Doses Of Angiotensin II Receptor Blocker Research Articles

Neuroprotective effect of angiotensin II receptor blockers on the risk of incident Alzheimer's disease: A nationwide population-based cohort study.

Recent studies on renin-angiotensin system (RAS) inhibitors have reported a reduced risk of Alzheimer's disease (AD). Nevertheless, the effect of RAS inhibitor type and blood-brain barrier (BBB) permeability on the risk of AD is still unknown. To assess the effects of RAS inhibitors on the risk of AD based on the type and BBB permeability and investigate the cumulative duration-response relationship. This was a population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database records from 2008 to 2019. The data of patients diagnosed with ischemic heart disease between January 2009 and June 2009 were identified for inclusion in the analyses. Propensity score matching was used to balance RAS inhibitor users with non-users. The association between the use of RAS inhibitors and incident AD was evaluated using a multivariate Cox proportional hazard regression model. The results are presented in adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Among the 57,420 matched individuals, 7,303 developed AD within the follow-up period. While the use of angiotensin-converting enzyme inhibitors (ACEIs) was not significantly associated with AD risk, the use of angiotensin II receptor blockers (ARBs) showed a significant association with reduced risk of incident AD (aHR = 0.94; 95% CI = 0.90-0.99). Furthermore, the use of BBB-crossing ARBs was associated with a lower risk of AD (aHR = 0.83; 95% CI = 0.78-0.88) with a cumulative duration-response relationship. A higher cumulative dose or duration of BBB-crossing ARBs was associated with a gradual decrease in AD risk (P for trend < 0.001). No significant association between the use of ACEIs and the risk of AD was observed regardless of BBB permeability. Long-term use of BBB-crossing ARBs significantly reduced the risk of AD development. The finding may provide valuable insight into disease-modifying drug options for preventing AD in patients with cardiovascular diseases.

A PRACTICAL APPROACH TO SWITCH FROM A MULTIPLE PILL THERAPEUTIC STRATEGY TO A POLYPILL-BASED STRATEGY FOR SECONDARY PREVENTION IN PATIENTS WITH HYPERTENSION

Objective: The recommendation in hypertension is to initiate treatment with a combination of two blood pressure-lowering drugs in a single pill regardless of the cardiovascular (CV) risk, to add a statin in patients with established CV disease (CVD) or at moderate or high risk, and to add as well an antiplatelet agent only among those with established CVD. Some clinical guidelines nowadays endorse the polypill approach to increase the efficiency of the pharmacological treatment and decrease CV morbidity and mortality. The CNIC polypill is the only CV polypill marketed in Europe and the only approved by the EMEA for the secondary prevention of CVD. This polypill contains aspirin, ramipril, and atorvastatin. We aimed at helping clinicians to start treatment with the CNIC polypill switching from any other statin to atorvastatin, and from any angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) to ramipril. Design and method: We looked for available data and recommendations to build tables of equivalent effective daily doses of two of the polypill components (ramipril and atorvastatin), and we developed a treatment algorithm based on expert opinion. Results: We provide the approximate equivalent effective daily doses of other ACEIs and ARBs with ramipril and of other statins according to atorvastatin's potency. Moreover, to guide clinicians in the management of patients for secondary prevention of CVD, we provide a treatment algorithm and detail the indications and different available preparations to start treatment with the CV polypill in patients with high BP and prior CVD, and how to associate other BP-lowering drugs or lipid-lowering drugs if need be. Finally, we give advice on how to switch and adapt the treatment of patients already on fixed-dose combinations of antihypertensive medications to initiate the CV polypill regimen. Conclusions: The multiple doses of the individual components of the CNIC polypill versions allow for increased flexibility in prescribing and use it to start treatment in patients with high BP and prior CVD, and probably also in the particular scenario of hypertensive patients at high CVD risk without previous CV event and no significant risk of major bleeding.

Adverse impact of renin\u2013angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. This retrospective cohort study was performed in all hospitalized patients with COVID-19 in tertiary hospitals in Daegu, Korea. Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. The analysis of the primary outcome, in-hospital mortality, was performed using the Cox proportional hazards regression model. Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10–4.38; P = 0.025). ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02–6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15–8.15; P = 0.026). Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P < 0.05). ACE-I or ARB therapy in patients with severe COVID-19 was associated with the occurrence of severe complications and increased in-hospital mortality. The potentially harmful effect of ACE-I or ARB therapy may be higher in patients who received high doses.

Hemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin with renin-angiotensin system inhibitors in type 2 diabetic patients with albuminuria.

Objective:Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial.Methods:In this study, 360 individuals with type 2 diabetes and albuminuria receiving unchanged doses of ACE inhibitors or ARBs were randomized to linagliptin or placebo. Twenty-four-hour ambulatory BP monitoring, an exploratory endpoint, was conducted at baseline and after 24 weeks.Results:Ambulatory BP monitoring data were available for 208 individuals (linagliptin: n = 111; placebo: n = 97). Baseline mean ± SD 24-h SBP and DBP were 132.5 ± 12.4 mmHg and 75.9 ± 9.4 mmHg, respectively; mean 24-h HR was 76.3 ± 10.1 bpm. At week 24, no overall effect of the DPP-4 inhibitor versus placebo was seen on mean 24-h SBP, DBP, or HR. Furthermore, in the subgroups receiving either an ACE inhibitor or an ARB, no effect on these hemodynamic parameters was seen as a result of concomitant DPP-4 inhibitor treatment.Conclusion:Adding linagliptin to treatment with ACE inhibitors or ARBs was not associated with any hemodynamic changes, supporting their concomitant use in individuals with type 2 diabetes and albuminuria.

Doses of renin-angiotensin system inhibitors but not beta-blockers predict outcome after ST-elevation myocardial infarction

ABSTRACTObjectives: In patients with ST-elevation myocardial infarction (STEMI), it is not clear whether low-dose renin-angiotensin system inhibitors and beta-blockers can result in the same benefits achievable with higher target doses. This observational study aims to investigate whether higher doses of angiotensin converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) and beta-blockers can improve outcomes in patients with STEMI.Methods: We recorded daily doses of ACEI, ARB, and beta-blockers in 331 patients with STEMI. Echocardiographic studies were performed at baseline and were repeated 6 months later. Clinical events, including all-cause death and heart failure, were followed for 2 years.Results: Patients receiving high-dose ACEI/ARB had less increase in left ventricular end-diastolic volume index (LVEDVI) at 6 months. In multivariable linear regression model, ACEI/ARB dose or beta-blocker dose was not an independent predictor of increase in LVEDVI at 6 months. Kaplan-Meier survival curves showed that doses of ACEI/ARB (p = 0.003) and beta-blockers (p = 0.027) were significant predictors of death and heart failure. In multivariable Cox regression analysis, independent predictors of all-cause death and heart failure were diabetes mellitus (p = 0.001), left ventricular ejection fraction (p = 0.026), and ACEI/ARB dose (p = 0.025). Beta-blockers dose was not a predictor of clinical events in multivariable analysis (p = 0.413).Conclusion: High-dose ACEI/ARB, but not beta-blocker, was associated with lower rate of all-cause death and heart failure in patients with STEMI.

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study.

Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45-84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than -950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.

Analysis of second- and third-line antihypertensive treatments after initial therapy with an angiotensin II receptor blocker using real-world Japanese data.

Combination therapy using two or three classes of drugs is often required to treat hypertension to prevent cardiovascular disease. In this study, we examined combination therapies administered following initial therapy with an angiotensin II receptor blocker (ARB) in hypertensive Japanese patients. To determine which classes of antihypertensives are being prescribed as second- or third-line treatments for patients who were initially treated with a single ARB, we analyzed prescription claims data from two Japanese health-care databases for 2008 to 2015. Among the 26 998 patients who were initially treated with a single ARB (from one database), calcium channel blockers (CCBs) were the most frequently prescribed second-line antihypertensive, as these medicines were added for >20% of patients within 1 year of ARB prescription initiation. The addition rates of CCBs as a second-line therapy differed depending on the initial ARB type. In contrast, <10% of patients received a diuretic as a second-line antihypertensive. Among the 48 813 patients who were prescribed an ARB in combination with a CCB (as shown in the other database), diuretics were prescribed as third-line antihypertensives more frequently than increased doses of CCBs or ARBs. Diuretics were added for 8% of patients within 2 years of CCB addition, and the addition rates differed based on the CCB dose used for combination therapy. We also found that the addition rates of diuretics differed depending on patient clinical histories among ARB and CCB recipients.

Pharmacotherapy Treatment Patterns, Outcomes, and Health Resource Utilization Among Patients with Heart Failure with Reduced Ejection Fraction at a U.S. Academic Medical Center.

To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting. Retrospective analysis. Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower. The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received β-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of β-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a β-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (β-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673-0.857; multivariate: OR 0.768, 95% CI 0.625-0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4-3.1; multivariate: OR 2.1, 95% CI 1.3-3.5). During a mean ± SD follow-up of 36 ± 27 months, all-cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure-specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 ± 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases. This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities.

Differential effects of angiotensin II receptor blocker and losartan/hydrochlorothiazide combination on central blood pressure and augmentation index

Central systolic blood pressure (CSBP) may be a better predictor of cardiovascular risk than clinic brachial (B)SBP. The effects of dose increment from medium dose of angiotensin II receptor blockers (ARBs) to the maximum dose of ARBs (maximum) and changing from medium dose of ARBs to losartan 50 mg/hydrochlorothiazide 12.5 mg combination (combination) were compared in hypertensive patients in whom monotherapy with a medium ARB dose did not achieve goal home SBP (135 mmHg). Four weeks after treatment with a medium ARB dose monotherapy, those whose home SBP level was above 135 mmHg were randomized to receive the maximum ARB dose (n = 101) or the combination (n = 99) once daily for 8 weeks. Both regimens significantly decreased BSBP and CSBP, while a decrease in BSBP and CSBP was greater with combination. The maximum significantly decreased augmentation index (AIx), while the combination did not. The rate of a decrease in reflection to decrease in CSBP was greater in the maximum than in the combination. In the elderly subgroup, the combination more effectively lowered BSBP than the maximum, and only the combination decreased CSBP. However, in the young subgroup, the maximum decreased AIx more than combination, while both regimens lowered CSBP and BSBP to a similar extent. It is explained in part that the maximum may affect pulse wave reflection more predominantly than the combination, especially in young subjects. A weak effect on pulse wave reflection and, thus, on CSBP, of the combination may be overcome by the potent antihypertensive effect of this regimen.

Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation

Higher doses of AngII (angiotensin II) blockers are intended to optimize albuminuria reduction rather than for blood pressure control in chronic kidney disease. However, the long-term renoprotection of high-dose AngII blockers has yet to be defined. The present study sought to determine whether doses of ARB (AngII receptor blocker) that maximally reduce proteinuria could slow the progression of glomerulosclerosis in the uninephrectomized db/db mouse, a model of Type2 diabetes. Untreated uninephrectomized db/db mice had normal blood pressure, but developed progressive albuminuria and mesangial matrix expansion between 18 and 22weeks of age, which was associated with increased renal expression of TGFβ1 (transforming growth factor β1), PAI-1 (plasminogen-activator inhibitor-1), typeIV collagen and FN (fibronectin). Treatment with valsartan in the drinking water of db/db mice from 18 to 22weeks of age, at a dose that was determined previously to maximally reduce proteinuria, prevented the increases in albuminuria and the markers of renal fibrosis seen in untreated db/db mice. In addition, WT-1 (Wilms tumour protein-1)-immunopositive podocyte numbers were found to be lower in the untreated glomeruli of mice with diabetes. The expression of podocin and nephrin were continually decreased in mice with diabetes between 18 and 22weeks of age. These changes are indicative of podocyte injury and the administration of valsartan ameliorated them substantially. Renal expression of TNFα (tumour necrosis factor α), MCP-1 (monocyte chemoattractant protein-1), Nox2 (NADPH oxidase 2), p22phox and p47phox and urine TBARS (thiobarbituric acid-reacting substance) levels, the markers of renal inflammation and oxidative stress, were increased during disease progression in mice with diabetes. Valsartan treatment was shown to reduce these markers. Thus high doses of valsartan not only reduce albuminuria maximally, but also halt the progression of the glomerulosclerosis resulting from Type2 diabetes via a reduction in podocyte injury and renal oxidative stress and inflammation.

Regression of Electrocardiographic Signs of Left Ventricular Hypertrophy by Combined Treatment With Thiazide Diuretic and Angiotensin-II Receptor Blocker.

In hypertensive patients, left ventricular hypertrophy (LVH) may persist despite satisfactory blood pressure (BP) control. The efficacy of thiazide diuretics in Western countries has been reported, but whether this applies to hypertensive Japanese patients is uncertain. METHODS AND RESULTS: We randomly assigned 94 patients whose BP was poorly controlled with usual doses of angiotensin-II receptor blockers (ARB), to losartan/hydrochlorothiazide (HCTZ) fixed-dose combination vs. maximum doses of ARB. After 6 months follow-up, decrease in BP, regression of electrocardiographic LVH, and changes in laboratory measurements were examined. Although a similar decrease in BP was observed in both groups, the decrease in LV Sokolow-Lyon voltage, from 34.4±9.2 to 29.4±8.8 mm in the losartan/HCTZ vs. from 29.9±10.2 to 29.1±8.4 mm in the ARB group (P=0.0003), and the decrease in serum B-type natriuretic peptide (BNP) level, from 30.1±28.5 to 26.8±28.0 pg/ml vs. from 23.7±14.8 to 29.8±29.3 pg/ml (P=0.045) were greater in the losartan/HCTZ group. By single variable logistic regression analysis, ∆BNP (P=0.012) and treatment with losartan/HCTZ (P<0.0001) correlated with the regression of LVH. By multiple variable logistic regression analysis, both ∆BNP (P=0.035) and treatment with losartan/HCTZ (P=0.0003) remained significant. No major adverse effects were observed. Greater regression of LVH was safely achieved with losartan/HCTZ in patients whose BP was poorly controlled with an ARB.

Combination of sorafenib and angiotensin-II receptor blocker attenuates preneoplastic lesion development in a non-diabetic rat model of steatohepatitis

Given the well-documented adverse side effects of sorafenib, many sorafenib-treated patients may need the reduced initial dose of the compound, and an alternative sorafenib-based therapy, which exerts similar clinical benefit, is anticipated. An angiostatic therapy with sorafenib is considered one of the promising approaches for chemoprevention of hepatocellular carcinoma. The aim of the current study was to elucidate the combination effect of low dose of sorafenib and angiotensin-II receptor blocker (ARB) on hepatocarcinogenesis, especially in conjunction with angiogenesis. The chemopreventive effect on the development of liver preneoplastic lesions, angiogenesis, and several indices was elucidated in rats. We also performed several sets of in vitro experiments to examine the mechanisms involved. Using a non-diabetic rat model of steatohepatitis with choline deficient L-amino acid-defined diet, sorafenib demonstrated marked inhibition of preneoplastic lesions in a dose dependent manner. Combined treatment with ARB (losartan) at a clinically comparable dose and half dose of sorafenib resulted in the inhibitory effect equivalent to that of common dose of sorafenib along with suppression of hepatic neovascularization and potent angiogenic factor, vascular endothelial growth factor. Furthermore, similar combined inhibitory outcomes were observed in several sets of in vitro studies. Since the combinatorial treatment using low doses of sorafenib and ARB could sufficiently induce inhibitory effect on the development of preneoplastic lesions at the magnitude similar to the conventional dose of sorafenib, this regimen may provide new strategy for patients intolerant of the usual dose of sorafenib in the future.

T/L-type calcium channel blocker reduces the composite ranking of relative risk according to new KDIGO guidelines in patients with chronic kidney disease.

BackgroundRecently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with chronic kidney disease (CKD) be assigned according to stage and composite relative risk on the basis of glomerular filtration rate (GFR) and albuminuria criteria. The aim of this post-hoc analysis was to investigate the effects of add-on therapy with calcium channel blockers (CCBs) on changes in the composite ranking of relative risk according to KDIGO guidelines. Benidipine, an L- and T-type CCB, and amlodipine, an L-type CCB to angiotensin II receptor blocker (ARB), were examined.MethodsPatients with blood pressure (BP) > 130/80 mmHg, an estimated GFR (eGFR) of 30–90 mL/min/1.73 m2, and albuminuria > 30 mg/gCr, despite treatment with the maximum recommended dose of ARB, were randomly assigned to two groups. Each group received one of two treatments: 2 mg benidipine daily, increased to 8 mg daily (n = 52), or 2.5 mg amlodipine daily, increased to 10 mg daily (n = 52).ResultsAfter 6 months of treatment, a significant and comparable reduction in systolic and diastolic BP was observed in both groups. The eGFR was significantly decreased in the amlodipine group, but there was no significant change in the benidipine group. The decrease in albuminuria in the benidipine group was significantly lower than in the amlodipine group. The composite ranking of relative risk according to the new KDIGO guidelines was significantly improved in the benidipine group; however, no significant change was noted in the amlodipine group. Moreover, significantly fewer cases in the benidipine group than the amlodipine group showed a reduced risk category score.ConclusionThe present post-hoc analysis showed that compared to amlodipine benidipine results in a greater reduction in albuminuria accompanied by an improved composite ranking of relative risk according to the KDIGO CKD severity classification.Trial registrationTrial registration Number: UMIN000002644

Diuretics enhance effects of increased dose of candesartan on ambulatory blood pressure reduction in Japanese patients with uncontrolled hypertension treated with medium-dose angiotensin II receptor blockers

Although blockade of the renin–angiotensin system by increasing the dose of angiotensin II receptor blockers (ARBs) is recommended to achieve clinical benefits in terms of blood pressure (BP) control and cardiovascular and renal outcomes, the effect of this increased dose on ambulatory BP monitoring has not been evaluated completely in Japanese patients with uncontrolled hypertension undergoing medium-dose ARB therapy. The primary objective of this study was to examine the effect of the relatively high dose of the ARB candesartan (12 mg/day) on 24-h systolic BP and the attainment of target BP levels in uncontrolled hypertension treated with a medium dose of ARBs. A total of 146 hypertensive patients (age: 69.9 ± 9.3 years; females: 65.8%) completed the study. After switching to candesartan at 12 mg/day, all these BP measurements decreased significantly (p < 0.001). Attainment of the target office BP (p = 0.0014) and 24-h BP levels (p = 0.0296) also improved significantly. Subgroup analysis indicated that the reduction of 24-h systolic BP was larger in patients treated with diuretics than those without (p = 0.0206). Multivariate analysis revealed a significant correlation between the combined ARB and diuretic therapy, and the change in 24-h systolic BP irrespective of preceding ARBs. In conclusion, the switching therapy to increased dose of candesartan caused significant reductions in office and ambulatory BP levels, and improved the attainment of target BP levels in patients with uncontrolled hypertension treated with a medium dose of ARBs. Combination with diuretics enhanced this effect.

Losartan

Losartan

Pneumonia Risk and Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

BackgroundRecent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan.MethodsWe conducted a case-crossover study using the Taiwan Longitudinal Health Insurance Database for the year 2005. Data from patients hospitalized for the first time for pneumonia during 1997–2007 were analyzed. The case period was defined as the 30 days before admission; the periods 90 to 120 days and 180 to 210 days before admission were used as control periods. Prescribing status of ACE inhibitors and ARBs during the 3 periods was assessed for each patient. Conditional logistic regression was used to estimate the odds ratio (OR) for pneumonia associated with use of ACE inhibitors and ARBs.ResultsWe identified 10 990 cases of hospitalization for new pneumonia. After adjustment for time-variant confounding factors, pneumonia was not associated with use of ACEI or ARBS: the ORs were 0.99 (95% CI, 0.81–1.21) and 0.96 (0.72–1.28), respectively. No association was seen for cumulative defined daily doses (DDDs), as compared with nonusers, for 0 to 30, 31 to 60, or more than 60 DDDs. The results were found to be robust in sensitivity analysis.ConclusionsNeither the use nor cumulative dose of ACE inhibitors or ARBs was associated with pneumonia among the Taiwanese general population.

Comparison of medium-dose losartan/hydrochlorothiazide and maximal-dose angiotensin II receptor blockers in the treatment of Japanese patients with uncontrolled hypertension: the Kobe-CONNECT Study

The objective of this study is to examine the effects of thiazide diuretics, plus medium-dose losartan versus maximal-dose angiotensin II receptor blockers (ARBs) on blood pressure (BP) in Japanese patients with uncontrolled hypertension despite the use of medium-dose ARBs. Hypertensive patients in whom BP was inadequately controlled by treatment with medium-dose ARBs alone or with calcium-channel blockers were enrolled. Patients were randomly assigned to a fixed-dose combination of 50 mg per day losartan and 12.5 mg per day hydrochlorothiazide (HCTZ; n=98), or to a maximal dose of current ARBs (n=95). The reduction in office BP from baseline was significantly larger in the losartan/HCTZ group than in the maximal-dose ARB group (systolic BP -22.7±13.7 vs. -11.7±13.0 mm Hg, diastolic BP -9.6±10.9 vs. -4.5±11.0 mm Hg; P<0.01, respectively). The proportion of patients in whom the therapeutic target BP was achieved was greater in the losartan/HCTZ group than in the maximal-dose ARB group (59.2 vs. 26.3%; P<0.001). Both early-morning and evening BP were controlled more effectively over 1 year of treatment in the losartan/HCTZ group than in the maximal-dose ARB group (the mean BP difference between the groups, early-morning: 5.6 mm Hg (P=0.001), evening: 3.8 mm Hg (P=0.049)). Adverse changes in serum potassium and uric acid were observed in the losartan/HCTZ group; however, both changes were very slight, and the values were still within the normal range. The concomitant usage of losartan and HCTZ had no influence on glucose metabolism and lipid profiles. Declines in plasma N-terminal pro-brain natriuretic peptide levels and urinary albumin excretion were observed in the losartan/HCTZ group, but not in the maximal-dose ARB group. Switching from medium-dose ARBs to losartan plus HCTZ reduced both office and home BP efficiently in patients with uncontrolled hypertension.

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6 mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Additive renoprotective effects of aliskiren on angiotensin receptor blocker and calcium channel blocker treatments for type 2 diabetic patients with albuminuria

This open-label, randomized, parallel-controlled study investigated the effects of the direct renin inhibitor aliskiren on 64 hypertensive type 2 diabetic patients with chronic kidney disease (CKD) and stable glycemic control who were already being treated with fixed doses of antihypertensive agents over a 24-week period. These agents were 80 mg of the angiotensin II receptor blocker (ARB) telmisartan and 5 mg of the calcium channel blocker (CCB) amlodipine. Patients were randomly assigned to two groups: the aliskiren group, receiving 150 mg per day aliskiren, which was increased to 300 mg per day (n=32), and the CCB group, which received an increased dose (7.5 mg per day) of amlodipine that was increased to 10 mg per day (n=32). Urinary albumin excretion and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) were investigated in each group. Mean systolic and diastolic blood pressure decreased significantly in both groups, but there was no significant difference between the two groups at the end of the study. Serum creatinine levels and estimated glomerular filtration rate did not differ significantly between the two groups, but percent changes of urinary albumin/creatinine ratios, 8-OHdG and L-FABP levels decreased significantly in the aliskiren group compared with the CCB group. Plasma aldosterone levels were significantly decreased in the aliskiren group, which correlated significantly with those of urinary 8-OHdG and L-FABP. Our results suggest that the addition of aliskiren to the maximal recommended dose of ARB and usual dose of amlodipine is more effective in reducing albuminuria and oxidant stress in hypertensive diabetic patients with CKD than increasing the dose of amlodipine.

The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting

The 7th American Urological Association and the Japanese Urological Association International Affiliate Society Meeting