Candesartan Group Research Articles

Patient Adherence and Duration of Continuous Treatment With Various Arbs in Patients With Uncomplicated Arterial Hypertension in the USA Based on The Analysis of the Truven Health Analytics MarketScan Database.

To discuss two aspects that can be used to improve the adherence to therapy in patients with arterial hypertension (AH): 1) which of the angiotensin II receptor blockers (ARBs) provides the highest adherence rates; 2) how various factors influence adherence rates. An analysis of one of the world's largest clinical practice databases, Truven Health Analytics MarketScan (currently Merative MarketScan), was performed. The analysis included data on patients of both sexes aged 30 to 65 years who had been diagnosed with uncomplicated AH (at least once between March 1, 2012 and January 1, 2018) and prescribed monotherapy with one of ARBs. The exclusion criteria were heart failure and the treatment with two or more ARBs (simultaneously or sequentially) during the treatment period. Ultimately, the study included 717,099 patients with uncomplicated AH, who were divided into four groups based on the prescribed drug: azilsartan (n=4276), candesartan (n=6023), losartan (n=586,857), and valsartan (n=119,943). Adherence to treatment was evaluated by two parameters: duration of continuous therapy and medication possession ratio (MPR). The individual effect of each factor (specific ARB used for therapy, patient gender, age, initial ARB dose, patient co-payment per day of treatment) on the adherence to treatment was assessed using a regression analysis. The adherence to the ARB therapy was generally high. The MPR was the lowest in the azilsartan group and the highest in the candesartan group. However, the parameters that potentially influenced both the MPR and the duration of continuous therapy (patient's gender and age, initial ARB dose, co-payment size) differed significantly between the groups receiving different ARBs. The regression analysis showed that both adherence parameters and the duration of continuous therapy were higher in patients receiving candesartan than in patients receiving azilsartan, losartan or valsartan, when the effect on the adherence of other factors available for study (age, gender, initial dose of the drug, and the absolute size of co-payment for a day of therapy) was excluded. The lowest adherence to therapy was observed in the azilsartan treatment group (p<0.01). The study provided data for comparing the adherence of patients with uncomplicated AH to the therapy with different ARBs. Further study of adherence to treatment will provide additional data that will allow an optimal selection of drugs for the treatment of AH in patients with potentially poor adherence.

Sex-based differences in left ventricular mass reduction across angiotensin II receptor blockers in patients with heart failure with preserved or mildly reduced ejection fraction.

Although angiotensin II receptor blockers (ARBs) are more effective in women for either reduction of blood pressure or heart failure (HF), the gender disparities and the impact of class/drug effects on ARBs in relation to cardiac hypertrophy and HF remain unclear. We aimed to investigate the sex-based and drug-specific differences in left ventricular (LV) mass reduction with ARBs. We employed the cohort of 193 hypertensive patients with HF and an LV ejection fraction of ≥ 45% treated with azilsartan or candesartan once daily for 48 weeks as a sub-analysis of the J-TASTE trial. After exclusion of patients without LV mass data nor the drugs, 170 patients were finally enrolled (azilsartan: male, n = 43, female, n = 39 and candesartan: male, n = 52; female, n = 36). We investigated the sex-based differences of the primary endpoint of the change in LV mass as assessed by echocardiography from baseline to the end of the study (48 weeks), and the secondary endpoint of the incidence of the composite cardiovascular endpoint (death from cardiovascular disease or hospitalization for heart failure). In the male stratum, the ratio of patients with > 10% LV mass reduction at 48 weeks was higher in the azilsartan group than candesartan group (40 vs. 19%, p = 0.029). There was no significant difference in LV mass reduction between two groups in the female stratum. There were no differences of the onset of the secondary endpoints between male and female groups, and azilsartan and candesartan groups. The event-free survival rate of the composite cardiovascular endpoints tended to be lower in patients with ≤ 10% than > 10% LV mass reduction (95.3 vs. 100% at 48 weeks, log-rank p = 0.11). In patients with HF, the effectiveness of either azilsartan or candesartan in achieving > 10% LV mass reduction depends on sex. Male is more sensitive to azilsartan than candesartan to achieve cardiac hypertrophy in HF patients.

Long-Term Outcomes of Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction and Coexisting End-Stage Renal Disease.

Sacubitril/valsartan (Entresto) has proven therapeutic effects in heart failure (HF) patients, but its impact on those with advanced chronic kidney disease (CKD) remains unclear, particularly in HF patients with coexisting end-stage renal disease (ESRD). This study aims to assess the long-term survival of patients with heart failure with reduced ejection fraction (HFrEF) and coexisting ESRD treated with sacubitril/valsartan. A retrospective cohort study included 2,860 HFrEF and ESRD patients between January 2008 and December 2020. After propensity score matching, data from a sacubitril/valsartan group (n = 61) and a candesartan or valsartan group (n = 117) were analyzed. Patients on sacubitril/valsartan for at least 9 months had significantly lower 5-year all-cause mortality (39.3%) compared with the non-sacubitril/valsartan group (54.7%) (HR 0.46; 95% CI, 0.25-0.82; P = 0.0094). Left ventricular ejection fraction (LVEF) improvement after 3 years in the sacubitril/valsartan group (14.51 ±18.98) was significantly greater than the non-sacubitril/valsartan group (6.91 ±18.44) (P = 0.0408). Average hospitalizations in sacubitril/valsartan and non-sacubitril/valsartan groups were 1.39 and 0.97, respectively (incidence rate ratio, 1.59; 95% CI, 0.90-2.82; P = 0.1106). Sacubitril/valsartan treatment demonstrated significantly lower 5-year mortality rates and greater LVEF improvement in HFrEF patients with coexisting ESRD compared with candesartan or valsartan. These findings suggest that sacubitril/valsartan is a beneficial treatment option for this patient population.

Achieved dose and treatment discontinuation of candesartan in men and women with chronic heart failure: data from CHARM.

Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF)≤40%] in New York Heart Association class II-IV were randomized to candesartan or placebo. Every 2weeks, patients were up-titrated from 4 or 8, to16, to 32mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5±12.6mg in men and 20.7±12.9mg in women (P=0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person-years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person-years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P-value for all>0.05). There was no significant interaction between sex and treatment-related discontinuation for hypotension (P=0.520), an increase in creatinine (P=0.102), and hyperkalaemia (P=0.905). In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment-related discontinuation due to adverse events were also similar between men and women.

Long-Term Effects of Sacubitril/Valsartan After Chemotherapy for Breast Cancer in Patients With Chronic heart Failure

Background: As the survival of patients with malignant neoplasms is improving, the urgent need for cardioprotective agents to counteract toxic effects of chemotherapy is growing.Objective: To compare the cardioprotective efficacy of sacubitril/valsartan and candesartan in women with chronic heart failure and baseline reduced left ventricular ejection fraction (LVEF) during a 5-year prospective follow-up after chemotherapy for breast cancer.Materials and methods: In this randomized study, 127 women with chronic heart failure and reduced LVEF after radical surgical treatment of breast cancer received potentially cardiotoxic adjuvant polychemotherapy (fluorouracil+ doxorubicin + cyclophosphamide). In addition, the patients received sacubitril/valsartan at a dose of up to 97/103 mg twice daily (n = 63) or candesartan at a dose of up to 32 mg once daily (n = 65), and this treatment was monitored for 5 years.Results: The combination of sacubitril/valsartan was significantly superior to candesartan in improving left ventricular function and reducing the burden of ventricular arrhythmias and the risk of cardiovascular death (P = .039) at the long-term follow-up. Sacubitril/valsartan group and candesartan group did not differ in terms of mortality due to breast cancer progression or recurrence (P = .628).Conclusions: Sacubitril/valsartan can be considered an effective and safe option for protecting the cardiovascular system during potentially cardiotoxic polychemotherapy for breast cancer in patients with chronic heart failure and baseline reduced LVEF.

Candesartan Attenuates Vasculitis in a Mouse Model of Kawasaki Disease Induced by Candida albicans Water-Soluble Fraction.

The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment. Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan. The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFβ receptors. Measurement of the inflammatory cytokines IL-1β, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan. Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

Telmisartan and candesartan promote browning of white adipose tissue and reverse fatty liver changes in high fat diet fed male albino rats.

This work is designed to explore the possible mitigated effects of Telmisartan and Candesartan cilexetil on weight gain and fatty liver in high fat diet (HFD) fed rats. The HFD rat model was achieved with induction of NAFLD. For Seven weeks either telmisartan or candesartan were orally administered at doses of 5 and 10 mg/kg respectively once daily. The effects of both drugs were evaluated by measurements of rat's body weight, food intakes, length, body mass index (BMI), liver weight, inguinal and interscapular fat weights. In addition, we assayed lipid profile, liver functions tests, serum inflammatory cytokines, adipokine and leptin. Lastly, liver and adipose tissue histopathological structures were evaluated. at end of experiment, telmisartan and candesartan were highly effective in decreasing rat's body weight from (213.1±2.68 to 191.2±2.54 and 203.5±5.89 gm , respectively), BMI, liver weight, fat weights in addition reduced serum levels of lipid and liver enzymes. Also, inflammatory cytokines were reduced with repaired histopathological insults in liver by significantly damped NAFLD score from (6.5 ±0.17 to 1±0 and 4 ±0, respectively) and decreased areas of adipocytes from (21239.12 to 5355.7 and 11607.1 um2 , respectively). Telmisartan and candesartan have therapeutic potential against obesity and NAFLD induced by HFD in rats. All the previous indices showed more improvement in telmisartan than candesartan group.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient’s conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e′) (E/e′). Adjusted least-squares mean (LSM) change in E/e′ was − 0.8 (95% confidence interval [CI] − 1.49 to − 0.04) in the azilsartan group and 0.2 (95% CI − 0.49 to 0.94) in the candesartan group, providing the LSM differences of − 1.0 (95% CI − 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was – 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Effect of candesartan treatment on echocardiographic indices of cardiac remodeling in post-myocardial infarction patients.

Myocardial infarction has unfavorable effect on structural and functional properties of the myocardium, referred to as cardiac remodeling. Left ventricular mass, left ventricular mass index, and relative wall thickness are important predictors of cardiac remodeling. In this study, we investigated the effect of candesartan treatment in comparison with zofenopril treatment on echocardiographic indices of cardiac remodeling in post myocardial infarction patients. In this prospective study, patients who underwent successful percutaneous coronary intervention were randomly assigned to a candesartan or zofenopril treatment. After randomization, echocardiographic indices of cardiac remodeling including left ventricular mass, left ventricular mass index, and relative wall thickness were evaluated before the start of treatment along with 1- and 6-month follow-ups. According to our study, candesartan group showed significant reduction of estimated left ventricular mass and left ventricular mass index at 6-month follow-up visit compared to baseline values (199.53±38.51 g vs. 212.69±40.82 g; 99.05 g/m2 (90.00-116.5) vs. 106.0 g/m2 (96.0∼123.00), p<0.05, respectively). This trend was also observed in zofenopril group during the 6-month period (201.22±40.07 g vs. 207.52±41.61 g; 101.0 g/m2 (92.25-111.75.0) vs. 104.50 g/m2 (95.0∼116.75), p<0.05, respectively). Although both classes of drugs had favorable effects on post-myocardial infarction cardiac remodeling, the absolute benefit was more prominent in candesartan group as compared to zofenopril group (p<0.05). Our results suggest that candesartan treatment following myocardial infarction may potentially be useful in terms of improving post-myocardial infarction cardiac remodeling.

Protective Effect of Co Q10 and Candesartan on Bleomyycin Induced Lung Fibrosis in Rats

Fibrosis of the lungs is the final phase of many lung illnesses. Its characterized by excessive matrix production leading to the normal lung architecture destruction and eventually death. CoQ10 is an essential constituent of membrane oxidoreductase System. It is an intracellularly localized antioxidant&#x0D; &#x0D; enzyme that is endogenously synthesized in humans. CoQ10 protects cellular components from destruction by free radical-induced oxidative damage. candesartan is a selective antagonist of angiotensin II type 1 receptor (AT1) and is widely employed for treatment of hypertension. Most up to date research shows angiotensin II close involvement with damage and fibrosis process in tissues of organs of circulation.&#x0D; Objective: This animal study was designed to investigate the effect of Co Q10 and candesartan as antifibrotic agents against pulmonary fibrosis focusing on selected markers involved in pulmonary fibrosis.&#x0D; Materials and Method: 48 rats divided randomly into four groups, each consisting of 12 male rats. Group I: (Control group), the rats in this group received single injection of 0.2 ml normal saline via intratracheal route. Group II: (The BLM group), received BLM (8.3 U/kg) as a single dose via the intratracheal rout. Group III: (BLM+CoQ10 group) rats receive BLM (8.3 U/kg) as sulfate salt dissolved in 0.1 ml of normal saline via the intratracheal instillation concomitant with 100 mg/kg co Q 10 per day orally for 5 days before and 10 days after BLM injection. Group IV: (BLM+ candesartan group) rats receive BLM (8.3 U/kg) as sulfate salt dissolved in 0.1 ml of normal saline via the intratracheal instillation concomitant with (10 mg/kg) candesartan per day orally for 5 days before and 10 days after BLM injection. The studied serum biomarkers were glutathione, arachidonate 5 lipoxygenase in addition to histopathological examination using trichrome stain.&#x0D; Results: serum GSH concentration was lower in BLM group in comparison with the control group and the (BLM+ CoQ10) but this difference is not statistically significant. The serum GSH levels showed a significant(P&lt;0.05) elevation in (BLM+ Candesartan) group when compared with the levels in the BLM group. The serum ALOX5 concentration was significantly elevated in BLM group in comparison with the control group (P &lt; 0.05). The serum ALOX5 levels were highly significantly lower in (BLM +CoQ10) (P &lt; 0.01) and very highly significantly lower in the (BLM+ Candesartan) group (P &lt; 0.001) when comparing it with the levels in the BLM group. furthermore, histologically CoQ10 and candesartan showed reduction in the numbers of inflammation cells and a decrease in the damage to the lung architecture and fibrosis induced by bleomycin.&#x0D; Conclusion: CoQ10 and candesartan decrease pulmonary fibrosis induced by bleomycin in male rats.

Monitoring Kidney Function Through the Use of Candesartan, Telmisartan or Valsartan Antihypertensive Therapy towards Patients CKD

Chronic Kidney Disease (CKD) lower kidney function caused by an irreversible reduction in normal nephron function. Globally, CKD contributes to the cause of death. Activation of the Renin-Angiotensin-Aldosterone system is involved in the pathogenesis. ARBs have a cardiorenal protective effect. The purpose of this study was to determine the changes in kidney function with the use of Candesartan, Telmisartan or Valsartan antihypertensive therapies in CKD patients. This research method was a prospective observational cohort study looking at changes in kidney function (BUN and Serum Creatinine) at 1 and 6 months of using Antihypertensive Drugs Valsartan, Telmisartan, and Candesartan and tested by statistical analysis. The number of samples in this study was 72 patients which are 24 patients (Candesartan), 27 patients (Telmisartan), and 21 patients (Valsartan). The results showed that the Candesartan group experienced a decrease in average BUN of 0.13±0.85 mg/dl and serum creatinine of 0.004±0.09 mg/dl with independent t-test p=0.479 (p&gt;0.05), Serum Creatinine p= 0.809 (p&gt;0.05). The Telmisartan group experienced a decrease in average BUN of 4.74±5.16 mg/dl and serum creatinine of 0.33±0.20 mg/dl with Wilcoxon BUN test results p=0.000 (p&lt;0.05), Serum Creatinine p=0.000 (p&lt;0.05). In contrast, in the valsartan group, there was no change. So, it can be said that telmisartan has the highest effectiveness in kidney function (BUN and Serum Creatinine).

Incidence and Pattern of Aminotransferase Elevation During Anti-Hypertensive Therapy With Angiotensin-II Receptor Blockers

BackgroundAngiotensin type II receptor blockers (ARBs) are the most widely used anti-hypertensive drugs. This study aimed to elucidate the likelihood and pattern of ARB-induced liver injury in a hospital-based cohort.MethodsData of patients receiving fimasartan (n = 5,543), candesartan (n = 6,406), valsartan (n = 6,040), and losartan (n = 9,126) were retrieved from the clinical data warehouse of two tertiary hospitals. Patients with alanine aminotransferase (ALT) levels > 5 times the upper normal limit were assessed according to the Roussel Uclaf Causality Assessment Method (RUCAM).ResultsA total of 27,115 patients were enrolled, including 14,630 (54.0%) men, with a mean age of 64.6 years (standard deviation, 13.6). During 31,717 person-years of ARB therapy, serum ALT levels > 120 IU/L were found in 558 (2.1%) person-years, and levels > 200 IU/L were found in 155 (0.6%) person-years. The incidence of ALT elevation > 120 IU/L per 106 cumulative defined daily doses was 6.6, 3.6, 3.9, and 4.0 in the fimasartan, candesartan, valsartan, and losartan groups, respectively (P = 0.002). An ALT level > 200 IU/L with RUCAM score ≥ 6 was found in 20 patients, suggesting probable drug-induced liver injury for 11 (0.2%) patients receiving fimasartan, five (0.1%) receiving candesartan, four (0.1%) receiving valsartan, and none receiving losartan (P < 0.001).ConclusionApproximately 2% of patients receiving ARB therapy had significant ALT elevation (4.24/106 cumulative defined daily doses [cDDDs]), which was associated with probable ARB-related liver injury in 0.07% of patients (0.15/106 cDDDs). Elevation of ALT was more commonly associated with fimasartan than the other ARBs. Clinicians should be aware of the possibility of ARB-related ALT elevation in patients with unexplained chronic abnormal ALT.

Candesartan is associated with lower amyloid accumulation in non‐hypertensive prodromal Alzheimer’s disease

AbstractBackgroundWe have previously reported that candesartan improves executive function and memory in hypertensives with MCI. It is unclear if this drug has an effect on AD mechanisms or biomarkers.MethodThis randomized double‐blind clinical trial enrolled 77 non‐hypertensive participants (mean age: 68.1 years; n=48, 62% women; n=15, 20% African American) with prodromal AD. Individuals were screened and underwent cognitive and physical assessments, lumbar puncture, and blood collection at baseline, 6 months and 12 months. All participants were randomized to escalating doses of candesartan (up to 32 mg daily) or matching placebo. We investigated the target engagement of 1‐year treatment of candesartan vs placebo in MCI patients neither clinically diagnosed nor taking medication for hypertension, who have evidence of AD pathology. We assessed the effect of candesartan vs placebo on CSF AD biomarkers (amyloid‐β (Aβ)42, Aβ40, total tau, and phospho‐tau181 (p‐tau181)) analyzed on the Fujirebio Lumipulse platform using Fujirebio immunoassay reagents. Outcome analyses were conducted following an intent‐to‐treat approach with linear mixed models adjusted for group*time and cholinesterase inhibitors or memantine use.ResultParticipants randomized to candesartan developed fewer symptoms of hypotension compared to placebo (18% vs 26%) and there was no discontinuation from the trial due to adverse event from candesartan compared to placebo (0% vs 2.6%). After 1 year, the candesartan group had significantly higher CSF Aβ40 (‐1211.95, p‐value=0.009) and Aβ42 (‐49.51, p‐value=0.046) levels (Figure) vs placebo, reflecting lower brain amyloid accumulation. CSF Aβ42/Aβ40 showed a trend with an increased ratio in candesartan vs a decreased ratio in placebo, but did not reach statistical significance. Participants randomized to candesartan also showed a trend for decreases in CSF total tau and p‐tau181 and increases in Aβ42/total tau and Aβ42/p‐tau181 levels. Although the within groups were significant, the between groups did not reach significance for the tau‐based biomarkers.ConclusionIn this first human study in non‐hypertensive prodromal AD, candesartan treatment demonstrates target engagement and a reduction in brain amyloid accumulation compared to placebo. These findings may be useful in the prevention of AD or the slowing of disease progression. A larger trial is urgently needed for candesartan in AD.

Candesartan as a tentative treatment for COVID-19: A prospective non-randomized open-label study

BackgroundThis study aimed to investigate whether the addition of candesartan to the standard care regimen improved the outcome in patients with coronavirus 2019 (COVID-19). MethodsA prospective non-randomized open-label study was undertaken from May to August 2020 on 75 subjects (aged 18–70 years) hospitalized in Siloam Kelapa Dua Hospital. Uni- and multi-variable Cox regression analyses were performed to obtain hazard ratios (HRs). The primary outcomes were: (1) length of hospital stay; (2) time to negative swab; and (3) radiological outcome (time to improvement on chest X ray). ResultsNone of the 75 patients with COVID-19 required intensive care. All patients were angiotensin-receptor-blocker naïve. In comparison with the control group, the candesartan group had a significantly shorter hospital stay [adjusted HR 2.47, 95% confidence interval (CI) 1.16–5.29] after adjusting for a wide range of confounders, and no increased risk of intensive care. In the non-obese subgroup, the candesartan group had a shorter time to negative swab (unadjusted HR 2.11, 95% CI 1.02–4.36; adjusted HR 2.40, 95% CI 1.08–5.09) and shorter time to improvement in chest x ray (adjusted HR 2.82, 95% CI 1.13–7.03) compared with the control group. ConclusionCandesartan significantly reduces the length of hospital stay after adjustment for covariates. All primary outcomes improved significantly in the non-obese subgroup receiving candesartan.

Amelioration of lithiatic injury to renal tissue by candesartan and sodium thiosulfate in a rat model of nephrolithiasis.

AimNephrolithiasis is a chronic metabolic condition affecting 10% of population worldwide. The present study aimed to investigate the possible protective role of candesartan (CAND) and sodium thiosulfate (STS) in ameliorating ethylene glycol (EG) induced nephrolithiasis.MethodsOne hundred male Wistar rats were divided into five groups: Normal control group, nephrolithiasis (EG) group (1% EG in drinking water), Cystone (CYS) group (EG + 750 mg/kg CYS, orally, once daily), STS group (EG + 0.4 gm/kg STS, intraperitoneally, 3 times/week) and CAND group (EG + 70 μg/mL CAND in drinking water). Treatments and EG administration commenced on the same day and continued for 28 days. CYS was used as reference drug. Urine, blood, and renal tissues were collected at the end of the experiment for assessment of kidney function tests (serum creatinine and urea), urinary (8-hydroxydeoxyguanosine (8-OHdG), calcium and oxalate), inflammatory and oxdative stress biomarkers (transforming growth factor beta (TGF-β), osteopontin (OPN) and ratio of reduced glutathione to oxidized glutathione (GSH/GSSG)) in renal tissue.ResultsSerum (creatinine and urea), urinary (8-OHdG and oxalate) and renal (OPN and TGF-β) were significantly reduced in CAND and STS groups compared to EG group. Furthermore, renal GSH/GSSG and urinary calcium were significantly increased in CAND and STS groups compared to EG group. Histopathological results support the biochemical findings; CAND and STS groups showed less retention of crystals and necrotic damage in kidney. Also, microscopic examination of urine revealed less crystal for CAND and STS groups.ConclusionCandesartan and sodium thiosulfate exhibited protective effect against nephrolithiasis.

Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial

Introduction: Angiotensin receptor blockers (ARBs) are preferably used in hypertensive patients with CKD. Azilsartan is a strong antihypertensive ARB, but its antiproteinuric effects are not well understood. We compared the antiproteinuric effect of azilsartan and candesartan in CKD patients in an open-label, randomized, crossover trial. Methods: A total of 111 patients were treated with 20 mg of azilsartan daily for 2 months as a run-in period. After the run-in period, patients were randomized into 2 arms and received either 20 mg of azilsartan or 8 mg of candesartan daily for 3 months in a crossover trial. The primary outcome was the percent change in urinary protein-to-Cr ratio (UPCR). Results: Ninety-five patients completed the trial. The mean age was 64.3 years. The estimated glomerular filtration rate (eGFR) and UPCR were 41.5 mL/min/1.73 m² and 1.8 g/gCr, respectively. The baseline systolic and diastolic blood pressures were 131.4 and 71.0 mm Hg, respectively. The mean percent change in the UPCR was −3.8% in the azilsartan group and 30.8% in the candesartan group at the 1st endpoint (p = 0.0004), and 6.1% in the azilsartan group and 25.8% in the candesartan group at the 2nd (final) endpoint (p = 0.029). The incidence of adverse events, including eGFR levels and serum potassium levels, was not significantly different between the groups. Conclusion: A 20 mg azilsartan dose had potent antiproteinuric effects compared with an 8 mg candesartan dose, without an increase in adverse events. Azilsartan may provide renal protection in addition to antihypertensive effects in CKD patients.

Effect of Candesartan and Ramipril on Liver Fibrosis in Patients with Chronic Hepatitis C Viral Infection: A Randomized Controlled Prospective Study

Objective: This study aimed at evaluating the effects of candesartan and ramipril on liver fibrosis in patients with chronic hepatitis C. Methods: This randomized controlled prospective study involved 64 patients with chronic hepatitis C and liver fibrosis. Participants were randomized into 3 groups: group I (control group; n = 21), members of which received traditional therapy only; group 2 (ramipril group; n = 21), members of which received traditional therapy plus 1.25 mg/d oral ramipril; and group 3 (candesartan group; n = 22), members of which received traditional therapy plus 8 mg/d oral candesartan. Patients were assessed at baseline and 6 months after intervention through measuring of liver stiffness (Fibro-Scan; Echosens, Paris, France); evaluation of the serum levels of hyaluronic acid and transforming growth factor beta-1; and calculation of indices of liver fibrosis, including fibrosis index based on the 4 factors and aspartate transaminase-to-platelet-ratio index. Data were analyzed using paired t test and 1-way ANOVA followed by Tukey's honest significant difference test for multiple pairwise comparisons. Results: At baseline, the 3 study groups were statistically similar in demographic and laboratory data. After treatment, the 3 study groups showed significant decrease in liver stiffness, serum levels of hyaluronic acid and transforming growth factor beta-1, and indices of liver fibrosis compared with baseline data (P < 0.001). Six months after treatment, patients taking ramipril and candesartan showed significant improvement in all measured parameters compared with the control group. Additionally, the candesartan-treated group showed significant decrease in liver stiffness, biomarkers, and indices of liver fibrosis compared with ramipril recipients. Conclusions: The administration of ramipril and candesartan in patients with chronic hepatitis C with hepatic fibrosis was well tolerated and effective in improving liver fibrosis. angiotensin II receptor 1 (AT1) antagonist candesartan maintained antifibrotic effects more effectively than ramipril and may represent a safe and effective therapeutic strategy for liver fibrosis in patients with chronic liver diseases. ClinicalTrials.gov identifier: NCT03770936. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX) © 2022 Elsevier HS Journals, Inc.

Sacubitril/valsartan versus candesartan in women with heart failure receiving adjuvant therapy for breast cancer - is there any antiarrhythmic effect?

Purpose. To compare the effects of sacubitril/valsartan and candesartan on the occurrence and course of heart arrhythmias in the standard treatment of heart failure (HF) in patients with breast cancer receiving anthracycline antibiotics as part of adjuvant polychemotherapy. Methods. The study involved 127 women aged 53 to 65 who received radical surgical and subsequent treatment for breast cancer in the MAMME clinic in Krasnodar in 2017-2020. Patients were prescribed adjuvant polychemotherapy, including anthracyclines, from 6 cycles. After randomization, standard HF therapy was carried out simultaneously with chemotherapy using sacubitril/valsartan (n=63) or candersartan (n=64). Initially, after the first, third and last courses of special cancer therapy, the heart rate was assessed using standard electrocardiography, 24-hour Holter monitoring of the electrocardiogram, transthoracic echocardiography, a 6-minute walk test were performed, and the level of the N-terminal pro-B type natriuretic peptide and high-sensitivity cardiac troponin I, the Minnesota Quality of Life Questionnaire for patients with chronic HF was completed.Results. According to the 24-hour Holter monitoring of the electrocardiogram, the burden of ventricular premature contraction significantly decreased in the sacubitril/valsartan group (p=0.018), but not in candesartan group (p=0.326). The proportion of patients with persisting episodes of unstable ventricular tachycardia was also significantly reduced in patients randomized to take sacubitril/valsartan (p=0.027), but practically did not change in the candesartan group (p=0.785). Physical exercise tolerance, a 6-minute walk distance, and a quality of life indicator significantly improved only in the sacubitril/valsartan group. According to echocardiography, sacubitril/valsartan improved systolic function of the left ventricle, and candesartan only prevented its decline under the influence of the damaging effects of chemotherapy.Conclusion. The efficacy and safety of treating patients who received cardiotoxic adjuvant chemotherapy for breast cancer, a decrease in the burden of ventricular arrhythmias, noted in the sacubitril/valsartan group, were a consequence of the intensification of treatment for HF. The cardiotoxic effect of anthracyclines can be overcome thanks to the pronounced positive neurohumoral effects of modern pharmacotherapy of HF using sacubitril/valsartan, which leads to a limitation of myocardial remodeling.

Protective Effects of Statin and Angiotensin Receptor Blocker in a Rat Model of Doxorubicin- and Trastuzumab-Induced Cardiomyopathy

Chemotherapy has led to improved survival in patients with breast cancer; however, it is associated with an increased risk of cardiac dysfunction and heart failure. We investigated the protective effects of rosuvastatin and candesartan, alone and in combination, in a doxorubicin- and trastuzumab-induced rat model of cardiomyopathy. Forty-two rats were allocated into six groups (G1-G6): G1, control; G2, doxorubicin only; G3, doxorubicin +trastuzumab; G4, doxorubicin+trastuzumab+rosuvastatin; G5, doxorubicin+trastuzumab+candesartan; and G6, doxorubicin+trastuzumab+rosuvastatin+candesartan. Doxorubicin and trastuzumab were sequentially administered for 28days. Left ventricular end-systolic dimension and longitudinal strain (LS) were assessed via echocardiography. Left ventricular (LV) performance was evaluated using a microcatheter in the LV apex on day 28. Blood for biomarker analysis was collected from the inferior vena cava before sacrifice. Doxorubicin in combination with trastuzumab increased the LV end-systolic dimension but worsened LS compared with the control group (all P<.05). The level of C-reactive protein was lower in the rosuvastatin treatment group (P=.007) than in the controls but not in the candesartan treatment group. Both rosuvastatin and candesartan attenuated the increase in glutathione. Candesartan treatment improved+dP/dt (P=.011), whereas rosuvastatin did not. In the combination treatment group, the worsening of LS was significantly attenuated compared with that in either the rosuvastatin or candesartan group (all P<.05). In a rat model of doxorubicin- and trastuzumab-induced cardiomyopathy, rosuvastatin alleviated systemic inflammation, while candesartan improved LV performance. Combination therapy with rosuvastatin and candesartan demonstrated additional preventive effects on myocardial strain. The protective mechanisms of rosuvastatin and candesartan appear to be different but complementary in chemotherapy-induced cardiomyopathy.

Effects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment

Observational studies have suggested that angiotensin receptor blockers are associated with a unique cognitive protection. It is unclear if this is due to reduced blood pressure (BP) or angiotensin receptors type 1 blockade. To determine neurocognitive effects of candesartan vs lisinopril in older adults with mild cognitive impairment (MCI). This randomized clinical trial included participants aged 55 years or older with MCI and hypertension. Individuals were withdrawn from prior antihypertensive therapy and randomized in a 1 to 1 ratio to candesartan or lisinopril from June 2014 to December 2018. Participants underwent cognitive assessments at baseline and at 6 and 12 months. Brain magnetic resonance images were obtained at baseline and 12 months. This intent-to-treat study was double-blind and powered for a sample size accounting for 20% dropout. Data were analyzed from May to October 2019. Escalating doses of oral candesartan (up to 32 mg) or lisinopril (up to 40 mg) once daily. Open-label antihypertensive drug treatments were added as needed to achieve BP less than 140/90 mm Hg. The primary outcome was executive function (measured using the Trail Making Test, Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research tool) and secondary outcomes were episodic memory (measured using the Hopkins Verbal Learning Test-Revised) and microvascular brain injury reflected by magnetic resonance images of white matter lesions. Among 176 randomized participants (mean [SD] age, 66.0 [7.8] years; 101 [57.4%] women; 113 [64.2%] African American), 87 were assigned to candesartan and 89 were assigned to lisinopril. Among these, 141 participants completed the trial, including 77 in the candesartan group and 64 in the lisinopril group. Although the lisinopril vs candesartan groups achieved similar BP (12-month mean [SD] systolic BP: 130 [17] mm Hg vs 134 [20] mm Hg; P = .20; 12-month mean [SD] diastolic BP: 77 [10] mm Hg vs 78 [11] mm Hg; P = .52), candesartan was superior to lisinopril on the primary outcome of executive function measured by Trail Making Test Part B (effect size [ES] = -12.8 [95% CI, -22.5 to -3.1]) but not Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research score (ES = -0.03 [95% CI, -0.08 to 0.03]). Candesartan was also superior to lisinopril on the secondary outcome of Hopkins Verbal Learning Test-Revised delayed recall (ES = 0.4 [95% CI, 0.02 to 0.8]) and retention (ES = 5.1 [95% CI, 0.7 to 9.5]). These findings suggest that in older adults with MCI, 1-year treatment with candesartan had superior neurocognitive outcomes compared with lisinopril. These effects are likely independent of the BP-lowering effect of candesartan. ClinicalTrials.gov Identifier: NCT01984164.