What is the recommended dosage and treatment protocol for Valsartan (Angiotensin II receptor antagonist) in patients with hypertension and heart failure?

Valsartan Dosing for Hypertension and Heart Failure

Hypertension Dosing

For hypertension, start valsartan at 80-160 mg once daily and titrate up to a maximum of 320 mg once daily based on blood pressure response. 1

• The antihypertensive effect is substantially present within 2 weeks, with maximal reduction generally attained after 4 weeks 1
• If additional blood pressure reduction is needed beyond the starting dose, increase to a maximum of 320 mg daily or add a diuretic—adding a diuretic produces greater effect than dose increases beyond 80 mg 1
• Valsartan demonstrates dose-dependent efficacy over the 80-320 mg range, with the 160 mg dose providing sustained AT1-receptor blockade over 24 hours 2, 3

Pediatric Hypertension (Ages 1-16 Years)

• Start at 1 mg/kg once daily (up to 40 mg total), or consider 2 mg/kg in selected cases requiring greater blood pressure reduction 1
• Titrate according to blood pressure response up to a maximum of 4 mg/kg once daily (maximum 160 mg daily) 1
• Use oral suspension for children aged 1-5 years or those who cannot swallow tablets, noting that suspension provides 60% higher systemic exposure than tablets on a milligram-per-milligram basis 1

Heart Failure Dosing

For heart failure, start valsartan at 40 mg twice daily and uptitrate to the target dose of 160 mg twice daily, or to the highest dose tolerated by the patient. 1, 4

• The target dose of 160 mg twice daily (320 mg total daily dose) is critical—at least 50% of this target dose (160 mg daily total) represents the minimum effective dose for adequate treatment effect 4, 2
• Uptitrate from 40 mg twice daily → 80 mg twice daily → 160 mg twice daily, with dose adjustments made no more frequently than every 2 weeks 4, 2
• Consider reducing concomitant diuretic doses during uptitration 1
• The maximum daily dose studied in clinical trials is 320 mg in divided doses 1

Evidence Supporting Target Dosing

• Higher doses provide significantly greater benefits than lower doses—there is little evidence that subtarget doses yield survival benefits comparable to target doses 4
• In the Val-HeFT trial, valsartan 160 mg twice daily reduced the combined endpoint of mortality and morbidity by 13.2% compared with placebo when added to conventional heart failure therapy 4, 5
• Among patients not receiving an ACE inhibitor, valsartan reduced mortality risk by 33.1% and the combined endpoint by 44% 5

Dosing Frequency Consideration

• While twice-daily dosing is FDA-approved and studied in major trials, once-daily dosing at equivalent total daily doses (up to 320 mg) has demonstrated similar safety, tolerability, and 24-hour RAAS blockade in patients with NYHA class II-III heart failure 6
• However, stick with twice-daily dosing as this was the regimen proven in landmark trials 1, 5

Post-Myocardial Infarction Dosing

Initiate valsartan as early as 12 hours post-MI at 20 mg twice daily, uptitrate within 7 days to 40 mg twice daily, then to target maintenance dose of 160 mg twice daily as tolerated. 1

• If symptomatic hypotension or renal dysfunction occurs, consider dosage reduction 1
• Valsartan demonstrated noninferiority to captopril in post-MI patients in the VALIANT trial 4

Special Populations and Dose Adjustments

Renal Impairment

• For severe renal impairment (eGFR <30 mL/min/1.73 m²), start at 24/26 mg twice daily when using sacubitril/valsartan (this population was not studied in PARADIGM-HF) 7
• Monitor renal function closely during titration 4, 2

Hepatic Impairment

• For moderate hepatic impairment (Child-Pugh Class B), use lower starting doses 7

Elderly Patients (≥75 Years)

• Consider lower starting doses (24/26 mg twice daily for sacubitril/valsartan) 7

Critical Monitoring Parameters

Monitor blood pressure, renal function (serum creatinine), and electrolytes (particularly potassium) during dose titration. 4, 2

• Watch for symptomatic hypotension, doubling of serum creatinine, or serum potassium ≥5.5 mmol/L 7
• If these occur, consider temporary dose reduction but make efforts to restore target doses when possible to ensure optimal outcomes 4, 2

Common Pitfalls to Avoid

• Many physicians use doses that are too low for heart failure—this may not provide optimal benefits 2
• Do not delay uptitration unnecessarily; adjust doses every 2 weeks as tolerated to reach target doses 4, 2
• Temporary dose reductions may be necessary, but actively work to return patients to target doses rather than accepting subtarget dosing long-term 4, 2
• When switching between valsartan tablets and suspension, adjust the dose to account for the 60% higher systemic exposure with suspension 1

Transition from ACE Inhibitors

• For patients intolerant of ACE inhibitors, valsartan is a recommended alternative 4
• When transitioning to sacubitril/valsartan from an ACE inhibitor, observe a strict 36-hour washout period to avoid angioedema—this delay is not required when switching from an ARB 7