What is the optimal dosing strategy for patients on a low Angiotensin II Receptor Blocker (ARB) dosage, such as losartan (Losartan), for blood pressure control?

From the Guidelines

For patients on a low dose of an ARB like losartan for blood pressure control, the optimal dosing strategy typically involves gradual dose titration based on blood pressure response and tolerability, starting with losartan 25-50 mg once daily and increasing to the target dose of 100 mg daily if blood pressure remains above goal after 2-4 weeks, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. The goal is to achieve a blood pressure of less than 130/80 mmHg, and dose adjustments should be made gradually to minimize side effects such as dizziness or hypotension. For elderly patients or those with renal impairment, starting at 25 mg daily is recommended with more cautious titration, as indicated in the 2007 KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease 1. Blood pressure should be monitored regularly, ideally at home with periodic clinical confirmation. If maximum losartan dose doesn't achieve target blood pressure, adding a complementary agent like a thiazide diuretic (e.g., hydrochlorothiazide 12.5-25 mg daily) is often more effective than further increasing the ARB dose, as suggested by the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1. This stepped approach maximizes efficacy while minimizing side effects because ARBs work by blocking angiotensin II receptors, reducing vasoconstriction and sodium retention, with most of the blood pressure-lowering effect achieved at moderate doses while higher doses primarily extend the duration of action rather than significantly enhancing the magnitude of effect. Key considerations include:

• Starting dose: 25-50 mg once daily
• Target dose: 100 mg daily
• Dose adjustment: Gradual, based on blood pressure response and tolerability
• Monitoring: Regular blood pressure checks, ideally at home with periodic clinical confirmation
• Additional therapy: Consider adding a thiazide diuretic if maximum losartan dose is not effective.

From the FDA Drug Label

The usual starting dose of losartan is 50 mg once daily. The dosage can be increased to a maximum dose of 100 mg once daily as needed to control blood pressure [see CLINICAL STUDIES (14.1)]. A starting dose of 25 mg is recommended for patients with possible intravascular depletion (e.g., on diuretic therapy).

The optimal dosing strategy for patients on a low Angiotensin II Receptor Blocker (ARB) dosage, such as losartan, for blood pressure control is to start with a dose of 50 mg once daily and increase to a maximum dose of 100 mg once daily as needed. A lower starting dose of 25 mg is recommended for patients with possible intravascular depletion.

• The dosage should be adjusted according to blood pressure response.
• Doses above 100 mg daily have not been shown to provide additional benefit in reducing blood pressure. 2

From the Research

Optimal Dosing Strategy for Low Angiotensin II Receptor Blocker (ARB) Dosage

The optimal dosing strategy for patients on a low Angiotensin II Receptor Blocker (ARB) dosage, such as losartan, for blood pressure control can be determined by considering the following factors:

• The recommended dosage of losartan is 50 mg/day, which can be administered without regard to food 3
• The maximum recommended daily dose of losartan is 100mg, which can be given as a once-daily dose or by splitting the same total daily dose into two doses 3
• Losartan reduces blood pressure comparably to other angiotensin-receptor antagonists 3
• The concomitant administration of losartan potassium, 50 mg, with 12.5 mg of hydrochlorothiazide once daily produced an additive reduction in trough sitting systolic and diastolic blood pressure and was well tolerated 4

Key Considerations

• The pharmacokinetics of losartan and its active metabolite E 3174 are linear, dose-proportional and do not substantially change with repetitive administration 3
• There are no clinically significant effects of age, sex or race on the pharmacokinetics of losartan, and no dosage adjustment is necessary in patients with mild hepatic impairment or various degrees of renal insufficiency 3
• Losartan does not have a drug-drug interaction with hydrochlorothiazide, warfarin or digoxin 3
• Losartan potassium lowers blood pressure measured by ambulatory blood pressure monitoring, with all doses significantly decreasing mean systolic 24-h ambulatory blood pressure and mean diastolic 24-h ambulatory blood pressure compared with placebo 5

Comparison with Other Antihypertensive Agents

• Amlodipine and losartan, with or without hydrochlorothiazide (HCTZ), were compared for the treatment of mild to moderate hypertension, with amlodipine showing greater reductions in most blood pressure measurements 6
• The response rate was significantly greater after treatment with amlodipine than with losartan in African Americans and the other mostly Hispanic patients 6

Dosage Adjustment

• Patients who fail to meet the sitting diastolic blood pressure reduction goal of <or=90 mm Hg after 6 weeks may require a dose increase or the addition of hydrochlorothiazide 6
• The dosage adjustment should be based on the individual patient's response to treatment and their blood pressure goals 6