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

From the Guidelines

Losartan has been shown to have a significant effect on reducing cardiovascular morbidity and mortality, particularly in patients with hypertension and signs of left ventricular hypertrophy, with a lower risk for cardiovascular end points (RR, 0.76 [CI, 0.58 to 0.98]) and all-cause mortality (RR, 0.61 [CI, 0.45 to 0.84]) compared to beta-blockers 1. The primary mechanism of action of losartan is as an angiotensin II receptor antagonist, which blocks the action of angiotensin II, a hormone that causes blood vessels to narrow, thereby allowing blood vessels to relax and widen, which lowers blood pressure and improves blood flow. Key benefits of losartan include:

• Reduced risk of cardiovascular events, such as stroke and myocardial infarction
• Lower risk of all-cause mortality
• Renoprotective properties, which can help prevent or slow the progression of nephropathy in patients with diabetes
• Ability to be used in combination with other medications, such as diuretics and ACE inhibitors, to achieve targeted blood pressure goals. It is essential to note that losartan should be used with caution in certain patient populations, such as pregnant women, and regular monitoring of blood pressure and kidney function is recommended while taking this medication 1.

From the FDA Drug Label

Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT1 receptor Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25 to 40% inhibition persisting for 24 hours Treatment with losartan resulted in a 16% risk reduction in the primary endpoint of doubling of serum creatinine, end-stage renal disease (ESRD), or death. Losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints.

The effect of Losartan, an Angiotensin II receptor antagonist, is to:

• Block the vasoconstrictor and aldosterone-secreting effects of angiotensin II
• Inhibit the pressor effect of angiotensin II
• Reduce the risk of doubling of serum creatinine, end-stage renal disease (ESRD), and death by 16%
• Reduce the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% 2 2

From the Research

Effects of Losartan on Cardiovascular and Renal Health

• Losartan, an angiotensin II receptor antagonist, has been shown to be effective in reducing cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy 3.
• The LIFE study demonstrated that losartan is more effective than atenolol in reducing the composite primary endpoint of cardiovascular mortality, stroke, or myocardial infarction, mainly due to a significant reduction in the risk of stroke 3.
• Losartan has also been found to reduce the progression of nephropathy in type 2 diabetic patients with overt nephropathy, independently of changes in blood pressure 4.
• The use of losartan has been associated with a lower incidence of new-onset diabetes mellitus compared to atenolol 3.

Effects of Losartan on Left Ventricular Hypertrophy

• Losartan has been shown to facilitate the regression of left ventricular hypertrophy, which is a major risk factor for atrial fibrillation, diastolic heart failure, systolic heart failure, and sudden death in patients with hypertension 5.
• Combination therapy with losartan and a low-dose diuretic has been found to have greater potential for left ventricular hypertrophy regression compared to combination therapy with an angiotensin II receptor blocker and a calcium channel blocker 6.
• Angiotensin II receptor blockers, including losartan, have been found to provide cardioprotective effects similar to those of angiotensin-converting enzyme inhibitors, with beneficial effects on left ventricular hypertrophy regression and cardiac remodeling 7.

Renal Protection

• Losartan has been found to be effective in preventing the development of clinical proteinuria and delaying the progression of nephropathy in type 2 diabetic patients 4.
• The IRMA, IDNT, and RENAAL trials have demonstrated that angiotensin II receptor blockers, including losartan, are more effective than traditional antihypertensive therapies in reducing the progression of nephropathy in type 2 diabetic patients with overt nephropathy 4.