Candesartan In Hypertensive Patients Research Articles

Cost-effectiveness analysis of amlodipine and candesartan in the inpatient setting at Mataram University Hospital in Indonesia, 2021

Background: Hypertension requires ongoing treatment, which could be costly. There are different single-drug therapy options available, such as amlodipine or candesartan, which have varying costs. Objective: This study aimed to analyse the cost-effectiveness of amlodipine and candesartan in hypertensive patients by determining the Average Cost Effectiveness Ratio (ACER) and Incremental Cost Effectiveness Ratio (ICER) ratios from a hospital perspective. Method: This study used probability sampling of retrospective data from 2021 for the analysis. All inpatients who were given single therapy with amlodipine of 10 mg or candesartan of 16 mg were included. Direct medical costs were collected, including medicine and room costs, doctor visits, medical procedures, labour and administration. The effectiveness of the therapy was measured by blood pressure reduction from each therapy. ACER and ICER analyses were conducted to determine the most cost-effective therapy. Result: A total of 18 samples met the inclusion criteria, 14 patients received amlodipine therapy, and four received candesartan therapy. The results showed that the cost-effectiveness of antihypertensive therapy with amlodipine and candesartan, as measured by ACER, was IDR 74,851.15 and IDR 87,809.25, respectively. The ICER value obtained was IDR 362,768. Conclusion: The results may suggest that amlodipine is more cost-effective than candesartan.

Genetic variants of GRK4 influence circadian rhythm of blood pressure and response to candesartan in hypertensive patients

ABSTRACT Background: Genetic variants of coding genes related to blood pressure regulation participate in the pathogenesis of hypertension and determines the response to specific antihypertensive drugs. G protein-coupled receptor kinase 4 (GRK4) and its variants are of great importance in pathogenesis of hypertension. However, little is known about role of GRK4 variants in determine circadian rhythm of blood pressure and response to candesartan in hypertension. The aim of this study was to analyze the correlation of GRK4 variants and circadian rhythm of blood pressure, and to explore their effect on antihypertensive efficiency of candestartan. Methods: In this study, a total of 1239 cases were eligible, completed ambulatory blood pressure monitoring (ABPm) observation and exon sequencing of G protein-coupled receptor kinase 4 (GRK4). ABPm was obtained before and after 4-week treatment of candesartan. Diurnal variation of systolic blood pressure and antihypertensive effect of candesartan were then assessed. Results: Compared to GRK4 wild type (GRK4-WT), patients with GRK4 variants were more likely to be non-dippers (odds ratio (OR) 6.672, 95% confidence interval (CI) 5.124–8.688, P < .001), with GRK4 A142V (OR 5.888, 95% CI 4.332–8.003, P < .001), A486V (OR 7.102, 95% CI 5.334–9.455, P < .001) and GRK4 R65L (OR 3.273, 95% CI 2.271–4.718, P < .001), respectively. Correlation analysis revealed that non-dippers rhythm of blood pressure were associated with GRK4 variants (r = .420, P < .001), with GRK4 A142V (r = .416, P < .001), A486V (r = .465, P < .001) and GRK4 R65L (r = .266, P < .001), respectively. When given 4-week candesartan, patients with GRK4 variants showed better antihypertensive effect as to drop in blood pressure (24 h mSBP, 21.21 ± 4.99 vs 12.34 ± 4.78 mmHg, P < .001) and morning peak (MP-SBP, 16.54 ± 4.37 vs 11.52 ± 4.14 mmHg, P < .001), as well as greater increase in trough to peak ratio (SBP-T/P, .71 ± .07 vs .58 ± .07, P < .001) and smoothness index (SBP-SI, 1.44 ± .16 vs 1.17 ± .11, P < .001) than those with GRK4 WT. Conclusion: This study indicates that hypertensive patients with GRK4 variants are more likely to be non-dippers. What’s more, patients with GRK4 variants possess a significantly better antihypertensive response to candesartan than those with GRK4 WT.

Efficacy of the combination of amlodipine and candesartan in hypertensive patients with coronary artery disease: A subanalysis of the HIJ-CREATE study

BackgroundThe effects of the combination of angiotensin II receptor blocker (ARB) plus dihydropyridine calcium channel blockers (DHP-CCBs), which is known as a potent antihypertensive drug regimen, on cardiovascular events remain unclear. ObjectiveThe purpose of this post hoc subgroup analysis was to compare the incidence of major adverse cardiovascular events (MACE) of patients treated with candesartan and amlodipine with that of those with candesartan and non-amlodipine CCBs in hypertensive patients with coronary artery disease (CAD). MethodsHIJ-CREATE was a multicenter, prospective, randomized, controlled study that compared the effects of candesartan-based with those of non-ARB-based standard therapy on MACE in 2049 hypertensive patients with CAD. In the candesartan group, a total of 335 patients were treated with DHP-CCBs (amlodipine: 170 and non-amlodipine-CCBs: 165) at the baseline. In this sub-analysis, we compared, among the participants allocated to candesartan regimen, the long-term effects of amlodipine and non-amlodipine CCBs that were concomitantly given with ARB, although the choice of CCB was not randomized. ResultsThe median follow-up was 3.9 years. Treatment using amlodipine with candesartan reduced the risk of MACE by 38% (hazard ratio, 0.62; 95% confidence interval, 0.41–0.94, p=0.025), as compared to patients treated with non-amlodipine-CCBs and candesartan. In a multivariate analysis, combination therapy of candesartan with amlodipine was an independent predictor of reduced risk of MACE. ConclusionsThe results suggest that the combination of amlodipine and candesartan is more beneficial in reducing MACE in hypertensive patients with CAD compared to non-amlodipine-DHP-CCBs in combination therapy with candesartan. Further investigation in larger-scale prospective randomized studies is required to reach any conclusion as to the superiority of combination therapy of candesartan with amlodipine.

Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure

BackgroundAngiotensin receptor blockers (ARBs) are reported to provide direct protection to many organs by controlling inflammation and decreasing oxidant stress in patients without arteriosclerosis. This study aimed to evaluate (1) whether an ARB (candesartan) decreases values for inflammatory parameters in hypertensive patients with type 2 diabetes mellitus of long duration accompanied by arteriosclerosis and (2) whether there any predictors of which patients would receive the benefits of organ protection by candesartan.MethodsWe administered candesartan therapy (12 mg daily) for 6 months and evaluated whether there was improvement in serum inflammatory parameters high molecular weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) in serum and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). We then analyzed the relationship between the degree of lowering of blood pressure and inflammatory factors and the relationship between pulse pressure and inflammatory factors. Finally, we analyzed predictive factors in patients who received the protective benefit of candesartan.ResultsAfter 6 months of treatment, significant improvements from baseline values were observed in all patients in HMW-ADN and PAI-1 but not in Hs-CRP, VCAM-1 and U-8-OHdG. Multilinear regression analysis was performed to determine which factors could best predict changes in HMW-ADN and PAI-1. Changes in blood pressure were not significant predictors of changes in metabolic factors in all patients. We found that the group with baseline pulse pressure <60 mmHg had improved HMW-ADN and PAI-1 values compared with the group with baseline pulse pressure ≥ 60 mmHg. These results suggest that pulse pressure at baseline could be predictive of changes in HMW-ADN and PAI-1.ConclusionsCandesartan improved inflammatory parameters (HMW-ADN and PAI-1) in hypertensive patients with type 2 diabetes mellitus of long duration independent of blood pressure changes. Patients with pulse pressure <60 mmHg might receive protective benefits by candesartan.Trial registrationUMIN000007921

Role of angiotensin II in plasma PAI-1 changes induced by imidapril or candesartan in hypertensive patients with metabolic syndrome

To evaluate the relationship between plasma plasminogen activator inhibitor-1 (PAI-1) and angiotensin II (Ang II) changes during treatment with imidapril and candesartan in hypertensive patients with metabolic syndrome. A total of 84 hypertensive patients with metabolic syndrome were randomized to imidapril 10 mg or candesartan 16 mg for 16 weeks. At weeks 4 and 8, there was a dose titration to imidapril 20 mg and candesartan 32 mg in nonresponders (systolic blood pressure (SBP) >140 and/or diastolic blood pressure (DBP) >90 mm Hg). We evaluated, at baseline and after 2, 4, 8, 12 and 16 weeks, clinic blood pressure, Ang II and PAI-1 antigen. Both imidapril and candesartan induced a similar SBP/DBP reduction (-19.4/16.8 and -19.5/16.3 mm Hg, respectively, P<0.001 vs. baseline). Both drugs decreased PAI-1 antigen after 4 weeks of treatment, but only the PAI-1 lowering effect of imidapril was sustained throughout the 16 weeks (-9.3 ng ml(-1), P<0.01 vs. baseline), whereas candesartan increased PAI-1 (+6.5 ng ml(-1), P<0.05 vs. baseline and P<0.01 vs. imidapril). Imidapril significantly decreased Ang II levels (-14.6 pg ml(-1) at week 16, P<0.05 vs. baseline), whereas candesartan increased them (+24.2 pg ml(-1), P<0.01 vs. baseline and vs. imidapril). In both groups there was a positive correlation between Ang II and PAI-1 changes (r=0.61, P<0.001 at week 16 for imidapril, and r=0.37, P<0.005 at week 16 for candesartan). Imidapril reduced plasma PAI-1 and Ang II levels, whereas candesartan increased them. This suggests that the different effect of angiotensin-converting enzyme inhibitors and Ang II blockers on Ang II production has a role in their different influence on fibrinolysis.

HEALTH CARE COSTS OF LOSARTAN AND CANDESARTAN IN THE PRIMARY TREATMENT OF HYPERTENSION: 6C.07

A recentstudy of two widely used angiotensin receptor blockers (ARBs) reported a reduced risk of cardiovascular events (−14.4%) when treating patients with candesartan compared to losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalisations, and laboratory tests) associated with losartan and candesartan treatment was estimated in 14,100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalisation. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%), and hospitalisations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years the mean total costs per patient were 10,435 Swedish kronor (SEK) (95% CI 3,086 to 17,783) higher in the losartan group. Prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan.

Health-care costs of losartan and candesartan in the primary treatment of hypertension

A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (−14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory tests) associated with losartan and candesartan treatment was estimated in 14 100 patients in a real-life clinical setting. We electronically extracted patient data from primary care records and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10 369 Swedish kronor (95% confidence interval: 3109–17 629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan.

The Additive Beneficial Effects of Ramipril Combined with Candesartan in Hypertensive Patients on Insulin Resistance, Plasma Adiponectin

Background and Objectives：Ramipril and candesartan have decreased the incidence of new onset diabetes in large scale randomized clinical studies. Because ramipril and candesartan have distinct mechanisms of action in the renin angiotensin aldosterone system, we hypothesized that combination therapy would have additive beneficial metabolic effects in patients with hypertension. Subjects and Methods：Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each being 2 months). Results：Ramipril, combination therapy or candesartan significantly increased the plasma adiponectin levels relative to the baseline measurements by 17±6% (p=0.038), 25±5% (p<0.001), and 14±6% (p=0.016), respectively. Combination therapy significantly increased the plasma adiponectin levels more than either ramipril or candesartan alone (p=0.020 by ANOVA). Only combination therapy significantly increased the QUICKI level relative to the baseline measurements (p=0.002). There were no significant correlations between these changes of the metabolic parameters and reduction of the systolic blood pressure (-0.288≤r≤ 0.284) and reduction of the diastolic blood pressure (-0.282≤r≤0.190). On multivariate analysis, only the change of adiponectin levels was an independent predictor of the changes in the QUICKI levels (β=1.549, p=0.040) following combination therapy. Conclusion：Ramipril in combination with candesartan increases the plasma adiponectin levels to a greater extent than monotherapy with either drug alone. Only combination therapy significantly improves insulin sensitivity relative to the baseline measurements. The only predictor for the improvement of insulin sensitivity is the increase of plasma adiponectin levels by combination therapy. (Korean Circulation J 2007;37:173-179)

Additive beneficial cardiovascular and metabolic effects of combination therapy with ramipril and candesartan in hypertensive patients

Ramipril and candesartan have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that combination therapy has additive beneficial effects to simultaneously improve endothelial dysfunction and adipocytokine profiles in patients with hypertension. Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each 2 months). Ramipril, candesartan, or combination therapy reduced blood pressure, improved flow-mediated dilation, and increased plasma adiponectin levels when compared with baseline values. However, combination therapy improved these outcome measures to a greater extent than either ramipril or candesartan alone (P < 0.001 and P = 0.016 for systolic and diastolic blood pressure, P < 0.001 and P = 0.048 for flow-mediated dilation and adiponectin levels by ANOVA). In addition, combination therapy reduced plasma leptin levels to a greater extent than either ramipril or candesartan alone (P = 0.042 by ANOVA). There were correlations between percent changes in adiponectin levels and percent changes in insulin sensitivity (determined by QUICKI) (r = 0.319, P = 0.066) following ramipril therapy, percent changes in QUICKI (r = 0.374, P = 0.029) following combination therapy, and percent changes in QUICKI (r = 0.607, P < 0.001) following candesartan therapy. Ramipril in combination with candesartan improves blood pressure, endothelial function, and adipocytokine profiles to a greater extent than monotherapy with either drug in hypertensive patients.

Anti-inflammatory and metabolic effects of candesartan in hypertensive patients

Background Angiotensin II type 1 (AT1) receptor blocker therapy prevented or retarded the progression of coronary heart disease. The mechanisms of this benefit may relate to the ability of AT1 receptor blockers to reduce inflammation and insulin resistance. Methods We administered placebo or candesartan 16 mg daily during 2 months to 45 patients with mild to moderate hypertension. This study was randomized, double-blind, placebo-controlled, crossover in design. Results Candesartan therapy significantly lowered both systolic and diastolic blood pressure. Compared with placebo, candesartan therapy significantly lowered plasma hsCRP levels relative to baseline measurements from 1.10 to 0.70 mg/l ( P = 0.024) and soluble CD40 ligand levels by 30 ± 11% ( P < 0.001). There were significant inverse correlations between body mass index and baseline plasma adiponectin levels ( r = − 0.480, P = 0.009). There were significant correlations between baseline adiponectin levels and baseline insulin ( r = − 0.317, P = 0.034) or baseline Quantitative Insulin-Sensitivity Check Index (QUICKI), a surrogate index of insulin sensitivity ( r = 0.371, P = 0.012). Compared with placebo, candesartan therapy significantly lowered fasting insulin levels ( P = 0.011) and increased plasma levels of adiponectin by 15 ± 4% ( P = 0.012) and increased QUICKI by 8 ± 2% ( P = 0.007). There were significant correlations between percent changes in adiponectin levels and percent changes in insulin ( r = − 0.340, P = 0.022) or QUICKI ( r = 0.325, P = 0.029). Conclusions Candesartan therapy significantly reduced inflammation and increased adiponectin levels and improved insulin sensitivity in hypertensive patients.

Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients

ObjectivesWe investigated the vascular effects of candesartan in hypertensive patients. BackgroundThe renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The plausible mechanisms are that angiotensin II promotes superoxide anion generation, endothelial dysfunction, inflammation, and impaired fibrinolysis. The effects of candesartan on these conditions have not been clearly observed. MethodsWe administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension. This was a randomized, double-blind, placebo-controlled, crossover study in design. ResultsCandesartan did not significantly change lipoprotein levels. However, compared with placebo, candesartan significantly reduced plasma levels of malondialdehyde from 1.50 ± 0.07 to 1.29 ± 0.09 μM (p = 0.009); improved the percent flow-mediated dilator response to hyperemia from 5.17 ± 0.24 to 6.22 ± 0.26% (p < 0.001); and, furthermore, reduced plasma levels of monocyte chemoattractant protein (MCP-1) from 213 ± 8 to 190 ± 7 pg/ml (p = 0.003), tumor necrosis factor-alpha from 2.93 to 2.22 pg/ml (p = 0.026), and plasminogen activator inhibitor type 1 from 74 ± 4 to 53 ± 4 ng/ml (p < 0.001) but not C-reactive protein (CRP), matrix metalloproteinase protein, and fibrinogen. There were no significant correlations between these changes and reduction of systolic blood pressure (BP) (−0.247 ≤ r ≤ 0.195) and between these changes and reduction of diastolic BP (−0.262 ≤ r ≤ 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (−0.119 ≤ r ≤ 0.127). Furthermore, we observed no significant correlations between CRP and MCP-1 levels (r = −0.162). ConclusionsInhibition of the angiotensin II type 1 (AT1) receptor in hypertensive patients reverses endothelial dysfunction, measured as an improvement in flow-mediated dilation and fibrinolysis and reduction of oxidant stress and inflammatory cytokines, suggesting that AT1 receptor blocker therapy has antiatherogenic effects.

A randomized, double-blind, controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus

Background: When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered. Objective: The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period. Methods: Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed. Results: Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m 2 in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m 2 in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG ( P < 0.05), FPI ( P < 0.05), TC ( P < 0.05), LDL-C ( P < 0.05), Lp(a) ( P < 0.05), PAM ( P < 0.05), and AER ( P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER ( P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group ( P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05). Conclusions: Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population.

Comparison between perindopril and candesartan in hypertensive patients with type 2 diabetes: evaluation of lipid profile and Lp (a)

Comparison between perindopril and candesartan in hypertensive patients with type 2 diabetes: evaluation of lipid profile and Lp (a)