SEARCH · Search PubMed

Results for “Irbesartan”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1997

24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators' Group.

OBJECTIVES: To compare 24 h ambulatory blood pressure and trough office blood pressure lowerings after 8 weeks of therapy with 75 mg irbesartan once a day, 150 mg irbesartan once a day , and 75 mg irbesartan twice a day versus placebo; and to assess safety and tolerability of irbesartan therapy. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Sixteen centers in Italy. PATIENTS: Caucasian patients (n = 215) aged > or = 18 years with seated diastolic blood pressure 95-110 mmHg and ambulatory diastolic blood pressure (ADBP) > or = 85 mmHg. PRIMARY OUTCOME: Mean 24 h ADBP after 8 weeks of irbesartan therapy. RESULTS: Mean changes (value before treatment minus value after treatment) in ADBP for placebo, 75 mg irbesartan once a day, 150 mg irbesartan once a day, and 75 mg irbesartan twice a day were -0.2, -5.4, -7.2, and -7.2 mmHg, respectively; respective changes in ambulatory systolic blood pressure were +1.6, -8.3, -10.5, and -9.7 mmHg. All irbesartan regimens reduced trough office seated diastolic blood pressure and seated systolic blood pressure after 2 and 8 weeks of treatment (all P < 0.01, versus placebo except for seated systolic blood pressure in patients in the 75 mg irbesartan once a day group). Trough: peak ratios were > or = 55% with 150 mg irbesartan once a day. Percentages of patients whose blood pressures were normalized with 150 mg irbesartan once a day (45%) and 75 mg irbesartan twice a day (47%) were greater than those with placebo (14%, P < 0.01) and with 75 mg irbesartan once a day (19%, NS, versus placebo). Adverse events with irbesartan were similar to those with placebo. CONCLUSIONS: All irbesartan regimens significantly reduced mean 24 h ADBP and ambulatory systolic blood pressure, and were well tolerated. Administration of 150 mg irbesartan once a day provided significant reduction of blood pressure for 24 h, equivalent to that obtained with the same daily dose divided into two separate administrations.

Aged↗

PubMed2004

Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease.

OBJECTIVE: The aim of this study was to determine the most cost-effective time point for initiation of irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease. RESEARCH DESIGN AND METHODS: This study was a Markov model-simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease, and death in hypertensive patients with type 2 diabetes. Two irbesartan strategies were created: early irbesartan 300 mg daily (initiated with microalbuminuria) and late irbesartan (initiated with overt nephropathy). These strategies were compared with control, which consisted of antihypertensive therapy with standard medications (excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) with comparable blood pressure control, initiated at microalbuminuria. Transition probabilities were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial, and other published sources. Costs and life expectancy, discounted at 3% yearly, were projected over 25 years for 1,000 simulated patients using a third-party payer perspective in a U.S. setting. RESULTS: Compared with control, early and late irbesartan treatment in 1,000 patients were projected to save (mean +/- SD) 11.9 +/- 3.3 million dollars and 3.3 +/- 2.7 million dollars, respectively. Early use of irbesartan added 1,550 +/- 270 undiscounted life-years (discounted 960 +/- 180), whereas late irbesartan added 71 +/- 40 life-years (discounted 48 +/- 27) in 1,000 patients. Early irbesartan treatment was superior under a wide-range of plausible assumptions. CONCLUSIONS: Early irbesartan treatment was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of irbesartan in overt nephropathy is also superior to standard care, but irbesartan should be started earlier and continued long term.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study.

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.

Adult↗

PubMed2006

Tissue velocity echocardiography shows early improvement in diastolic function with irbesartan and atenolol therapy in patients with hypertensive left ventricular hypertrophy. Results form the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA).

BACKGROUND: Abnormal diastolic function is common in hypertensive left ventricular hypertrophy (LVH). Early identification and treatment may prevent future cardiovascular events. METHODS: We examined 58 hypertensive patients with LVH, 38 with hypertension but no LVH, and 38 normotensive subjects. The effects of the AT1 receptor blocker irbesartan and the beta1 blocker atenolol on diastolic function during 48 weeks of treatment were evaluated in the LVH group by tissue velocity echocardiography (TVE). We measured basal septal and lateral wall velocities of early (Em) and late (Am) diastolic myocardial wall motion, Em velocity deceleration time (E-decm), and isovolumic relaxation time (IVRTm). For comparison, diastolic function was assessed by conventional mitral pulse wave Doppler echocardiography. RESULTS: Diastolic function was impaired in both hypertensive groups. Irbesartan and atenolol (week 48, septal wall) improved IVRTm (-44%, P<.001, and -19%, P<.001; P<or=.001 between groups), E-decm (+56%, P<.001, and +53%, P<.001), and Em/Am (+11%, P=.396, and +20%, P=.010). Only irbesartan improved E/Em (-4%, P=.052 v +2%, P=.041). For irbesartan, relative changes in IVRTm and in septum thickness were related (P=.017), whereas relative changes in the Em/Am ratio and in heart rate were related for atenolol (P=.027). Alterations in diastolic dysfunction were greater and detected earlier with TVE than with conventional echocardiography. CONCLUSIONS: The TVE is more sensitive than conventional echocardiography in detecting alterations in diastolic function. Both irbesartan and atenolol improve diastolic function, but through different mechanisms. The improvement in IVRTm was greater with irbesartan, and only irbesartan improved E/Em. This may have implications on the treatment of high risk hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed2005

Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension.

BACKGROUND: Individual variations in the pharmacokinetics and pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension. OBJECTIVE: This study examined the relationship between ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension. METHODS: Patients with essential hypertension who had taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP) <90 mm Hg (DBP analysis), a systolic BP (SBP) <140 mm Hg (SBP analysis), and a DBP <90 mm Hg and SBP <140 mm Hg (DBP and SBP analysis). RESULTS: The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: -2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: -12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBP > or =100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: -5.7 [1.4] mm Hg; P < 0.001) and SBP compared with those with the Val/Val genotype and a baseline DBP > or =100 mm Hg (adjusted regression coefficient: -9.8 [2.9] mm Hg; P < 0.001). CONCLUSION: The findings of this study suggest that in these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.

Adult↗

PubMedDate not supplied

CYP2C9 Ile359Leu polymorphism, plasma irbesartan concentration and acute blood pressure reductions in response to irbesartan treatment in Chinese hypertensive patients.

Our previous study demonstrated that the CYP2C9*3 gene variant was significantly associated with elevated plasma irbesartan concentration and blood pressure decline, assessed by a 4-week follow-up and revisit following daily administration of irbesartan. We conducted a further analysis to examine the acute effects of the CYP2C9 polymorphism on plasma concentration and blood pressure through remeasurement 6 h after administration of irbesartan. We used an extreme-sampling approach by selecting individuals from the top and bottom deciles of blood pressure response residuals to irbesartan from the previous study population in Anhui, Taihu, and Dongzhi Counties, in China. A total of 196 subjects were available for the analysis. Pre- and posttreatment systolic and diastolic blood pressures (SBP and DBP), and venous blood samples (0.5, 2, and 6 h following the first treatment) were collected from each individual. Plasma irbesartan concentrations were determined by a standard HPLC/fluorescence method. The observed frequencies were 97.7% for CYP2C9*1 (Ile359) and 2.3% for CYP2C9*3 (Leu359). Subjects with the CYP2C9*1/CYP2C9*3 genotype had significantly higher plasma irbesartan concentrations when compared with those with the CYP2C9*1/CYP2C9*1 genotype (beta +/- SE = 81 +/- 36) and greater DBP response (beta +/- SE = 5.6 +/- 2.5 mmHg) at the 6-h time point after adjusting for important confounders. Our finding suggests that the CYP2C9*3 gene variant significantly alters the plasma concentration and acute DBP response at the 6-h point following irbesartan treatment in Chinese hypertensive patients.

Administration, Oral↗

PubMed2002

The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial.

BACKGROUND: The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT(1)) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1(wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated. OBJECTIVE: To determine whether the CYP2C9genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan. DESIGN AND METHODS: One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol ( n= 53). Blood pressure was measured before and after 12 weeks of treatment. genotyping was performed using solid-phase minisequencing. RESULTS: The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% ( P= 0.036). A similar trend was seen for systolic blood pressure. In contrast, no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9. CONCLUSIONS: The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension.

Adult↗

PubMed2003

Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).

We examined long-term influence of the angiotensin II type 1-receptor blocker irbesartan and the beta1-adrenergic receptor blocker atenolol on some neurohormonal systems implicated in the pathophysiology of cardiac hypertrophy. Thus, 115 hypertensive patients with left ventricular hypertrophy were randomized to receive double-blind irbesartan or atenolol, with additional therapy if needed. Neurohormone measurements and echocardiography were performed at weeks 0, 12, 24, and 48. Left ventricular mass was reduced more by irbesartan than by atenolol (-26 g/m2 versus -14 g/m2, P = 0.024), despite similar reductions in blood pressure. Plasma renin activity and angiotensin II increased (P < 0.001) by irbesartan (0.9 +/- 0.7 to 3.4 +/- 4.2 ng/mL x h, and 3.0 +/- 1.6 to 13.0 +/- 17.7 pmol/L), but decreased (P < 0.01) by atenolol (1.0 +/- 0.6 to 0.7 +/- 0.6 ng/mL x h, and 3.4 +/- 1.6 to 3.2 +/- 2.2 pmol/L). Serum aldosterone decreased (P < 0.05) by both irbesartan (346 +/- 140 to 325 +/- 87 pmol/L) and atenolol (315 +/- 115 to 283 +/- 77 pmol/L). Changes in left ventricular mass by irbesartan related inversely to changes in plasma renin activity, angiotensin II, and aldosterone (all P < 0.05). Plasma levels and 24-hour urinary excretions of catecholamines, plasma leptin, proinsulin, insulin and insulin sensitivity remained largely unchanged in both groups. Thus, the renin-angiotensin aldosterone system appears to be an important non-hemodynamic factor in the regulation of left ventricular mass.

Adult↗

PubMed2003

Comparative effects of Irbesartan on ambulatory and office blood pressure: a substudy of ambulatory blood pressure from the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study.

OBJECTIVE: Irbesartan was renoprotective independently of its blood pressure-lowering effect in the Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria (IRMA2) study. However, blood pressure was evaluated by trough office blood pressure (OBP), which may underestimate reductions in 24-h ambulatory blood pressure (ABP). In the present study, we evaluated 24-h blood pressure patterns in a subpopulation of the IRMA2 trial. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (n = 43) with persistent microalbuminuria (as determined by repeated overnight measurements of urinary albumin excretion [UAE]) and hypertension who were included in the IRMA2 study at the Steno Diabetes Center were subjected to 24-h ABP (Takeda, TM2420) measurements before and 2 years after randomization to placebo (n = 15), irbesartan 150 mg daily (Irb150; n = 13), or irbesartan 300 mg daily (Irb300; n = 15). RESULTS: At baseline, the placebo, Irb150, and Irb300 groups were comparable: OBP: 157 +/- 15/89 +/- 7, 156 +/-15/91 +/- 11, and 159 +/- 16/90 +/- 9 mmHg (NS); 24-h ABP: 148 +/- 13/83 +/- 11, 148 +/- 16/82 +/- 7 and 147 +/- 16/81 +/- 10 mmHg (NS); and UAE (geometric mean with 95% CI): 43 (32-57), 46 (30-70), and 59 (42-85) micro g/min (NS), respectively. We found that 2 years after randomization, OBP was significantly reduced in all three groups (by 11/7, 13/8, and 13/8 mmHg in the placebo, Irb150, and Irb300 groups, respectively), but that there were no significant differences among groups. Reductions in 24-h ABP were similar in the three groups (11/10, 5/7, and 7/8 mmHg, respectively; NS), as were reductions in day ABP (11/9, 7/7, and 8/9 mmHg, respectively; NS) and night ABP (4/11, 7/7, and 3/3 mmHg, respectively; NS). The reduction in UAE at the end of the study was 0% (-86 to 42), 38% (-14 to 66), and 73% (59 to 82), respectively (overall, P < 0.01). CONCLUSION: Irbesartan is renoprotective independently of its beneficial effect in lowering 24-h blood pressure in patients with type 2 diabetes and persistent microalbuminuria.

Adult↗

PubMed2002

Comparison of actions of irbesartan versus atenolol on cardiac repolarization in hypertensive left ventricular hypertrophy: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA).

Left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. The effects of antihypertensive therapy on QT dispersion, which reflects cardiac repolarization heterogeneity, in relation to changes in LV mass has not been well studied. Repeat echocardiography and QT measurements (standard 12-lead electrocardiograms) were performed in hypertensive patients with LV hypertrophy, who were randomized double-blind to receive the angiotensin II type 1-receptor blocker irbesartan (n = 44) or the beta(1)-receptor blocker atenolol (n = 48) for 48 weeks, and in 37 matched hypertensive control subjects without LV hypertrophy. LV mass index was related to QT dispersion (r = 0.34, p <0.001). The reduction in LV mass was greater using irbesartan than using atenolol (-27 +/- 28 vs -15 +/- 21 g/m(2) at 48 weeks, p = 0.021), with similar reductions in blood pressure. Irbesartan decreased QT dispersion (from 56 +/- 24 ms to 45 +/- 20 ms at 48 weeks; p <0.001) and QTc dispersion (from 57 +/- 24 to 44 +/- 19 ms at 48 weeks; p <0.001). In contrast, atenolol had minor effects. The decreases in QT and QTc dispersions were greater using irbesartan than using atenolol (p = 0.001 and p = 0.011, respectively); the same results were found when changes in LV mass, blood pressure, and heart rate were also included in multivariate analyses. Thus, heterogeneity of ventricular repolarization is related to the degree of LV hypertrophy. Irbesartan, but not atenolol, reduces QT and QTc dispersions independent of changes in LV mass, blood pressure, or heart rate, and thus seems to induce structural and electrical remodeling in a direction that could decrease the risk of fatal events in hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed2003

An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings.

BACKGROUND: In the Irbesartan in Diabetic Nephropathy Trial (IDNT), treatment with irbesartan demonstrated 23 and 20% reductions in the combined endpoint of doubling of serum creatinine (DSC), end-stage renal disease (ESRD) or death in patients with hypertension, type 2 diabetes and overt nephropathy compared with amlodipine and control, respectively. A simulation model was developed to project long-term cost consequences of the IDNT in Belgium and France. METHODS: A Markov model simulated progression from nephropathy to DSC, ESRD and death in patients with hypertension, type 2 diabetes and overt nephropathy. Treatment-specific probabilities were derived from IDNT. Country-specific ESRD-related data were retrieved from published sources. Delay in onset of ESRD, life expectancy and mean lifetime costs were calculated for patients with a baseline age of 59 years. Future costs were discounted at 3% per annum (p.a.), and clinical benefits were discounted at 0 and 3% p.a. Extensive sensitivity analyses were performed. RESULTS: Onset of ESRD was delayed with irbesartan by 1.41 and 1.35 years vs amlodipine and control, respectively. When a 10-year time horizon was considered, delay in ESRD onset led to anticipated improvements in life expectancy of 0.13 years vs amlodipine and 0.26 years vs control. Irbesartan was associated with cost savings of 14 949 and 9205/patient in Belgium, and 20 128 and 13 337 in France, vs amlodipine and control, respectively. The results were robust under a wide range of plausible assumptions. CONCLUSIONS: Treating patients with hypertension, type 2 diabetes and overt nephropathy using irbesartan was both cost- and life-saving compared with amlodipine and control.

Adult↗

PubMed2004

Effect of irbesartan versus atenolol on left ventricular mass and voltage: results of the CardioVascular Irbesartan Project.

Regression of hypertensive left ventricular hypertrophy (LVH) is associated with improved prognosis. The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension. Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information, both methods were applied in this trial. In the randomized, double-blind, multicenter trial CardioVascular Irbesartan Project, 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months. Voltage criteria used for LVH were Sokolow index, Cornell index, Cornell voltage x QRS duration product and Lewis index. In parallel, left ventricular mass (LVM) was determined by 2-dimensional guided M-mode echocardiography. After 6 and 18 months, reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan. However, a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall. In contrast, reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits. In conclusion, treatment of hypertension with irbesartan resulted in a significant reduction in the voltage criteria for LVH, although an effect on LVM was only seen in subjects with high baseline LVM. In contrast, atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH. Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM, we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment.

Adrenergic beta-Antagonists↗

PubMed2004

Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial.

BACKGROUND: It is important to know the reliability of early changes in proteinuria in predicting late renal outcomes. The IDNT was a trial in which treatment assignment, baseline and follow-up blood pressure determinations, and albumin/creatinine ratios (ACR), and renal outcomes were recorded. METHODS: Risk of renal outcomes in the IDNT was assessed by proportional hazards modeling as a function of treatment assignment, and achieved systolic blood pressure (SBP) both without, and then with, inclusion of values for baseline proteinuria and early changes in proteinuria. RESULTS: In models without ACR variables, both treatment with irbesartan and achieved SBP during follow-up were significantly predictive of the risk of renal outcomes. Addition of ACR variables to the models reduced the apparent impact of assignment to irbesartan by 52% to 81%, and irbesartan was no longer a significant predictor of renal outcomes. Conversely, addition of ACR variables to the models attenuated the effect of achieved follow-up SBP by only 32% to 46%, and follow-up BP remained a highly significant predictor of renal outcomes. CONCLUSION: The ability of early changes in proteinuria to predict the impact of treatment on renal outcomes is a function of the specific treatment. One must use caution in using early changes in proteinuria as a surrogate for longer-term renal outcomes.

Antihypertensive Agents↗

PubMedDate not supplied

A study of the efficacy and safety of irbesartan in combination with conventional therapy, including ACE inhibitors, in heart failure. Irbesartan Heart Failure Group.

Because heart failure therapy with angiotensin-converting enzyme (ACE) inhibitors may not be optimal, owing to persistent levels of angiotensin II occurring through incomplete blockade and alternate pathways, the benefit of adding irbesartan, an angiotensin receptor antagonist, to conventional therapy, including ACE inhibitors, was examined. In this multicentre, randomised, double-blind, placebo-controlled study, 109 patients with heart failure (New York Heart Association functional class II and III) and left ventricular ejection fraction (LVEF) < or = 40% received stable doses of ACE inhibitors and diuretics before and throughout the study. Irbesartan was titrated as tolerated to 150 mg once daily in all patients. Exercise tolerance time (ETT), LVEF and clinical status were assessed at baseline and after 12 weeks. Compared with placebo, irbesartan in combination with conventional therapy, including ACE inhibitors, produced favourable trends in ETT and LVEF and was well tolerated in patients with mild to moderate heart failure.

Adult↗

PubMed1997

Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators.

In this double-blind, randomized study, an antihypertensive regimen based on irbesartan, an angiotensin II receptor antagonist, reduced systolic and diastolic blood pressure by 40/30 mm Hg at week 12 in patients with severe hypertension; this reduction was at least equivalent to that of a regimen using enalapril up to 40 mg. The irbesartan-based regimen had a better tolerability profile with fewer adverse events (55% vs 64%) and significantly less cough (2.5% vs 13.1%, p = 0.007).

Angiotensin II↗

PubMed1998

Comparison of irbesartan vs felodipine in the regression after 1 year of left ventricular hypertrophy in hypertensive patients (the SILVER trial). Study of Irbesartan in Left VEntricular hypertrophy Regression.

The SILVER (Study of Irbesartan in Left VEntricular hypertrophy Regression) trial is designed to test the hypothesis that the newly developed angiontensin-II receptor antagonist, irbesartan, will produce a greater reduction in left ventricular (LV) mass than felodipine ER, in a population of hypertensive patients defined by seated diastolic blood pressure (SeDBP) in the range 95-115 mmHg or seated systolic blood pressure (SeSBP) in the range 160-200 mm Hg. A population of 360 men and women of non-childbearing potential, >18 years of age, with hypertension, newly diagnosed or after a 3-week washout from previous anti-hypertensive or vasodilator therapies, will be randomised at approximately 80-90 European sites. Add-on therapy with hydrochlorothiazide and atenolol will be allowed for blood pressure control. Patients will be studied by two-dimensional and M-mode echocardiography at baseline (central validation of LV hypertrophy), on randomisation day, and after 6 and 12 months randomised therapy. Blinded analysis of echocardiograms will be performed at a central laboratory, which will provide measurements of the LV mass index (LVMI), determined by M-mode readings according to Devereux formula and using the Penn convention. The primary end-point of the study will be the change in LVMI from baseline to 12 months. The study power is 90% to detect differences between groups from baseline of approximately 8 g/m2.

Adolescent↗

PubMed1999

The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group.

In a multicenter, double-blind, randomized trial, 178 patients with ambulatory diastolic blood pressure (BP) > or =85 mm Hg and seated diastolic BP (SeDBP) 95-110 mm Hg received either once-daily irbesartan 75 mg/hydrochlorothiazide (HCTZ) 12.5 mg, irbesartan 150 mg/HCTZ 12.5 mg, or placebo for 8 weeks to assess reductions in 24-hour ambulatory BP and office BP. Safety and tolerability of all treatment regimens were also evaluated. BP results and therapeutic response (trough SeDBP normalized to <90 mm Hg) were expressed as change from baseline to Week 8. Mean reductions in 24-hour ambulatory BP and office seated BP for irbesartan/HCTZ combinations were significantly greater compared with placebo (all, p<0.01). More patients were normalized with irbesartan/HCTZ (65%-69%) than placebo (24%, p<0.01). The frequency of adverse events was similar in all groups. Irbesartan/HCTZ given once-daily appears to be a well-tolerated, safe, and effective antihypertensive treatment.

Adult↗

PubMed2004

Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy.

Irbesartan (Avapro, Aprovel) is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily administration of irbesartan provided 24-hour control of blood pressure (BP). In patients with mild-to-moderate hypertension irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than valsartan in terms of absolute reduction in BP and response rates. Irbesartan produced a greater reduction in diastolic BP at trough than once-daily losartan, but had a smaller effect than olmesartan; the reduction in systolic BP achieved with irbesartan was similar or greater than that with losartan and similar to that seen with olmesartan. The combination of irbesartan with hydrochlorothiazide produced additive effects on BP reduction. Irbesartan also induced regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy. In two large studies (IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients [IRMA 2] and the Irbesartan Diabetic Nephropathy Trial [IDNT]) irbesartan exerted a renoprotective effect in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. The renoprotective effect was at least partly independent of the BP-lowering effect. In the IRMA 2 trial, the proportion of patients progressing to overt nephropathy was significantly lower for recipients of irbesartan 300mg once daily than placebo. In patients with overt nephropathy in the IDNT, irbesartan 300mg once daily provided significantly greater renoprotection than amlodipine 10mg once daily or placebo. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan is well tolerated in hypertensive patients, including those with type 2 diabetes and incipient or overt nephropathy. The overall incidence of adverse events with irbesartan was similar to that with placebo. Irbesartan was associated with a lower incidence of cough than enalapril and was not associated with ankle oedema or with any clinically significant drug interactions. In conclusion, irbesartan is a well tolerated and effective antihypertensive agent. It also slows the progression of renal disease in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. Thus, irbesartan is a valuable agent in the management of patients with these indications.

Angiotensin II↗