What is the recommended dosage and usage of Valsartan (Angiotensin II receptor antagonist) for adult patients with hypertension or heart failure, including those with diabetes or impaired renal function?

Valsartan Dosing and Usage

Hypertension

For adult hypertension, start valsartan at 80-160 mg once daily, with a maximum dose of 320 mg daily; the 160 mg dose provides optimal efficacy while maintaining a placebo-like tolerability profile. 1

Initial Dosing Strategy

• Start at 80 mg once daily for most patients, or 160 mg once daily if greater blood pressure reduction is needed 1
• Avoid starting at higher doses in volume-depleted patients 1
• The antihypertensive effect appears within 2 weeks, with maximal reduction at 4 weeks 1

Dose Titration

• If additional blood pressure reduction is needed beyond the starting dose, increase to a maximum of 320 mg once daily 1
• Adding a diuretic provides greater blood pressure reduction than dose increases beyond 80 mg 1
• Target blood pressure is <130/80 mmHg for patients with diabetes or chronic kidney disease, and <140/90 mmHg for others 2

Pediatric Hypertension (Ages 1-16 Years)

• Start at 1 mg/kg once daily (maximum 40 mg), or 2 mg/kg in selected cases requiring greater reduction 1
• Titrate up to maximum 4 mg/kg once daily (maximum 160 mg daily) based on response 1
• Use oral suspension for children 1-5 years old or those unable to swallow tablets—note that suspension provides 60% higher systemic exposure than tablets, requiring dose adjustment when switching 1
• Do not use in children under 1 year of age 1

Heart Failure

For heart failure with reduced ejection fraction, target valsartan 160 mg twice daily (320 mg total daily dose), as higher doses provide significantly greater benefits than lower doses. 3

Initiation and Titration

• Start at 40 mg twice daily 1
• Uptitrate every 2 weeks to 80 mg twice daily, then 160 mg twice daily, or to the highest tolerated dose 1, 3
• The maximum studied dose is 320 mg daily in divided doses 1
• Consider reducing concomitant diuretic doses during uptitration 1

Critical Dosing Considerations

• At least 50% of target dose (160 mg daily total) is recommended as the minimum effective dose 3
• Many physicians underdose valsartan in heart failure—less than 25% of patients are titrated to target doses in clinical practice, which compromises outcomes 3
• The 160 mg twice daily dose achieves sustained AT1-receptor blockade over 24 hours 3
• Temporary dose reductions may be necessary for hypotension or renal dysfunction, but efforts should be made to return to target doses 3

Evidence Base

• The Val-HeFT trial demonstrated a 13.2% reduction in cardiovascular mortality and morbidity with valsartan up to 320 mg/day 3, 4
• In patients not receiving an ACE inhibitor, valsartan reduced mortality by 33.1% and the combined endpoint by 44% 4
• Important caveat: In patients already taking both an ACE inhibitor and beta-blocker, adding valsartan increased mortality 4

When to Use Valsartan in Heart Failure

• Valsartan is indicated for symptomatic heart failure (NYHA class II-IV) in patients intolerant of ACE inhibitors 2, 4
• ACE inhibitors remain the first-line agent for renin-angiotensin-aldosterone system inhibition 2
• Do not combine valsartan with ACE inhibitors—the VALIANT study showed equivalent outcomes but more adverse effects with combination therapy 2
• If combination ACE inhibitor and ARB therapy is deemed necessary, candesartan is preferred over valsartan based on the CHARM-Added trial 2

Modern Alternative: ARNI Consideration

• Sacubitril/valsartan (ARNI) is now preferred over valsartan alone in eligible HFrEF patients, reducing cardiovascular death or HF hospitalization by 20% compared to enalapril 5
• ARNI can be initiated de novo in hospitalized patients before discharge 5
• When switching from valsartan to ARNI: use 49/51 mg twice daily if previously on valsartan ≥160 mg daily equivalent 5

Post-Myocardial Infarction

For post-MI patients with heart failure, LV dysfunction (EF ≤40%), or both, initiate valsartan at 20 mg twice daily as early as 12 hours post-MI, titrating to target 160 mg twice daily. 1

Dosing Protocol

• Start at 20 mg twice daily as early as 12 hours after MI 1
• Uptitrate within 7 days to 40 mg twice daily 1
• Continue titration to target maintenance dose of 160 mg twice daily as tolerated 1
• If symptomatic hypotension or renal dysfunction occurs, reduce dose 1

Evidence and Indications

• The VALIANT trial demonstrated valsartan 160 mg twice daily was noninferior to captopril for mortality outcomes 2, 3
• Valsartan is indicated for post-STEMI patients with symptomatic heart failure who are intolerant of ACE inhibitors 2
• Can be combined with standard post-MI treatment including thrombolytics, aspirin, beta-blockers, and statins 1

Special Populations

Diabetes and Chronic Kidney Disease

• Target blood pressure <130/80 mmHg in patients with diabetes or chronic kidney disease 2
• Valsartan reduces urinary albumin and protein excretion in type 2 diabetes and nondiabetic CKD 6
• Most patients require 2 or more drugs to reach blood pressure goals 2

Renal Impairment

• Exercise caution when creatinine >221 μmol/L (>2.5 mg/dL) or eGFR <30 mL/min/1.73 m² 3
• No data available for pediatric patients on dialysis or with GFR <30 mL/min/1.73 m² 1
• Monitor renal function 1-2 weeks after initiation and after each dose increase 3

Monitoring Requirements

Essential Monitoring Parameters

• Check blood pressure, renal function, and potassium 1-2 weeks after initiation or dose increases, then every 3-6 months 3
• Monitor for symptomatic hypotension, especially when systolic BP <90 mmHg 3
• Significant hyperkalemia (K+ >5.0 mmol/L) requires specialist advice and close monitoring 3

Drug Interactions and Contraindications

• Avoid NSAIDs unless essential—they attenuate diuretic effects and cause renal impairment 3
• Do not combine with ACE inhibitors due to increased risk of hyperkalemia and renal dysfunction 3
• Avoid potassium supplements, potassium-sparing diuretics, and "low-salt" substitutes with high potassium content 3
• Reconsider need for nitrates, calcium-channel blockers, and other vasodilators if symptomatic hypotension develops 3

Tolerability Profile

Valsartan has an excellent safety profile comparable to placebo, with significantly lower incidence of cough and rare angioedema compared to ACE inhibitors. 7, 6, 8

• Adverse events are similar to placebo in most studies 7, 6
• No first-dose hypotension or rebound hypertension on abrupt withdrawal 8
• No adverse metabolic effects 8
• Most common adverse events leading to discontinuation: dizziness, renal impairment, and hypotension 4