Conventional Antihypertensive Therapy Research Articles

Hipertensão refratária em paciente jovem: Um relato de caso

Introduction: Pheochromocytoma, a rare tumor originating from the chromaffin tissue of the adrenal medulla, has a prevalence of about 0.1-0.6% in patients with hypertension. Usually benign, its surgical removal can be curative. However, delays in diagnosis and inadequate treatment can lead to high mortality and morbidity rates. Case Report: A 23-year-old man with a history of resistant hypertension since December 2022 presented with symptoms of headache, palpitation, sweating, and anxiety. Tests revealed elevated levels of metanephrines and catecholamines, leading to the suspicion of pheochromocytoma. An MRI of the abdomen identified an expansive lesion in the right adrenal gland. Treatment included clinical management with alpha- and beta-blockers, followed by successful adrenalectomy, resulting in improvement of symptoms and hypertension. Discussion: The case illustrates the complexity inherent in the diagnosis of pheochromocytoma, a condition that often manifests surreptitiously in hypertensive patients. Resistance to conventional antihypertensive therapy, combined with symptoms such as headache, palpitations, and sweating, should raise suspicions of secondary hypertension and, consequently, pheochromocytoma. This case underlines the importance of a meticulous diagnostic evaluation in patients with refractory hypertension. Conclusion: Pheochromocytoma, despite being a rare cause of hypertension, represents a crucial differential diagnosis in secondary hypertension. Early diagnosis and appropriate surgical intervention are essential to prevent associated morbidity and mortality. This case reinforces the need for clinical surveillance for suggestive symptoms and the importance of appropriate diagnostic investigations in patients with resistant hypertension, particularly in young people.

Formulation and Characterization of Nanoparticulate Drug Carrier System for Lacidipine.

Lacidipine, a calcium channel antagonist, is primarily used to treat hypertension. It is classified as a Biopharmaceutics Classification System Class II drug and exhibits an oral bioavailability of 10% due to its extensive hepatic first-pass metabolism. This research study focused on formulating lacidipine-loaded cubosomal nanovesicles developed into rapidly dissolving oral films as an alternative to overcome the downsides faced by conventional antihypertensive therapy. Lacidipine-loaded cubosomes were prepared utilizing a top-down technique using lipid and surfactant and were further developed into fast dissolving oral films. Box-Behnken design was used for the optimization of process variables to achieve minimum particle size and greater entrapment efficiency of the nanovesicles, and response data were statistically evaluated. The optimized cubosomal dispersions upon characterization reported particle size within nanorange (116.8-341 nm) and an entrapment efficiency of 88.15%-97.1%, with 91.72% of total drug content. Morphological studies revealed uniformly dispersed vesicles with cubic to spherical shape. Oral rapidly dissolving films, after evaluation, were reported to have transparent to opaque appearance with a highly porous nature, which was confirmed by scanning electron microscopic imaging and displayed uniformity in weight and thickness and reported optimum mechanical strength and considerable flexibility, with disintegration time of 37.67 ± 3.68 s and exhibited 91.44% ± 1.65% in vitro drug release after 6 min. Short-term stability studies conducted on films at 25°C ± 2°C and 60% ± 5% relative humidity for 3 months demonstrated no significant variation in morphological and mechanical properties. Therefore, lacidipine-loaded cubosomal rapid dissolving oral films may be a promising formulation approach for the management of hypertension.

Effects of Carvedilol on Blood Pressure, Blood Sugar, and Blood Lipids in Elderly Patients with Refractory Hypertension.

Refractory hypertension seriously affects the life safety of patients. To investigate the effect of carvedilol combined with conventional antihypertensive therapy on blood pressure, blood sugar, blood lipids, and cardiovascular and cerebrovascular complications in elderly patients with refractory hypertension, a total of 80 elderly patients with refractory hypertension who were admitted from June 2019 to September 2021 were selected as the retrospective research objects and divided into the observation group and the control group according to the random number table method, 40 cases in each group, and the control group received conventional antihypertensive therapy. On this basis, the observation group was treated with carvedilol, and the effects of blood pressure, blood sugar, blood lipids, and cardiovascular and cerebrovascular complications were analyzed in the two groups. After treatment, the systolic blood pressure, diastolic blood pressure, adrenal medulla (AM), and endothelin (ET) of the observation group were significantly lower than those of the control group, but the heart rate and NO of the observation group were significantly higher than those of the control group. After treatment, the fasting blood glucose, insulin, triacylglycerol (TG), cholesterol (CHO), and low-density lipoprotein (LDL-C) of the observation group were significantly higher than those of the control group, but the ISI and HDL-C of the observation group were significantly lower than those of the control group. After treatment, the levels of IL-1β, IL-6, TNF-α, UAER, BUN, and SCr in the observation group were significantly lower than those in the control group. The TC of the observation group was lower than that of the control group. Combination therapy has a remarkably stable, sustained, and safe antihypertensive effect on patients with refractory hypertension.

Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels.

The antidiabetic drug empagliflozin is reported to produce a range of cardiovascular effects, including a reduction in systemic blood pressure. However, whether empagliflozin directly modulates the contractility of resistance-size mesenteric arteries remains unclear. Here, we sought to investigate if empagliflozin could relax resistance-size rat mesenteric arteries and the associated underlying molecular mechanisms. We found that acute empagliflozin application produces a concentration-dependent vasodilation in myogenic, depolarized and phenylephrine (PE)-preconstricted mesenteric arteries. Selective inhibition of smooth muscle cell voltage-gated K+ channels KV1.5 and KV7 abolished empagliflozin-induced vasodilation. In contrast, pharmacological inhibition of large-conductance Ca2+-activated K+ (BKCa) channels and ATP-sensitive (KATP) channels did not abolish vasodilation. Inhibition of the vasodilatory signaling axis involving endothelial nitric oxide (NO), smooth muscle cell soluble guanylyl cyclase (sGC) and protein kinase G (PKG) did not abolish empagliflozin-evoked vasodilation. Inhibition of the endothelium-derived vasodilatory molecule prostacyclin (PGI2) had no effect on the vasodilation. Consistently, empagliflozin-evoked vasodilation remained unaltered by endothelium denudation. Overall, our data suggest that empagliflozin stimulates smooth muscle cell KV channels KV1.5 and KV7, resulting in vasodilation in resistance-size mesenteric arteries. This study demonstrates for the first time a novel mechanism whereby empagliflozin regulates arterial contractility, resulting in vasodilation. Due to known antihypertensive properties, treatment with empagliflozin may complement conventional antihypertensive therapy.

A2026 Effect of Anxiolytic Therapy on Blood Pressure in Elderly Patients with Hypertension in Flood Disaster Area

Objectives: To investigate the changes of blood pressure fluctuation in elderly hypertensive patients in flood areas and the effects of anti-anxiety therapy on blood pressure related factors. Methods: The patients anesthesia group, which received conventional medical antihypertensive therapy while increasing the anxiolytic drugs and psychological counseling treatment; Control group were simply given conventional medical antihypertensive drugs. After 8 weeks of treatment, HAMA score, MBPS, BPV,PPI,AASI, CAP and PWV changes between the two groups. Results: 276 cases of elderly hypertensive patients have appeared the varying degrees of anxiety in the process of flooding and reconstruction, and blood pressure fluctuations along with it. After treatment for 8 weeks, the HAMA score, blood pressure variability (MBPS, short-term BPV) and PPI of the two groups were significantly improved (P < 0.05).And the improvement of HAMA score of the anxiolytic group was better than that of the control group (P < 0.05), as well as the blood pressure variability (MBPS, short-term BPV) and the improvement of PPI of the anxiolytic group were also better than those of the latter. However, the indexes of CAP, AASI and PWV in the two groups had no significant difference compared with those before treatment, the difference was not statistically significant (P > 0.05). Conclusion: Flooding and post-disaster reconstruction can easily cause different levels of anxiety in the elderly population, which may lead to the state of stress in elderly hypertensive patients. The elderly patients with hypertension who underwent flood and post-disaster reconstruction were treated with conventional antihypertensive therapy, as well as with anti-anxiety treatment and psychological counseling, which could effectively improve the clinical control of blood pressu

Arterial (Aortic) Stiffness in Patients with Resistant Hypertension: from Assessment to Treatment

The purpose of the review is to examine whether measurement of aortic stiffness could be especially value-adding for risk stratification and treatment among patients with resistant hypertension (RH). Adverse arterial remodeling and increased aortic stiffness is associated with RH, and it may be of additional clinical benefit to measure aortic stiffness in these patients. However, there is insufficient evidence to determine whether aortic stiffness is excessively high relative to the level of blood pressure (BP) among people with RH. This issue needs resolution as it could help refine management decisions guided by aortic stiffness. If conventional antihypertensive therapy fails to lower BP in patients with RH, there is good rationale for effectiveness of spironolactone as add on therapy, and this should also improve aortic stiffness. Lifestyle intervention with exercise and diet should be additionally efficacious towards improving BP and aortic stiffness in patients with RH, but there is limited data in this patient population. For better characterization on the effects of BP treatment on aortic stiffness, measures of central aortic BP may help refine management decisions above and beyond conventional arm cuff BP. There is strong evidence to support the use of aortic stiffness as a tool to aid risk stratification in hypertension management. Although there is a theoretical basis for special additional benefit of measuring aortic stiffness in patients with RH (as distinct from uncomplicated hypertension), at this time, there is inadequate data available to make definitive conclusions and is an area for future investigation.

21 Progressive vasculo-ventricular remodelling in persistent asymptomatic left ventricular diastolic dysfunction and links with immune-inflammatory biochemical markers

Background The natural history of persistent asymptomatic left ventricular diastolic dysfunction (ALVDD) is not fully understood. Altered immune-inflammatory markers have been linked to extracellular matrix remodelling of myocardial interstitium and perivasculature in hypertensive animal models. We aimed to evaluate the link between immune-inflammatory markers and vasculo-ventricular remodelling in ALVDD. Methods 91 asymptomatic hypertensive patients from the community were consecutively enrolled and subjected to guideline-based management at a dedicated Blood Pressure Unit. Demographics, Doppler-echocardiography and serum biomarkers were measured at baseline and routine 12 month follow-up. Patients with ALVDD (left atrial volume index (LAVi) > 34 ml/m 2 , n = 22) and Comparators (LAVi 2 , n = 44) were propensity matched to age in 1:2 ratio at baseline. From this cohort, patients with persistent ALVDD (at both timepoints, n = 10) were observed against others (n = 56). Results ALVDD was associated with higher serum natriuretic peptide, matrix metalloproteinase (MMP)-2, LAVi and left ventricular mass index versus Comparators at baseline. All patients had mean ejection fraction (EF) 67 ± 8%. Over the follow-up duration, persistent AVLDD was associated with greater increase in monocyte chemoattractant protein-1 (924.6 ± 2420.3 vs 198.5 ± 239.4 pg/ml) and aortic root diameter (0.27 ± 0.45 vs 0.06 ± 0.27 cm) with reduction in EF (-5.4 ± 5.2 vs -0.2 ± 7.0%) versus others; all p Conclusion Persistent ALVDD is associated with progressive vascular and ventricular remodelling not optimally negated by conventional anti-hypertensive therapies. These changes are linked to altered immune-inflammatory markers. The impact of inhibiting these markers requires further evaluation.

Renal denervation superior to drug therapy in hypertension

Despite widespread use of conventional antihypertensive therapy, which effectively reduces blood pressure in most hypertensive patients, a failure to attain target blood pressure levels in about 10% of patients with arterial hypertension suggests a deficit in present strategies, leaving this patient cohort at high risk of cardiovascular and renal disease.1 Although mechanisms underlying the pathogenesis of arterial hypertension are complex and multifactorial, augmented sympathetic activation crucially contributes to hypertension and its adverse effects.

Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats

We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30–40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy.

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Observations of Changes of Blood Pressure Before and after Neurosurgical Decompression in Hypertensive Patients with Different Types of Neurovascular Compression of Brain Stem

Aims: The neurovascular pulsatile compression of the rostral ventrolateral medulla can be divided into different subtypes. The posterior inferior cerebellar artery and/or vertebral artery can compress either the rostral ventrolateral medulla or the cranial nerves IX and X or both and on left, right or both sides. Methods: It was retrospectively investigated whether the types of neurovascular compression can influence blood pressure values. Data from 13 resistant hypertensive patients after decompression were investigated. Results: Six patients had 2 compressions, two had only medulla compression, four had only nerve compression on the left side and one had 2 compressions on both sides. There was no correlation between the types of compression and the levels of blood pressure, either before or after the decompression. Both, systolic and diastolic blood pressures and pulse pressure also decreased in all cases after the decompression but the change was significant only in the group with 2 compressions on the left side. Conclusion: According to our data, in a severe hypertension not responding to conventional antihypertensive therapy, the surgical decompression of the brain stem independently of the types of neurovascular compression could guarantee a decrease of blood pressure and improved sensitivity to antihypertensive medication.

Aged garlic extract reduces blood pressure in hypertensives: a dose–response trial

Background/objectives:Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose–response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension.Subjects/methods:A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose–response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire.Results:Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (−7.4±4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily.Conclusions:Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy.

Comparing marginal structural models to standard methods for estimating treatment effects of antihypertensive combination therapy

BackgroundDue to time-dependent confounding by blood pressure and differential loss to follow-up, it is difficult to estimate the effectiveness of aggressive versus conventional antihypertensive combination therapies in non-randomized comparisons.MethodsWe utilized data from 22,576 hypertensive coronary artery disease patients, prospectively enrolled in the INternational VErapamil-Trandolapril STudy (INVEST). Our post-hoc analyses did not consider the randomized treatment strategies, but instead defined exposure time-dependently as aggressive treatment (≥3 concomitantly used antihypertensive medications) versus conventional treatment (≤2 concomitantly used antihypertensive medications). Study outcome was defined as time to first serious cardiovascular event (non-fatal myocardial infarction, non-fatal stroke, or all-cause death). We compared hazard ratio (HR) estimates for aggressive vs. conventional treatment from a Marginal Structural Cox Model (MSCM) to estimates from a standard Cox model. Both models included exposure to antihypertensive treatment at each follow-up visit, demographics, and baseline cardiovascular risk factors, including blood pressure. The MSCM further adjusted for systolic blood pressure at each follow-up visit, through inverse probability of treatment weights.Results2,269 (10.1%) patients experienced a cardiovascular event over a total follow-up of 60,939 person-years. The HR for aggressive treatment estimated by the standard Cox model was 0.96 (95% confidence interval 0.87-1.07). The equivalent MSCM, which was able to account for changes in systolic blood pressure during follow-up, estimated a HR of 0.81 (95% CI 0.71-0.92).ConclusionsUsing a MSCM, aggressive treatment was associated with a lower risk for serious cardiovascular outcomes compared to conventional treatment. In contrast, a standard Cox model estimated similar risks for aggressive and conventional treatments.Trial registrationClinicaltrials.gov Identifier: NCT00133692

Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches

The conventional antihypertensive therapies including renin–angiotensin–aldosterone system antagonists (converting enzyme inhibitors, receptor blockers, renin inhibitors, and mineralocorticoid receptor blockers), diuretics, β-blockers, and calcium channel blockers are variably successful in achieving the challenging target blood pressure values in hypertensive patients. Difficult to treat hypertension is still a commonly observed problem world-wide. A number of drugs are considered to be used as novel therapies for hypertension. Renalase supplementation, vasopeptidase inhibitors, endothelin antagonists, and especially aldosterone antagonists (aldosterone synthase inhibitors and novel selective mineralocorticoid receptor blockers) are considered an option in resistant hypertension. In addition, the aldosterone antagonists as well as (pro)renin receptor blockers or AT2 receptor agonists might attenuate end-organ damage. This array of medications has now been complemented by a number of new approaches of non-pharmacological strategies including vaccination, genomic interference, controlled breathing, baroreflex activation, and probably most successfully renal denervation techniques. However, the progress on innovative therapies seems to be slow and the problem of resistant hypertension and proper blood pressure control appears to be still persisting. Therefore the regimens of currently available drugs are being fine-tuned, resulting in the establishment of several novel fixed-dose combinations including triple combinations with the aim to facilitate proper blood pressure control. It remains an exciting question which approach will confer the best blood pressure control and risk reduction in this tricky disease.

Clinical utility of valsartan in treatment of children and adolescents with high blood pressure

The incidence of hypertension in the pediatric population has been increasing secondary to lifestyle changes in children and adolescents. Recent studies have enhanced our understanding of the treatment of pediatric hypertension. Angiotensin-converting enzyme inhibitors have traditionally been the most commonly used class of medication in children with hypertension. This is partly due to the important role of the renin angiotensin aldosterone system pathway in the mediation of pediatric hypertension. Angiotensin receptor blockers provide a reasonable alternative to angiotensin-converting enzyme inhibitors. The need for better tolerated antihypertensives had led to development of many new antihypertensives. Valsartan is a relatively novel angiotensin receptor blocker that has been shown to be effective in the treatment of pediatric hypertension. Two recent trials have demonstrated the efficacy of valsartan monotherapy in the pediatric population aged 1–16 years. Once-daily oral preparations of valsartan achieve adequate blood pressure control in the pediatric population. Lack of generic formulations is an important disadvantage. Plasma levels are predictable and clearance is primarily by the liver. Valsartan should be prescribed cautiously for sexually active adolescent females due to concern about angiotensin receptor blocker fetopathy. Otherwise, the drug has infrequent side effects. In summary, valsartan is a new and useful alternative to conventional antihypertensive therapy in pediatric population.

Effects and mechanisms of angiotensin II receptor blockade with telmisartan in a normotensive model of mesangioproliferative nephritis

Renoprotective actions of angiotensin receptor blockers are not well established in normotensive, low-grade proteinuric glomerular diseases. We examined the effect of low-dose telmisartan (LT) and high-dose telmisartan (HT) versus conventional antihypertensive therapy in the rat anti-Thy1.1 model of glomerulonephritis. Rats were randomized on Day 4 after disease induction to no treatment (CT, control), LT or HT or hydrochlorothiazide + hydralazine (HCT + H). All rats remained normotensive: HT and HCT + H reduced blood pressure by 15-20%. LT, HT and HCT + H reduced glomerular endothelial cell proliferation and glomerular and interstitial matrix deposition on Day 14. Only HT reduced podocyte damage and tubular cell dedifferentiation on Day 9 and mesangial cell activation on Day 14. By gene expression analysis arrays, we identified discs-large homolog 1 and angiopoietin-like 4 as potential mediators of the HT effects. In addition, we identified several pathways possibly related to the pleiotropic effects of HT, including growth factor signalling, mammalian target of rapamycin signalling, protein ubiquitination, the Wnt-beta catenin pathway and hypoxia signaling. In summary, treatment with HT, initiated after the induction of disease, ameliorates glomerular and tubulointerstitial damage. We provide the first comprehensive insight into the mechanisms underlying the renoprotective effect of high-dose angiotensin II receptor blockers (ARBs). Our study lays the basis for future investigations on novel pathways affected by ARBs in renal disease.

Uncontrolled home blood pressure in the morning is associated with nephropathy in Japanese type 2 diabetes

The purposes of this study were to investigate the state of blood pressure control level and to investigate the relationship between blood pressure control level and nephropathy in Japanese type 2 diabetes. We measured clinic and home blood pressure in 923 type 2 diabetic patients. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Of all patients, 13.9, 12.6, 13.3, and 60.2% were identified as having CH, WCH, MH, and SH, respectively. The average number of drugs prescribed was 1.8. We assessed the association between blood pressure control level and nephropathy in diabetic patients. The degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in the CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy. It is suggested that more aggressive antihypertensive treatment is recommended to prevent nephropathy in diabetic patients.

Augmented antihypertensive effect of a fixed combination formula of candesartan and hydrochlorothiazide combined with furosemide in a patient on peritoneal dialysis

A 38-year-old female patient on peritoneal dialysis (PD) due to type 1 diabetic nephropathy with a well-preserved residual renal function did not respond well to the conventional antihypertensive therapy consisting of candesartan, furosemide, and bunazosin. Switching candesartan for a fixed combination formula of candesartan plus hydrochlorothiazide (HCTZ) while the rest of the other two agents remained unchanged led to the remarkable reduction in both systolic and diastolic blood pressure (BP) without significant changes in the cardiothoracic ratio (CTR), body weight (BW), and residual renal function. This case suggests that when used in combination, diuretics acting on different functional segment of the nephron hold greater potential for enhanced antihypertensive effect, especially in patients on PD whose residual renal function is well preserved. A small dose of HCTZ with an angiotensin II receptor blocker (ARB) may partially explain the therapeutic benefit of this combination therapy in terms of a reliable hypotensive effect, a better adherence, and fewer side effects.

Epithelial Na+ Channel (ENaC), Hormones, and Hypertension

This minireview examines both the basic science and clinical observations over the past 20 years to show how and why overstimulation of the amiloride-sensitive epithelial Na(+) channel (ENaC) expressed by epithelial principal cells of the renal collecting duct may be responsible for a large portion of hypertension in modern society. This idea is based on the finding that, in Liddle syndrome, a mutation of the beta- and/or gamma-subunits of ENaC produces an activated ion channel, in turn resulting in severe hypertension that is resistant to most forms of conventional antihypertensive therapy. ENaC can also be stimulated to conduct sodium by two hormones: aldosterone and insulin. These hormones are both often elevated in obese individuals with therapy-resistant hypertension. Thus, overstimulation of ENaC by metabolic abnormalities in obese individuals may be a likely cause of the hypertension that accompanies obesity. The molecular mechanisms underlying both Liddle syndrome and obesity-related hypertension are different (i.e. genetic and hormonal, respectively), but both have the same end result, namely increased ENaC activity.

Renoprotective effects of telmisartan in patients with advanced chronic kidney disease

Angiotensin II receptor blockers (ARBs) provide renoprotective effects in patients with mild-to-moderate chronic kidney disease (CKD). However, there have been few reports regarding whether ARBs show clinical efficacy and safety in patients with advanced CKD. Seventy-two hypertensive patients with Stages 3 - 4 CKD receiving no ARBs were enrolled in this study and observed up to 48 months. Telmisartan was added to conventional antihypertensive agents (n = 36, mean estimated glomerular filtration ratio [eGFR] 19.7 ml/min/1.73 m2) whilst the remaining control patients were not treated with ARBs (n = 36, mean eGFR 19.2 ml/min/1.73 m2). Urinary protein excretion, kidney function, and the occurrence of end-stage renal disease requiring renal replacement therapy, hyperkalemia, and death were analyzed. Baseline characteristics of each group were similar. During the observation period, the blood pressures of each group decreased at similar rates. In the telmisartan group, 17 patients (47.2%) were introduced to renal replacement therapy, as compared with 31 patients (86.1%) in the control group (relative risk 0.55, 95% confidence interval 0.19 - 0.92, p < 0.05). Telmisartan significantly reduced proteinuria levels (from 3.47 +/- 3.00 to 2.41 +/- 2.46 g/g . creatinine, p < 0.05) and was associated with a reduction of 49.6% in the decline rate of eGFR. The incidence of major adverse events in both groups was similar. The addition of telmisartan to conventional antihypertensive therapy is associated with significant improvement in kidney outcome without increased incidence of adverse effects, even in patients with advanced CKD.