Angiotensin Receptor Blocker Combination Therapy Research Articles

Arterial hypertension in children with nephrotic syndrome

The review presents materials on the prevalence of NS in children, variants of its course: steroid-sensitive (SSNS) and steroidresistant (SRNS) steroid-dependent (SSNS). Minimal change nephrotic syndrome minimal changes (NSMC) is the most common glomerular disorder. Although NSMC has an excellent prognosis with a low risk of progression to t-CRF, its recurrent nature requires children to receive frequent courses of steroid therapy and other medications, many of which are known to affect blood pressure (BP). The interrelation of NS in children with arterial hypertension (AH) is shown. Prevalence of hypertension in children with SCNS, SRNS, SZNS is given. The regulation of hypertension in children is mandatory in the treatment of NS, due to the fact that hypertension is not established in a timely manner, is insufficiently controlled and is often masked. Vascular dysregulation, fluid overload, increased cardiac output and peripheral vascular resistance, alone or in combination, can lead to hypertension in CKD. The use of modern methods to monitor and control blood pressure is critical for improving hypertension management and preventing target organ damage in children. 24-hour blood pressure measurements are an important tool in determining the prognosis and treatment of children with HC. Many comorbidities increase the risk of cardiovascular disease, including obesity, left ventricular hypertrophy (LVH), increased arterial stiffness (increased BMI, endothelial dysfunction), impaired glucose metabolism, and hyperlipidemia. The pathophysiological aspects of hypertension in children with NS are considered. The pathophysiology of hypertension in NS is complex, with many renal and extrarenal factors. Renal factors include sodium retention, fibrosis / decreased GFR, and progression of kidney disease, and a direct link between albuminuria and blood pressure has recently been described. Other factors include drug side effects, comorbidities and genetic predisposition. Sodium metabolism plays an important role in the development of edema and blood pressure regulation in NS. There are two main hypotheses for sodium retention in NS, the hypothesis of underfilling and overfilling. The role of the epithelial sodium channel (ENC), atrial natriuretic peptide (ANP), nitric oxide (NO), steroid hormones and other drugs in sodium retention and the pathogenesis of hypertension is also considered. In children with NS, hypertension leads to target organs damage (TOD): left ventricular hypertrophy (LVH), damage to the organ of vision, cognitive impairment and more rapid progression of chronic kidney disease. Salt restriction and RAAS inhibition are considered integral parts of the treatment of children with proteinuria, and both are known to have blood pressure lowering effects. The RAAS blockade has a renoprotective effect in patients with glomerular damage. Studies have found greater reductions in proteinuria with ACE / ARB combination therapy. This renoprotective effect is explained by both a decrease in blood pressure and mechanisms independent of blood pressure. Lifestyle modifications, weight control, healthy eating, reduced sodium intake, supportive exercise, and basic drug therapy using angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics can slow the progression of NS in children.

Safety and efficacy of empagliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post hoc analysis of data from the SACRA study.

Elderly diabetic patients are likely to have uncontrolled nocturnal hypertension, which confers higher risks of cardiovascular events and heart failure. To investigate the efficacy and safety of empagliflozin in elderly patients with type 2 diabetes (T2DM), a sub‐analysis was performed of data from the SGLT2 inhibitor and Angiotensin receptor blocker Combination theRapy in pAtients with diabetes and uncontrolled nocturnal hypertension (SACRA) study, a multi‐center, double‐blind, randomized, parallel study of T2DM patients who were treated with empagliflozin for 12 weeks. In the present analysis, we compared efficacy and safety outcomes in participants aged <75 and ≥75 years. At baseline, 44 participants were ≥75 years and 87 were <75 years. Nighttime ambulatory systolic blood pressure (SBP) decreased by 4.2 mm Hg in the ≥75‐year‐old group and by 7.9 mm Hg in the <75‐year‐old group (p = .884 for the between‐age group difference in the change between baseline and week 12) [primary endpoint]. Empagliflozin, but not placebo, significantly reduced mean 24‐h SBP (−8.7 mm Hg in ≥75‐year‐olds vs. −11.0 mm Hg in <75‐year‐olds) and daytime SBP (−10.8 mm Hg in ≥ 75‐year‐olds vs. −12.3 mm Hg in <75‐year‐olds) between baseline and week 12, with no significant differences between the groups. In addition, there were significant reductions in glycated hemoglobin, body weight, and uric acid during 12 weeks of empagliflozin treatment in the two age groups. The incidences of hypoglycemic episodes, hypotension, and metabolic adverse events were similar in the two groups. Thus, empagliflozin was effective and well tolerated in elderly diabetic patients with uncontrolled nocturnal hypertension when administered for 12 weeks.

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses.

DISTINCT was an 8‐week, double‐blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose‐response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment‐related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.

A systematic review and meta-analysis of aliskiren and angiotension receptor blockers in the management of essential hypertension

Aliskiren is a novel antihypertensive agent and the first direct renin inhibitor (DRI) in clinical use. Several clinical trials have compared DRI with angiotensin receptor blockers (ARBs) in the management of essential hypertension. However, systematic comparison of efficacy and safety between DRIs and ARBs is still lacking. We reviewed randomized controlled trials (RCTs) comparing aliskiren with ARBs for net reduction of blood pressure from baseline, achieved rate of control, and incidences of common and serious adverse events. Weighted mean differences (WMD) and relative risk (RR) with 95% confidence intervals (CI) were calculated for continuous and dichotomous data, respectively. Seven RCTs with 5488 patients were included in this meta-analysis. We compared the efficacy of aliskiren and ARBs in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP). No differences were found between the two groups. Aliskiren combined with ARBs was superior to aliskiren monotherapy at the maximum recommended dose on SBP and DBP reduction. (WMD -4.80, 95% CI -6.22-- -3.39, p < 0.0001; WMD -2.96, 95% CI -4.63-- -1.28, p = 0.0001; respectively). Similar results were found with aliskiren combined with ARBs versus ARB monotherapy (WMD -4.43, 95% CI -5.91-- -2.96, p < 0.0001; WMD -2.40; 95% CI -3.41-- -1.39, p < 0.0001; respectively). No differences were found in adverse events between the aliskiren and ARB groups. Similar results were found with aliskiren and ARB combination therapy and its respective monotherapy. We conclude that aliskiren's BP-lowering capabilities were comparable to those of ARBs. Aliskiren and ARB combination therapy provided more effective BP reduction than each respective monotherapy without increasing adverse events.

Angiotensin Receptor Blockers: Role in Hypertension Management, Cardiovascular Risk Reduction, and Nephropathy

The renin-angiotensin system (RAS) plays a central pathogenic role in the development of hypertension and associated vascular disorders. However, whether the two main classes of agents that blunt RAS activity-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-yield comparable cardioprotective and renoprotective effects in high-risk patients is controversial. An analysis of several controlled clinical trials provides evidence that, in patients with or without heart failure, ARBs provide protective effects and improvements in prognosis compared with those achieved with ACEIs. This article describes the critical studies that examine the cardioprotective and renoprotective efficacy of ARBs and identifies the populations and doses at which these agents are most effective. In the clinical setting, ARBs may be a valuable alternative to ACEI therapy. Because of their tolerability profile, ARBs or ARB combination therapy may be an option for patients susceptible to ACEI-related adverse events.

Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker

Podocyte injury and its subsequent loss in urine play an important role in the pathogenesis of diabetic nephropathy; blockade of the renin-angiotensin system may ameliorate the damage. In a non-randomized setting, we studied 71 patients with diabetic nephropathy on a stable dose of angiotensin-converting enzyme inhibitor (ACEI). In 37 patients, angiotensin receptor blocker (ARB) was added (the combination group); ACEI alone was continued in the other 34 (the control group). The mRNA expressions of nephrin, podocin, and synaptopodin in urinary sediment were measured at 0 and 12 weeks. Baseline glomerular filtration rate (GFR) correlated with the urinary expression of nephrin (r=0.320, P=0.007), podocin (r=0.336, P=0.004), and synaptopodin (r=0.350, P=0.003). After adjusting for the baseline expression, the combination group had a significantly lower urinary synaptopodin expression (7.49 (95% confidence interval CI, 0.62-115.29) vs 14.83 (95% CI, 1.03-241.43), P=0.026) than the control group after 12 weeks of treatment. The percentage change in urinary podocin expression over 12 weeks of treatment had a modest correlation with the rate of GFR decline in 1 year (r=-0.243, P=0.041). In patients with diabetic nephropathy, urinary mRNA expression of podocyte markers correlated with baseline renal function. Urinary expression of synaptopodin was lower after 12 weeks of ACEI and ARB combination therapy. Our result suggests that serial measurement of urinary podocyte markers may have a value for the monitoring of therapeutic response.