What is the effect of Losartan (Angiotensin II receptor antagonist) on hypertension?

From the Guidelines

Losartan is an effective medication for lowering blood pressure, with studies showing its ability to reduce cardiovascular morbidity and mortality, particularly in patients with hypertension and left ventricular hypertrophy 1. The medication works by blocking angiotensin II receptors, preventing the hormone from constricting blood vessels, and allowing them to relax and widen, thereby reducing resistance in the blood vessels and lowering blood pressure. According to the Losartan Intervention for Endpoint Reduction (LIFE) study, losartan was more effective in reducing cardiovascular events, particularly stroke, than the beta-blocker atenolol in 55-to-80-year-old hypertensive patients with evidence of left ventricular hypertrophy 1. Some key points to consider when prescribing losartan include:

• Starting dose: typically 50 mg once daily, potentially increased to 100 mg daily if needed
• Onset of action: within 1-2 weeks, with full effects seen after 3-6 weeks of regular use
• Common side effects: dizziness, fatigue, and occasional cough, though these are typically milder than with ACE inhibitors
• Monitoring: regular blood pressure and kidney function checks
• Administration: consistent timing each day, avoiding potassium supplements and salt substitutes containing potassium
• Missed dose: take as soon as remembered, but skip if almost time for the next dose The most recent and highest quality study, the 2007 guidelines for the management of arterial hypertension, supports the use of losartan as an antihypertensive treatment option, particularly in elderly patients 1. Overall, losartan is a valuable treatment option for patients with hypertension, particularly those with left ventricular hypertrophy or at risk for cardiovascular events, and its use should be considered in the context of individual patient needs and risk factors 1.

From the FDA Drug Label

The 10 mg and 25-mg doses produced some effect at peak (6 hours after dosing) but small and inconsistent trough (24 hour) responses Doses of 50 mg, 100 mg and 150 mg once daily gave statistically significant systolic/diastolic mean decreases in blood pressure, compared to placebo in the range of 5.5 to 10.5/3.5 to 7. 5 mmHg, with the 150-mg dose giving no greater effect than 50 mg to 100 mg. Losartan was effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients (usually a low-renin population)

Losartan's Effect on Blood Pressure:

• Losartan has been shown to reduce blood pressure in patients with hypertension.
• The drug's antihypertensive effects were demonstrated in 4 placebo-controlled trials, with doses of 50 mg, 100 mg, and 150 mg once daily resulting in statistically significant decreases in systolic and diastolic blood pressure.
• The effect of losartan on blood pressure was found to be dose-dependent, with higher doses resulting in greater reductions in blood pressure.
• Losartan was effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients 2.
• The mechanism of action of losartan involves blocking the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor 2.

From the Research

Losartan Effect on Blood Pressure

• Losartan is an orally active, nonpeptide, selective angiotensin subtype 1 (AT1) receptor antagonist that provides a more specific and complete blockade of the actions of angiotensin II than renin or ACE inhibitors 3.
• Short-term clinical trials have shown losartan to be as effective at lowering blood pressure in elderly patients with hypertension as recommended dosages of captopril, atenolol, enalapril, felodipine, and nifedipine, with a decrease in blood pressure of ≤ 26/20 mm Hg 3.
• The addition of hydrochlorothiazide to losartan therapy provides greater antihypertensive efficacy, equivalent to that seen with captopril plus hydrochlorothiazide 3.
• Losartan/hydrochlorothiazide fixed-dose combination therapy is an effective combination therapy, lowering blood pressure to a greater extent than losartan or HCTZ alone in patients with hypertension 4, 5, 6.
• This combination therapy is frequently recommended for the treatment of hypertension and lowers blood pressure in mild-to-moderate and even severe hypertensive patients to a level comparable with other classes of antihypertensive agents in combination with HCTZ 4, 6.
• The efficacy of losartan/hydrochlorothiazide in reducing blood pressure is similar to that of other combination therapies, such as candesartan/amlodipine 7.

Mechanism of Action

• Losartan blocks the actions of angiotensin II, a potent vasoconstrictor, which leads to a decrease in blood pressure 3.
• The combination of losartan with hydrochlorothiazide provides a synergistic effect, with losartan blocking the renin-angiotensin-aldosterone system and hydrochlorothiazide increasing sodium excretion, leading to a decrease in blood pressure 4, 5, 6.

Clinical Implications

• Losartan is a suitable option for first-line therapy in all patients with hypertension, particularly those who are not well managed with or who are intolerant of their current therapy 3.
• Losartan/hydrochlorothiazide fixed-dose combination therapy is a logical choice as antihypertensive therapy for patients in whom combination therapy is necessary to achieve additional blood pressure reduction 4, 6.
• This combination therapy is well tolerated and has a low risk of adverse effects, making it a suitable option for long-term treatment of hypertension 5, 7.