Safety Of Irbesartan Research Articles

Short-term and long-term efficacies of combined use of irbesartan and calcitriol for the treatment of IgA nephropathy

Purpose: To determine the efficacy and safety of irbesartan plus calcitriol in the treatment of IgA nephropathy, and its effect on inflammatory injury and complement systemMethods: Differences in renal function, inflammatory response, immune function, complement factor levels, clinical efficacy, and incidence of adverse reactions between IgA nephropathy patients treated with irbesartan (control, n = 50) and those treated with irbesartan + calcitriol (study group, n = 50) after 2 and 12 months, were retrospectively analyzed. As treatment progressed, protein in 24-h urine, and creatinine and BUN in both groups were gradually reduced.Results: The serum levels of complement factors C1q and C3 in both groups gradually increased, while C4 level gradually decreased. Relative to pre-treatment, at 2- and 12-months post-treatment, serum levels of C1q and C3 in both groups were raised, while C4 level decreased (p < 0.05). Relative to control, serum C1q and C3 in the study group were raised, while C4 level was decreased (p < 0.05). Relative to the control group, total treatment effectiveness in the study group increased at 2- and 12- months post-treatment (p < 0.05). There was no significant difference in the incidence of adverse reactions between the control and study groups during the treatment.Conclusion: Treatment with irbesartan + calcitriol significantly improves renal function in patients with IgA nephropathy, reduces inflammatory response, and improves immune function and clinical effectiveness with high safety profile. More clinical trials should be carried out to validate the findings of this study.

Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis

BackgroundChemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance.MethodsWe established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editing, sphere formation assays, iron assays and luciferase assays were conducted to elucidate the mechanism.ResultsHigh-throughput drug screening of chemotherapy-resistant PDOs identified irbesartan, an angiotensin ‖ type 1 (AT1) receptor antagonist, which could synergistically enhance the ability of chemotherapy to kill PDAC cells. In vitro and in vivo validation using PDO, PDX and KPC mouse models showed that irbesartan efficiently sensitized PDAC tumors to chemotherapy. Mechanistically, we found that irbesartan decreased c-Jun expression by inhibiting the Hippo/YAP1 pathway and further overcame chemotherapy resistance in PDAC. We also explored c-Jun, a potential target of irbesartan, which can transcriptionally upregulate the expression of key genes involved in stemness maintenance (SOX9/SOX2/OCT4) and iron metabolism (FTH1/FTL/TFRC). More importantly, we observed that PDAC patients with high levels of c-Jun expression demonstrated poor responses to the current standard chemotherapy regimen (gemcitabine plus nab-paclitaxel). Moreover, patients with PDAC had significant survival benefits from treatment with irbesartan plus a standard chemotherapy regimen in two-center retrospective clinical cohorts and patients with high c-Jun expression exhibited a better response to combination chemotherapy.ConclusionsIrbesartan could be used in combination with chemotherapy to improve the therapeutic efficacy in PDAC patients with high levels of c-Jun expression. Irbesartan effectively inhibited chemotherapy resistance by suppressing the Hippo/YAP1/c-Jun/stemness/iron metabolism axis. Based on our findings, we are designing an investigator-initiated phase II clinical trial on the efficacy and safety of irbesartan plus a standard gemcitabine/nab-paclitaxel regimen in the treatment of patients with advanced III/IV staged PDAC and are hopeful that we will observe patient benefits.

Клинико-фармакологические особенности и место ирбесартана в лечении сердечно-сосудистых заболеваний

Irbesartan belongs to a group of angiotensin II receptor blockers that are used worldwide for the treatment of patients with hypertension, type 2 diabetes, and impaired renal function. Irbesartan can be administered alone or in combination with other antihypertensive drugs (for example, hydrochlorothiazide), if blood pressure control cannot be achieved with monotherapy. The mechanism of action of Irbesartan is mainly due to the selective blockade of AT1 receptors and, as a consequence, a decrease in the vasopressor effect of angiotensin II. The review article summarizes pharmacokinetic and pharmacodynamic properties and clinical data on the tolerability and safety of Irbesartan.

Efficacy of irbesartan in arterial hypertension and metabolic syndrome

The paper gives the data of Russian guidelines for the diagnosis and approaches to treating metabolic syndrome. It considers the choice of antihypertensive drugs in the treatment of hypertensive patients with metabolic syndrome. The benefits of angiotensin II receptor blockers are shown. The results of a number of trials evaluating the efficacy and safety of irbesartan used to manage arterial hypertension in metabolic syndrome are analyzed.

Comparison of the Efficacy and Safety of Irbesartan and Olmesartan in Patients With Hypertension (EARTH Study)

Fifty-four patients were randomly divided into irbesartan and olmesartan groups. Blood pressure (BP) was significantly decreased in all patients at 12 weeks. In particular, BP in patients who initially received irbesartan showed significant reductions. The equality of variance of BP in the irbesartan group was significantly smaller than that in the olmesartan group at 12 weeks. Blood concentrations of adiponectin were significantly increased in the irbesartan group at 12 weeks. Log [pentraxin-3] in the irbesartan group were significantly decreased. In conclusion, the ability of irbesartan to reduce BP is comparable to that of olmesartan with equivalent safety.

The efficacy and safety of irbesartan in primary hypertension even if a dose is missed: Results from the NO PROBLEM Study

Objectives. This study aimed to demonstrate that irbesartan is successful in reducing diastolic blood pressure (BP) even following a missed dose after 6–8-weeks’ treatment as measured by 24-hour ambulatory BP monitoring (ABPM). Methods. Eighty-eight patients (64 females, mean age: 53.4 ± 10.6 years) with primary hypertension were included in this national, single-center, single-arm, open-label, prospective clinical study. Irbesartan (150 or 300 mg/day) was administered for 8 weeks. All patients were asked to cease treatment for 1 day during weeks 6–8. Changes in diastolic and mean 24-hour BP on the day of cessation and diastolic BP values during visits were efficacy parameters. Adverse events were also recorded. Results. Systolic, diastolic, and mean BP values measured via ABPM before and on the day of a missed dose did not differ significantly. Irbesartan effectively controlled BP of the patients. BP normalization rates were 54% for 150 mg/day irbesartan only and 77% for both doses (150 or 300 mg/day) of irbesartan. None of the patients experienced serious adverse events throughout the study period. Conclusions. Irbesartan is successful and safe in the control of BP levels even following a missed dose at the end of a 6–8-week treatment period.

Antihypertensive efficacy and safety of irbesartan compared with the best perceived therapy in a population of 9331 hypertensive patients. results of the PACTE study

Antihypertensive efficacy and safety of irbesartan compared with the best perceived therapy in a population of 9331 hypertensive patients. results of the PACTE study

Evaluation of long-term efficacy and tolerability of irbesartan in elderly hypertensive patients with renal impairment in an open-label study

Background: Hypertension, left untreated, can lead to serious complications, including stroke myocardial infarction, and renal failure. Because lowering blood pressure correlates with slowing of renal disease progression, the control of hypertension in the presence of renal disease is essential. Objective: We evaluated the efficacy, tolerability, and safety of irbesartan alone or in combination with other antihypertensive agents in elderly patients with hypertension and chronic renal insufficiency. Methods: Patients > 65 years of age with hypertension (sitting diastolic blood pressure [SiDBP] 90–115 mm Hg) and chronic renal sufficiency that was mild (creatinine clearance [CrCL] 30–60 mL/min per 1.73 m 2) or moderate to severe CrCL 10–29 mL/min per 1.73 m 2) were enrolled. After a 3-week placebo run-in period, irbesartan was administered for 12 months at 150 mg/d. After 4 weeks of therapy, patients whose blood pressure was not adequately controlled (ie, SiDBP ≥90 mm Hg or <5 mm Hg decrease from baseline) had an additional antihypertensive agent added to their daily irbesartan regimen; dosage adjustment of the second drug was permitted after 2 weeks to optimize blood pressure control. Twenty-four-hour CrCL was determined, and renal clearance studies of inulin and p-aminohippurate were performed in a subset of patients. Results: A total of 32 patients (21 men, 11 women; mean age, 70.4 years) were enrolled. Thirty patients had mild renal insufficiency (mean CrCL, 44.45 mL/min per 1.73 m 2) and 2 patients had moderate to severe renal insufficiency (mean CrCL 21.32 mL/min per 1.73 m 2). Trough sitting blood pressures were reduced at the end of the first week of treatment in all groups. After 8 weeks, 12 weeks, and 1 year of treatment, the mean reductions in systolic blood pressure (SBP)/DBP were −11.9/−8.7 mm Hg, −10.8/−9.4 mm Hg, and −14.7/−12.1 mm Hg, respectively, in patients with mild renal insufficiency and −7.7/−6.3 mm Hg, −13.1/−11.8 mm Hg, and −14.1/−10.6 mm Hg in patients with moderate to severe renal insufficiency. CrCL, glomerular filtration rate, and effective renal plasma flow, as measured in a subset of 11 patients, were stable. Treatment was discontinued for 3 patients because of a clinical adverse event or laboratory parameter abnormality. Hyperkalemia (>6 mEq/L) requiring discontinuation of irbesartan occurred in 1 patient with moderate to severe renal insufficiency. Conclusion: The results of this study suggest that irbesartan, as monotherapy (150 mg once daily) or in combination with other antihypertensive drugs, is effective in reducing blood pressure in elderly hypertensive patients with chronic renal impairment and that irbesartan regimens are well tolerated in this population.

A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: The MAPAVEL study

Background: When blood pressure (BP)—lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II—receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients (>200) with essential hypertension. Objective: This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. Methods: This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90–109 mm Hg or systolic BP [SBP] 140–179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP ≥85 mm Hg, as measured by ABPM between 10 am and 8 pm, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was ≥90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading <140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of ≥10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP <130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP ≥5 mm Hg at 12 weeks were considered responders, independent of clinic values. Results: A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was ∼52.0% female and 48.0% male, with a mean (±SD) age of 52.7 ± 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 ± 8.8 mm Hg irbesartan vs 12.4 ± 7.4 mm Hg enalapril; SBP, 19.0 ± 14.1 mm Hg vs 17.5 ± 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 ± 8.5 mm Hg vs 8.8 ± 8.5 mm Hg; SBP, 14.7 ± 14.7 mm Hg vs 12.6 ± 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). Conclusions: As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.

Multicenter, double-blind, randomized study comparing efficacy and safety of irbesartan versus enalapril assessed by ABPM in mild-to-moderate hypertension

Multicenter, double-blind, randomized study comparing efficacy and safety of irbesartan versus enalapril assessed by ABPM in mild-to-moderate hypertension

The efficacy and safety of irbesartan in treating essential hypertension

Background:Irbersatan, an orally active antihypertensive agent, effectively reduce blood pressure by directly blocking angiotensin II receptors without any significant adverse effects. The purpose of this study is to evaluate the efficacy and safety of irbesartan in patients with mild to moderate hypertension. Methods: This study enrolled 83 patients who had diastolic pressure above 95 mmHg and below 110 mmHg on two measurements. Sixty eight patients were administered 150mg of irbesartan, an angiotensin II receptor blocker, daily for four weeks as an initial dosage. If the sitting diastolic pressure was equal to or greater than 90 mmHg after a 4 week treatment period, the dosage was doubled until the end of 8 weeks. Baseline pressures, antihypertensive effect, side effects, laboratory findings were compared before and after treatment. Results: Fourty two patients out of 53 patients having completed this study showed decreased blood pressure equal to or more than 5 mmHg of the sitting diastolic pressure (response rate=79%). Twenty one patients out of 53 patients showed normalized blood pressure below 90 mmHg of the sitting diastolic pressure (normalization rate=40%). The extent of decrease in diastolic and systolic blood pressure after eight week treatment was an average 11.7±10.1 mmHg and 16.3±18.9 mmHg, respectively (p<0.05). Nineteen ontoward side effects was observed in 17 patients out of 68 patients with medication (frequency of ontoward effects=25%). Only one case with headache was considered to be related to the medication. Abnormal laboratory findings were observed in eight patients, and only one case with elevation of bilirubin and ALT levels was considered to be related to the medication. Conclusion:In conclusion, irbesartan is a safe and effective antihypertensive drug in patients with mild to moderate hypertension with tolerable side effects. (Korean Circulation J 2000; 30(3):318-325)

The efficacy and safety of irbesartan in patients with essential hypertension in community hospitals of Catalonian

The efficacy and safety of irbesartan in patients with essential hypertension in community hospitals of Catalonian

The antihypertensive efficacy and safety of Irbesartan compared with amlodipine for the treatment of mild-to-moderate hypertension.

The antihypertensive efficacy and safety of Irbesartan compared with amlodipine for the treatment of mild-to-moderate hypertension.

Safety of irbesartan in the treatment of mild to moderate systemic hypertension

Nine multicenter, randomized, placebo-controlled studies were conducted to evaluate the safety and tolerability of the angiotensin II subtype 1 receptor blocker (AT 1 blocker) irbesartan for the treatment of mild to moderate hypertension. After a 4- to 5-week placebo lead-in phase, patients were randomized to 4 to 12 weeks of double-blind therapy with either placebo (n = 641) or irbesartan (n = 1,965) at doses of 1 to 900 mg orally. All doses of irbesartan were well tolerated with no evidence of dose-related adverse effects. Across the full recommended clinical dose range, although not statistically significantly different, irbesartan use was associated with a lower incidence of adverse events, serious adverse events, and discontinuations due to adverse events compared with placebo. No clinically significant or unexpected changes in laboratory analyses were observed. Withdrawal of irbesartan therapy did not result in rebound hypertension or clinically important adverse events. Thus, irbesartan use in hypertensive patients was associated with a placebo-like safety and tolerability profile.

Comparison of the Angiotensin II Receptor Antagonist Irbesartan With Atenolol for Treatment of Hypertension

In this multicenter, double-blind study, the antihypertensive efficacy and safety of irbesartan were compared with those of atenolol in patients with mild-to-moderate hypertension. Following a 4- to 5-week placebo lead-in period, 231 patients with seated diastolic blood pressure (SeDBP) 95-110 mmHg were randomized to irbesartan 75 mg or atenolol 50 mg once daily for 24 weeks. Doses were doubled at Week 6 for SeDBP > or = 90 mmHg. At Week 12, or anytime thereafter, doses were doubled for SeDBP > or = 90 mmHg if not done at Week 6, and hydrochlorothiazide and then nifedipine were added. Efficacy was determined by change from baseline in blood pressure and by therapeutic response rates. Safety was assessed by monitoring adverse events (AEs). Both treatments significantly lowered blood pressure from baseline. There were no significant differences between treatment groups with respect to blood pressure changes or therapeutic response. Atenolol significantly reduced seated heart rate compared with irbesartan at Week 12. The incidences of serious AEs and discontinuations due to AEs were approximately twice as high in the atenolol group compared with the irbesartan group. Thus, in comparison to atenolol, irbesartan < or = 150 mg provided at least equivalent blood pressure control while demonstrating an excellent safety and tolerability profile.