Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aliskiren (Rasilez) is the first oral renin inhibitor. Its present indication is essential hypertension, as monotherapy or in combination with other antihypertensive agents (diuretic, calcium antagonist, ...). It may also be associated with an angiotensin converting enzyme inhibitor (or an AT1 angiotensin receptor antagonist) in order to benefit of a dual blockade of the renin-angiotensin-aldosterone system. The usual daily dose is 150 mg, to be increased up to 300 mg if necessary. New clinical trials are ongoing to validate this novel therapeutic approach in other indications such as congestive heart failure and diabetic nephropathy.
 ...
PMID:[Aliskiren (Rasilez), direct renin inhibitor]. 1905 13

This study was conducted to assess the use of angiotensin receptor blockers (ARBs) in European paediatric patients experiencing essential hypertension. This was a retrospective analysis of the IMS MIDAS Prescribing Insight Medical Database. Five major important European markets, including France, Germany, Italy, Spain and the UK were studied for the usage of ARBs as either a monotherapy or fixed-dose combination (FDC) therapy . Paediatric patients with essential hypertension were identified using ICD-10 codes, and anatomical therapeutic chemical (ATC) classification was used to identify major classes of antihypertensives. Projected prescription data for paediatric patients (<18 years) in the time period of October 2005 to September 2006 were analysed. Special emphasis was placed on the category of 6-17 years of age, as many ARBs were recommended in children above 6 years of age. Out of 242,405 estimated paediatric patients with hypertension, 222,033 (91.6%) were diagnosed with essential hypertension. Out of 230,220 projected prescriptions dispensed in these essential hypertensives, approximately 76.2% were for patients in the category of 6-17 years of. In the age group of 6-17 years, ARBs constituted 25.5% of the projected prescriptions, with 10.6% in the form of FDC of ARBs with hydrochlorothiazides (HCTz). Projected ARB prescription usage, either as a monotherapy or as an FDC with HCTz, was higher in Italy (35.7%), France (30.9%) and Spain (28.1%), but was lower in Germany (5.3%), and non-existent in the United Kingdom. Valsartan-based and losartan-based FDCs were commonly used in the age range of 6-17 years, and accounted for 39. and 13.9% of the projected prescription volume in the ARB-FDC category, respectively. In a majority of the important European markets, paediatric hypertensive patients in the age range of 6-17 years are often treated with ARB monotherapy or FDC therapy. Some ARBs lack necessary clinical studies to support its use in treating essential hypertension in paediatric patients.
 ...
PMID:Assessment of the use of angiotensin receptor blockers in major European markets among paediatric population for treating essential hypertension. 1905 66

We conducted a systematic review and meta-analysis of double-blind randomized controlled trials to quantify the dose-related systolic (SBP) and diastolic blood pressure (DBP) lowering efficacy of renin inhibitors vs placebo in the treatment of adults with primary hypertension. Databases searched were Medline (1966-March 2008), EMBASE (1988-March 2008) and Cochrane Central Register of Controlled Trials (CENTRAL). Six trials in 3694 patients met the inclusion criteria. All examined aliskiren, the only renin inhibitor licensed for marketing in Canada and the United States. Aliskiren caused a dose-related SBP/DBP lowering effect compared to placebo: weighted mean difference with 95% CI: aliskiren 75 mg, -2.9 (-4.6, -1.3)/-2.3 (-3.3, -1.3) mm Hg; aliskiren 150 mg, -5.5 (-6.5, -4.4)/-3.0 (-3.7, -2.3) mm Hg; aliskiren 300 mg, -8.7 (-9.7,-7.6)/-5.0 (-5.6, -4.3) and aliskiren 600 mg, -11.4 (-13.5, -9.2)/-6.6 (-7.9, -5.2) mm Hg. Aliskiren 300 mg significantly lowered both SBP -3.0 (-4.0, -2.0) and DBP -1.7 (-2.3, -1.0) as compared to aliskiren 150 mg. Aliskiren has no effect on blood pressure variability. No data were available to assess the effect of aliskiren on heart rate or pulse pressure. This review found weak evidence that during 4- to 8-week use, aliskiren did not increase withdrawals due to adverse effects as compared to placebo. We concluded that aliskiren has a dose-related blood pressure lowering effect better than placebo and magnitude of effect is similar to that determined for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
 ...
PMID:Blood pressure lowering efficacy of renin inhibitors for primary hypertension: a Cochrane systematic review. 1915 26

Cardiovascular risk is subject to circadian variation, with peak morning incidence of myocardial infarction and stroke correlating with the early morning blood pressure (BP) surge (EMBPS). Ideally, antihypertensive therapy should maintain control of BP throughout the 24-h dosing cycle. In two sister studies, Prospective, Randomized Investigation of the Safety and efficacy of Micardis vs Ramipril Using ABPM (ambulatory BP monitoring) (PRISMA) I and II, BP control was compared in patients with essential hypertension (24-h mean baseline ambulatory BP approximately 148/93 mm Hg) randomized to the angiotensin receptor blocker, telmisartan (80 mg; n=802), or the angiotensin-converting enzyme inhibitor, ramipril (5 or 10 mg; n=811), both dosed in the morning. The primary end point was the change from baseline in mean ambulatory systolic BP (SBP) and diastolic BP (DBP) during the final 6 h of the 24-h dosing cycle. The adjusted mean treatment differences in the last 6-h mean ambulatory SBP/DBP were -5.8/-4.2 mm Hg after 8 weeks and -4.1/-3.0 mm Hg after 14 weeks, in favour of telmisartan (P<0.0001 for all four comparisons). Secondary end point results, including the mean 24-h ambulatory BP monitoring, day- and night-time BP and 24-h BP load, also significantly favoured telmisartan (P<0.0001). Both treatments were well tolerated; adverse events, including cough, were less common with telmisartan. These findings suggest that telmisartan is more effective than ramipril throughout the 24-h period and during the EMBPS; this may be attributable to telmisartan's long duration of effect, which is sustained throughout the 24-h dosing period.
 ...
PMID:Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRISMA I and II randomized trials. 1922 30

A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n=30): continuous amlodipine treatment at a stable dose; efonidipine group (n=30): amlodipine (5 mg day(-1)) was changed to efonidipine at a dose of 40 mg day(-1)). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121+/-25 vs. 114+/-21 g m(-2), P<0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension.
 ...
PMID:Long-term effect of efonidipine therapy on plasma aldosterone and left ventricular mass index in patients with essential hypertension. 1949 38

In essential hypertension, endothelial dysfunction has been documented many times and correlates with prognosis. The influence of the renin-angiotensin-aldosterone system (RAAS) on endothelial dysfunction has also been studied. The present study investigated the duration of the effects of RAAS-blocking drugs on endothelial function in 44 consecutive, never-treated, outpatients with mild to moderate hypertension. Patients (11 per group) received an angiotensin receptor blocker (ARB; irbesartan 300 mg/day or valsartan 160 mg/day) or an angiotensin-converting enzyme inhibitor (ACEi; fosinopril 10 mg/day or quinapril 20 mg/day). If target blood pressure (< 140/90 mmHg) was not achieved, 12.5 mg/day hydrochlorothiazide was added. Endothelial function, assessed by measuring brachial artery diameter, did not change significantly after 6 weeks, 1 year or 3 years of treatment in any group. Across all groups, endothelium-dependent and -independent vasodilation increased significantly after 6 weeks but, after 1 year, decreased below baseline and was at a similar level after 3 years; groups did not differ significantly. Both ACEi and ARB had similar effects on endothelial function; improvement occurred at the start of treatment but was not maintained. Endothelial dysfunction may be a resistant or irreversible feature of hypertension, requiring high doses of antihypertensive drugs and above-average patient compliance.
 ...
PMID:Drugs with blocking effects on the renin-angiotensin-aldosterone system do not improve endothelial dysfunction long-term in hypertensive patients. 1976 81

Antihypertensive treatment is an essential, life-prolonging measure in primary hypertension. It prevents apoplexy, myocardial infarction, and hypertensive kidney failure. Chronic kidney failure is associated with hypertension and an accelerated form of arteriosclerosis. Demise from cardiovascular affliction is a leading cause of death in renal patients (chronic renal failure stages II-IV, renal failure requiring dialysis, renal transplantation). What, then, is the role of antihypertensive treatment in such patients, and, specifically, what is achieved by renin-angiotensin-aldosterone (RAA) system modifying agents? Two meta-analyses have recently investigated these issues. An article in The Lancet evaluated eight studies on dialysis patients (n = 1679). It concluded that antihypertensives are beneficial in reducing cardiovascular morbidity and mortality. However, we criticize these conclusions and show that the data are not convincingly in favor of antihypertensive treatment. A meta-analysis in the American Heart Journal assessed the role of antihypertensive agents and RAA system modifying drugs in 45,758 patients (from 25 studies), who were in stages I-III of renal failure, i.e., not (yet) requiring dialysis. The authors claim that angiotensin- -converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) significantly reduced cardiovascular outcomes. However, our analysis of the data is not consistent with their conclusions. It showed that the results were quite mixed, that the authors may have overemphasized the positive results, and that considering all the results, it should be concluded that antihypertensive treatments, including those with ACEI/ARB, may not be superior to placebo (sic!) in renal patients. Rather than doing meta-analyses, larger primary studies are needed to reveal the real role of antihypertensive treatments in renal patients.
 ...
PMID:Should we prescribe blood pressure lowering drugs to every patient with advanced chronic kidney disease? A comment on two recent meta-analyses. 1984 40

The prevalence of hypertension is increasing steadily in the US, particularly among African Americans. It is now clear that a large proportion of patients are inadequately controlled, with many patients requiring at least two agents to achieve their target BP. Calcium channel blockers (CCBs), comprising two subclasses--dihydropyridines and nondihydropyridines--have been for many years one of the mainstays of hypertension therapy. However, the use of CCBs as monotherapy has recently been overshadowed by the introduction of newer classes of agents such as angiotensin receptor blockers. Examining the pharmacologic and clinical effects of CCBs in essential hypertension and among specific patient groups (e.g. African Americans, patients with renal disease) paves the way for understanding why these agents are currently enjoying a resurgence in popularity as the basis for several fixed-dose combination regimens that promise to improve BP control and reduce the risk of cardiovascular events.
 ...
PMID:Calcium channel blockers: their pharmacologic and therapeutic role in hypertension. 1984 47

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day(-1)) was changed to olmesartan given at a dose of 20 mg day(-1). There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135+/-36 vs. 123+/-29 g m(-2); P<0.01).These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.
 ...
PMID:Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension. 1994 30

Aliskiren (Rasilez), a direct renin inhibitor, is currently indicated for the treatment of essential hypertension, as monotherapy or in combination, especially with hydrochlorothiazide (Rasilez HCT). It may also be use to obtain a more complete blockade of the renin-angiotensin-aldosterone system (RAAS) when it is associated with an angiotensin converting enzyme inhibitor (ACEI) (or an AT1 angiotensin receptor antagonist) (ARA). There is some room for agents that may be more efficacious in reducing the progression of diabetic nephropathy than ACEI or ARA. In this context, the dual blockade of RAAS most probably offers a better efficacy than the simple blockade, but also exposes to a higher risk. Should ongoing trials confirm the preliminary favourable results, aliskiren might reach a forefront position among the armamentarium now available to optimize the RAAS blockade. The present article will summarize advances concerning the biochemical effects of the specific mode of action of aliskiren, especially the potential interferences related to increased renin/pro-renin levels, as well as results of recent clinical trials, not only in hypertension, but also in the fields of diabetes, renal insufficiency and cardiology. The objectives and design of the landmark study ALTITUDE will also be briefly presented.
 ...
PMID:[Advances concerning aliskiren, direct renin inhibitor and aliskiren-hydrochlorothiazide]. 2006 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>