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Background and Purpose: Diet-induced hypercholesterolaemia exacerbates post-myocardial infarction (MI) ventricular remodelling and heart failure, but the mechanism of this phenomenon remains unknown. This study examined whether worsening of post-MI ventricular remodelling induced by dietary hypercholesterolaemia was related to upregulation of angiotensin II type 1 (AT1) receptor in the rat heart.Experimental Approach: MI was induced surgically in rats fed normal or high cholesterol diet. Both groups of rats were then assigned to control, atorvastatin, losartan or atorvastatin+losartan-treated subgroups and followed for 8 weeks. Left ventricular (LV) function was assessed with echocardiography. In isolated hearts, LV pressures were measured with a latex balloon and a tip catheter. AT1-receptor density was assessed in LV membranes with radioligand-binding assays.Key Results: High cholesterol diet exacerbated LV dilation and dysfunction in post-MI hearts. Atorvastatin or losartan prevented these hypercholesterolaemia-induced effects, whereas their combination was not more effective than each drug alone. AT1 receptors were upregulated 8 weeks after MI, this was further increased by hypercholesterolaemia and restored to baseline levels by atorvastatin.Conclusions and Implications: Hypercholesterolaemia exacerbated LV remodelling and dysfunction in post-MI rat hearts and upregulated cardiac AT1 receptors. All these effects were effectively prevented by atorvastatin. Thus, the pleiotropic statin effects may include interference with the renin-angiotensin system through downregulation of AT1 receptors. [ABSTRACT FROM AUTHOR]

Aims: This study assessed the clinical efficacy and safety of telmisartan, an angiotensin II receptor blocker with a long terminal elimination half-life and almost exclusively excreted in bile, in patients with varying severity of chronic kidney disease (CKD). Patients and methods: Adults with diastolic blood pressure (DBP) 90- 109 mmHg and stable CKD were enrolled: mild/moder- ate (creatinine clearance (CrCl) 30 - 74 ml/ minl/.73 m2), severe (CrCl <30 mIIminI/.73 m2) or requiring maintenance hemodialysis. A two- to four-week single-blind, placebo run-in period preceded once-daily telmisartan 40 mg administration for four weeks. Telmisartan 80 mg was given after four- or eight-week treatment if DBP ≥ 85 mmHg. After 12-week treatment, trough DBP!systolic blood pressure (SBP), DBP and SBP control rates, renal function and tolerability were recorded. Results: Mean changes in DBP/SBP were -10.5/-10.7 mmHg for mild/moderate CKD(n 27),-11.2/-14.9 mmHg for severe CKD (n = 27) and -15.0/-21.1 mmHg for hemodialysis patients (n = 28). DBP control rates (<90 mmHg)!SBP responses (< 140 mmHg or ≥ 10 mmHg reduction) occurred in 59.3%/66.7%, 63.0%/70.4% and 71.4%/92.9% of mild/moderate CKD, severe CKD and hemodialysis patients, respectively. mcidences of thug-related adverse events were low, and all were known adverse events of telmisartan and common to other angiotensin TI receptor blockers. At the end of treatment, a decrease in 24-h urine creatinine occurred in 5/53 (9.4%) patients. Two patients discontinued treatment prematurely due to the worsening of CKD and one due to aggravated proteinuria. Conclusion: Once-daily telmisartan provided effective and well-tolerated treatment of mild/moderate hypertension in CKD patients, with no worsening of renal function. [ABSTRACT FROM AUTHOR]

Background: Drugs that block the renin-angiotensin system represent one of the most significant therapeutic interventions available for the treatment of hypertension. The angiotensin II receptor antagonists (AIIRAs), also known as sartans, are one such class of drugs that block the effects of angiotensin II by antagonizing the angiotensin II type 1 receptor. Olmesartan is the newest member of this class.Objective: The present article reviews 3 head-to-head trials directly comparing the antihypertensive efficacy of olmesartan with that of 4 other AURAS, at recommended maintenance doses, already in clinical use for the treatment of hypertension.Results: In the first study, olmesartan 10 mg/d was compared with losartan 50 mg/d in 316 patients with mild to moderate hypertension (mean baseline diastolic blood pressure [DBP], 95–114 mm Hg). Dosage was doubled at week 4 and hydrochlorothiazide was added at week 12 if blood pressure response was inadequate. Olmesartan was significantly more effective than losartan with respect to the reduction in blood pressure at weeks 2, 4, and 12, and to the responder rate at weeks 2 and 4 (with the starting dose of the respective drug). In a second study, olmesartan 20 mg/d was shown to be significantly more effective than losartan 50 mg/d, valsartan 80 mg/d, and irbesartan 150 mg/d in 588 patients with mild to moderate hypertension (mean sitting baseline DBP, 100–115 mm Hg) (P ⩽ 0.05). At week 2, the reduction in blood pressure observed with olmesartan was significantly greater than that of the comparator treatments (P ⩽ 0.05). The superiority of olmesartan was maintained at week 8. The third study involved 643 evaluable patients with moderate to severe hypertension (mean DBP, 100–120 mm Hg; mean systolic blood pressure, >150 mm Hg). Olmesartan 20 mg/d was more effective than candesartan 8 mg/d in lowering 24-hour blood pressure at week 8 (P ⩽ 0.05). Most of this treatment effect was evident after only 1 or 2 weeks, with greater reductions in blood pressure compared with candesartan.Conclusions: These data indicate that, at the doses studied, olmesartan is more effective than other AIIRAs tested at their recommended doses, in terms of reduction of cuff or 24-hour ambulatory blood pressure, in patients with essential hypertension. These differences in blood pressure reduction between these agents may be clinically relevant and have important long-term implications. Additional studies will further define the role of olmesartan in the management of cardiovascular diseases, such as atherosclerosis. [Copyright &y& Elsevier]

Background: Olmesartan medoxomil is an angiotensin II receptor antagonist that selectively and competitively inhibits the angiotensin 11 type 1 receptor.Objective: This article reviews the results of some key studies that assessed the efficacy and tolerability of olmesartan in patients with hypertension.Methods: Olmesartan has been investigated in several clinical studies. This article reports on data from 1 such study with a prospective, randomized, double-blind, placebo-controlled, parallel-group, dose-finding design in patients with mild to moderate hypertension (baseline mean sitting diastolic blood pressure, 100–114 mm Hg). The results from a meta-analysis of 7 randomized, double-blind, placebo-controlled studies are also presented.Results: In the dose-finding study, 792 patients were randomized to olmesartan (2.5–80 mg) or placebo once daily, and changes were recorded in trough mean sitting diastolic and systolic blood pressures from baseline to the end of a 12-week treatment period. For the meta-analysis, 3055 patients were randomized to treatment; 2511 received olmesartan. In the dose-finding study as well as in the meta-analysis, olmesartan (2.5–80 mg once daily) produced a dose-dependent decrease in diastolic and systolic blood pressures, and at a dose of 10 to 80 mg showed significant superiority in reducing diastolic blood pressure over placebo (P < 0.05). The 20-mg dose was considered optimal, with a responder rate of 70%. Furthermore, in a 2-year study with 462 patients, olmesartan had a good safety profile and was well tolerated. The results of the clinical studies in >3000 patients receiving olmesartan showed that the frequency and profile of adverse events with olmesartan were generally similar to those with placebo; the frequency of adverse events was not dose related. Olmesartan, with or without hydrochlorothiazide, was well tolerated over 2 years of treatment. [Copyright &y& Elsevier]

Background: Poor compliance with treatment and early discontinuation negatively affect long-term blood pressure control. According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, poor compliance could contribute to the lack of adequate blood pressure control in ∼-70% of patients with hypertension, even after treatment with several anti-hypertensive drugs.Objective: This article discusses blood pressure control and patient compliance with antihypertensive drugs. It then outlines the clinical pharmacokinetics and interaction profile of the novel antihypertensive olmesartan medoxomil, an angiotensin II receptor antagonist (AIIRA), and relates the findings to the recommended dosing regimen and tolerability of the drug.Conclusions: Many factors influence patient compliance, including forgetfulness, adverse effects, irregular lifestyle, and complexity of drug regimen, such as multiple drugs and, in particular, frequent dosing. Drugs that are well tolerated and easy to manage in a once-daily regimen improve compliance. In a study of different classes of antihypertensive drugs, patients taking AURAS were more likely to continue their treatment than those taking any other class of antihypertensive. Therefore, the right drug choice may contribute to patient compliance. The newest member of the AIIRAs, olmesartan medoxomil, is a long-acting antihypertensive drug with a favorable safety and tolerability profile. It is not metabolized by and does not interfere with the cytochrome P-450 enzyme system. These properties meet modern requirements for the treatment of hypertension. [Copyright &y& Elsevier]