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Losartan (rINN) (IPA: ) is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure (hypertension). Losartan was the first angiotensin II receptor antagonist to be marketed. It is currently marketed by Merck & Co. under the trade name Cozaar.
Clinical use
As with all angiotensin II receptor antagonists, losartan is indicated for the treatment of hypertension. Losartan may also delay progression of diabetic nephropathy and is also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours).Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
Although angiotensin II receptor antagonists are not usually considered first-line, because of the proven effectivity and lower costs of thiazide diuretics and beta blockers, losartan may be used first-line in patients with increased cardiovascular risk. The LIFE study demonstrated that losartan was significantly superior to atenolol in the primary prevention of adverse cardiovascular events (myocardial infarction or stroke), with a significant reduction in cardiovascular morbidity and mortality for a comparable reduction in blood pressure.Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359(9311):995-1003. PMID 11937178
Combination with diuretic
Losartan is available in a combination formulation with a low dose thiazide diuretic, invariably hydrochlorothiazide, to achieve an additive antihypertensive effect. The losartan/hydrochlorothiazide combination preparation is marketed by Merck under the trade name Hyzaar.Research
Losartan has been found to downregulate the expression of transforming growth factor beta (TGF-β) types I and II in the kidney of diabetic rats, which may partially account for its nephroprotective effects.Guo ZX, Qiu MC. downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat Zhonghua Nei Ke Za Zhi 2003;42(6):403-8. PMID 12895325 Effects on TGF-β expression may also account for its potential efficacy in Marfan syndrome – losartan has been shown to prevent aortic aneurysm and certain pulmonary complications in a mouse model of the disease.Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 2006;312(5770):117-21. PMID 16601194
References
See also
"Losartan"