFrEF.

Prescribed when ACE inhibitors are not tolerated. Per ESC 2021, sacubitril/valsartan (Entresto) is preferred over valsartan monotherapy in HFrEF.

Hypertension

First line

First-line antihypertensive. Starting dose 80 mg once daily, maximum 320 mg. Prescribed as an ACE inhibitor alternative or when ACEi is not tolerated (cough). Frequently included in fixed-dose combinations with amlodipine and/or hydrochlorothiazide. Antihypertensive effect develops over 2-4 weeks.

Post-myocardial infarction heart failure

First line

Valsartan is an alternative to captopril in post-MI heart failure. The VALIANT trial (over 14,000 patients) showed that valsartan 160 mg twice daily was non-inferior to captopril for mortality and cardiovascular events. Prescribed for patients who do not tolerate ACE inhibitors.

Practical notes

Timing and administration

Take once daily at any time, with or without food. In heart failure, titration starts at 40 mg twice daily, increased to 160 mg twice daily. In hypertension, 80-320 mg once daily. Full antihypertensive effect in 2-4 weeks.

Monitoring

Check potassium and creatinine 1-2 weeks after initiation and each dose increase, same as other ARBs and ACE inhibitors. A creatinine rise up to 30% is acceptable. Larger rises warrant investigation for renal artery stenosis, hypovolemia, or concurrent NSAID use. Absence of cough is the key clinical differentiator from ACE inhibitors.

Safety

Contraindications

Pregnancy (all trimesters) – FDA category D
Severe hyperkalemia
Bilateral renal artery stenosis or stenosis of a single functioning kidney
Concurrent aliskiren in patients with diabetes or CKD
Severe hepatic impairment, biliary cirrhosis, cholestasis

Serious adverse effects

Angioedema (much less common than with ACEi, but possible)
Acute renal failure (in bilateral renal artery stenosis)
Life-threatening hyperkalemia (with potassium-sparing diuretics or aliskiren)

Common adverse effects

Dizziness
Hyperkalemia
Hypotension (more common with hypovolemia and in heart failure)
Creatinine elevation
Headache

PregnancyFDA 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.

Breastfeeding

No data on valsartan excretion in breast milk. Not recommended during breastfeeding. Alternative antihypertensives are chosen if therapy is needed.