AVAPRO - APROVEL - GENERIC

OBJECTIVES AND DESIGN: An abnormal diastolic filling is common in hypertensive left ventricular (LV) hypertrophy, a condition that may lead to heart failure and death. The renin-angiotensin-aldosterone system has been implicated in the development of LV hypertrophy. This study examines the effects of 48 weeks of double-blind treatment with the AT1 receptor blocker irbesartan and the beta-blocker atenolol on diastolic function. METHODS: Diastolic function was evaluated in 115 hypertensive patients with LV hypertrophy by Doppler echocardiography mitral inflow velocities calculated from the peak of early (E) and peak of late (A) diastolic velocities (E/A ratio), the E-wave deceleration time, the isovolumic relaxation time, the pulmonary venous flow velocity, and by the atrioventricular valve plane displacement method. RESULTS: By similar reductions in blood pressure both groups progressively reduced the LV mass index, with a greater reduction in the irbesartan group (P = 0.024). Diastolic function was improved similarly by irbesartan and atenolol; for example, the E/A ratio by 12 and 14% (P = 0.022 and P < 0.001), and the pulmonary venous flow velocity by 10 and 7% (P = 0.036 and P = 0.001), respectively. The isovolumic relaxation time was improved by irbesartan (P = 0.040) only, and was related to changes in LV geometry (P < 0.001). For atenolol, improvement in diastolic function was associated only with the reduction in blood pressure (P = 0.048). An improvement in diastolic function appeared greater in concentric LV hypertrophy than in eccentric LV hypertrophy. CONCLUSIONS: Treatment based on atenolol or irbesartan improves diastolic function in patients with hypertensive LV hypertrophy to the same degree, but through different mechanisms.

BACKGROUND: The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome. METHODS AND RESULTS: We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups. CONCLUSIONS: Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.

GENERIC NAME: irbesartan
BRAND NAME: Avapro

DRUG CLASS AND MECHANISM: Irbesartan is among a class of drugs called angiotensin receptor blockers and is similar to losartan (Cozaar) and valsartan (Diovan). All three drugs block angiotensin II, a chemical that causes the arteries and veins to narrow, from attaching to the arteries and veins and causing them to narrow. As a result, the arteries and veins dilate (become larger), and blood pressure is reduced. When the blood pressure is reduced, the heart doesn't have to work as hard to pump blood. Irbesartan was approved by the FDA in 1998.

PREPARATIONS: Tablets: 75mg, 150mg, 300mg.

STORAGE: Tablets should be stored at room temperature, 15-30°C (59-86°F).

PRESCRIBED FOR: Irbesartan is used to treat high blood pressure. It may be used alone or in combination with other drugs. It has less of an effect in black patients, an effect that is similar to another class of drugs used to treat high blood pressure called ACE inhibitors--captopril (Capoten), enalapril (Vasotec), benazepril (Lotensin), and lisinopril (Zestril). Irbesartan is being studied in patients with congestive heart failure to determine if its blood pressure-lowering effects are beneficial to the heart.

DOSING: Irbesartan usually is taken once daily.

DRUG INTERACTIONS: No important drug interactions have been described with irbesartan. Since angiotensin receptor blockers such as irbesartan can increase the concentration of potassium in blood, other medications that also increase the concentration of potassium, such as hydrochlorothiazide (Dyazide) and spironolactone (Aldactone), as well as potassium supplements, should be used cautiously with irbesartan.

PREGNANCY: When used in the second or third trimester of pregnancy, drugs that work in a manner similar to irbesartan--specifically, ACE inhibitors such as enalapril (Vasotec)--can cause injury and even death to the fetus. Because of the possibility that irbesartan may have a similar effect on the fetus, it should not be used during pregnancy.

NURSING MOTHERS: Another angiotensin receptor blocker, losartan (Cozaar), is secreted in rat milk and is toxic to newborn rats. Since irbesartan is similar to losartan and may share a similar effect, irbesartan should be avoided in nursing mothers. The safety and efficacy of irbesartan in children has not been established.

SIDE EFFECTS: The most common side effects with irbesartan are diarrhea (occurring in 1 in 30 persons) and abdominal pain or heartburn (occurring in 1 in 50 persons). Glossary content Copyright © 1996-2002 MedicineNet, Inc. All rights reserved.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.