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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valsartan is a second class of angiotensin II receptor antagonist, indicated for the treatment of hypertension. The objective of the study was to monitor the safety of valsartan using the technique of prescription event monitoring (PEM), in patients who were prescribed this drug by general practitioners (GPs) in England. PEM is a noninterventional observation cohort technique. Exposure data were obtained from dispensed prescriptions issued between December 1996 and November 1998. Outcome data were obtained by sending questionnaires to prescribing GPs. The cohort comprised 12881 patients. Events most frequently reported as suspected adverse drug reactions were malaise/lassitude (37; 0.3% of total cohort), dizziness (19; 0.1%), and unspecified side effects (57; 0.4%). Events with the highest incidence density (ID(1) per 1000 patient-months of treatment) in the first month of treatment were malaise/lassitude (15.6), dizziness (11.8), and headache/migraine (10.9). Most frequent reasons for stopping valsartan were not effective (847; 6.6% of total cohort), malaise/lassitude (265; 21%), and dizziness (146; 1.1%). No unexpected serious adverse events were identified. Other events assessed as possibly related to valsartan use were impotence (37), dizziness (19), cough (9), facial oedema (5), hyperkalaemia (3), and angioneurotic oedema (1). There were four reports of exposure during pregnancy and 203 deaths (1.5%) in this cohort. In conclusion, this study monitored the safety profile of valsartan in a large cohort of patients in general practice in England. No untoward features other than dizziness were identified that were not mentioned in the prescribing guidance.
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PMID:The safety of valsartan: results of a postmarketing surveillance study on 12881 patients in England. 1244 41

Valsartan (Diovan) is a potent, orally active, specific, and highly selective blocker for the AT1-receptor subtype. The antihypertensive effects of oral treatment with valsartan were preclinically demonstrated in the sodium-depleted marmosets, renal hypertensive rats (2K1C), spontaneous hypertensive rats (SHR) and stroke-prone SHR. Moreover, valsartan had protective effects against hypertensive end-organ damage such as cardiac hypertrophy and renal disease. In an investigation of pharmacokinetics and pharmacodynamics in normotensive male volunteers, valsartan was rapidly absorbed with the maximal plasma concentration occurring 2-3 h after oral administration. The elimination half-life was about 4-6 h, valsartan was poorly metabolized, and most of the drug was excreted via feces. Valsartan produced persistent reductions of blood pressure in patients with mild to moderate essential hypertension and had a good safety profile with a wide therapeutic window between the effective pharmacological doses and the toxic doses. Therefore, valsartan is expected to be a safe and effective antihypertensive agent for the treatment of essential and severe hypertension.
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PMID:[Preclinical and clinical profile of Valsartan, a selective angiotensin II type-1 receptor blocker]. 1249 11

Angiotensin II type 1 receptor blockers (ARBs) are generally as effective as angiotensin-converting enzyme (ACE) inhibitors in patients with hypertension. However, inhibition of angiotensin is not achieved completely through the blocking effects of ACE inhibitors, and the possibility of a non-ACE pathway for generation of angiotensin II has important implications for treating cardiovascular disease. The selective quality of ARBs for the angiotensin II type 1 (AT1) receptor may confer an advantage. In a recently reported trial, the ARB valsartan substantially improved patients' New York Heart Association class, clinical signs and symptoms, and quality of life and provided morbidity and mortality benefits in selected patients. Valsartan was recently approved to treat heart failure in patients who cannot be maintained on an ACE inhibitor. As a class, ARBs are well tolerated and have a good safety profile.
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PMID:Therapeutic role of angiotensin II receptor blockers in the treatment of heart failure. 1263 May 86

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

Diovan (valsartan) in dose 160 mg/day was given to 20 patients with mild and moderate arterial hypertension living in the Far North. The treatment was carried out during 4 weeks and its influence on circadian BP, lipid, carbohydrate and water-salt exchange was studied. Antihypertensive activity and tolerance to the medication were also analyzed.
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PMID:[Efficiency of diovan (valsartane) in arterial hypertension patients]. 1287 61

This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0+/-14.3 (mean+/-SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (P<0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P>0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (P<0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.
Hypertension 2003 Sep
PMID:Administration time-dependent effects of valsartan on ambulatory blood pressure in hypertensive subjects. 1287 91

Erectile dysfunction is one of the major obstacles for noncompliance in the antihypertensive treatment. It has been shown that various antihypertensive drugs have a negative influence on sexual activity such as diuretics and beta-blockers. Thus, the purpose of the present study was to evaluate the effect of valsartan, an AT1-receptor antagonist, or its combination with hydrochlorothiazide on sexual activity in hypertensive patients. A total of 2202 patients (mean age 54+/-8 years) with hypertension systolic blood pressure (SBP)> or =140 mmHg, diastolic blood pressure (DBP)> or =95 mmHg), or with pretreated hypertension, were included in the present analysis. Blood pressure was measured at baseline, after 8 and 16 weeks, respectively. Sexual activity was assessed with a questionnaire at each of the three visits. Sexual activity (intercourse per week) was determined in three groups: controls (n=27; conventional therapy); valsartan group (n=1899); valsartan in combination with hydrochlorothiazide (n=276). There were 26 drop outs. SBP (-18.6 mmHg) and DBP (-11.6 mmHg) decreased significantly in all three groups. Sexual activity decreased slightly in controls from 1.3 to 0.9 times per week (NS), whereas it increased in the valsartan group from 1.0 to 1.6 times during follow-up (P<0.0001). Similarly, sexual activity increased in the combination group from 0.9 to 1.3 times per week during follow-up (P<0.0001). No sexual activity was reported by 467 (21%) of the 2202 patients at baseline and 154 (7%) at 16 weeks follow-up (P<0.05). Impaired sexual activity is common in hypertensive patients (app. 20%). Valsartan increases the rate of sexual intercourses per week, whereas conventional therapy affects sexual activity adversely.
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PMID:Sexual activity in hypertensive men. 1287 8

In spite of the well-known contribution of angiotensin II (Ang II) in the pathogenesis of Goldblatt two-kidney one clip (G2K1C) hypertension, the importance of other Ang peptides, such as Ang III, Ang IV or Ang 2-10, is scarcely understood. The functional status of these peptides depends on the action of several aminopeptidases called angiotensinases. The metabolism of Ang III to Ang IV by aminopeptidase M (AlaAP) and of Ang I to Ang 2-10 by aspartyl aminopeptidase (AspAP) was evaluated in the renal cortex and medulla of normotensive (Sham-operated) and hypertensive (G2K1C) rats, treated or not with the AT(1) receptor antagonist valsartan. The results demonstrated a highly significant increase of membrane-bound (MEMB) AlaAP in the cortex of the non-ischemic kidney of G2K1C rats compared with the kidney of normal rats and with the clipped kidney of G2K1C rats. This suggests an increased formation of Ang IV in the non-clipped kidney of G2R1C rats. Valsartan reduced MEMB AlaAP and AspAP activities in the renal cortex of normotensive and in the clipped kidney of hypertensive rats. The reduced metabolism of Ang III may prolong its half-life in valsartan-treated animals. These results suggest a role for AlaAP in renovascular hypertension. In addition, the higher AspAP activity of the renal cortex compared to medulla reflects its relative functional difference between both locations.
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PMID:Angiotensinase activities in the kidney of renovascular hypertensive rats. 1289 63

Both bradykinin B2 and angiotensin II type 2 (AT2) receptors are known to stimulate renal production of nitric oxide (NO). To evaluate the individual contributions of AT2 and B2 receptors to renal NO production, we monitored renal interstitial, stable NO metabolites and cGMP by a microdialysis technique in conscious, bradykinin B2-null and wild-type mice (n=8 in each group) during low sodium intake alone or with the angiotensin AT1 or AT2 receptor blockers, valsartan (0.5 microg/min) or PD123319 (0.15 microg/min), or both. During normal salt intake, renal interstitial fluid NO and cGMP levels in B2-null mice were not different from those of wild-type mice. Low sodium intake increased NO and cGMP in wild-type mice but not in B2-null mice. Valsartan increased NO and cGMP in both wild-type and B2-null mice but to a significantly greater degree in the wild-type than in B2-null mice. PD123319 decreased NO and cGMP in both wild-type and B2-null mice. Combined valsartan and PD123319 decreased NO and cGMP in both wild-type and B2-null mice, but there was no significant difference during combined treatment from their levels after administration of PD123319 alone. Our results indicate that during ingestion of a low-salt diet, production of NO is mediated mainly via the AT2-B2 receptor cascade. Blockade of the AT1 receptor enhances the production of NO via the AT2 receptor in both wild-type and B2-null mice. We conclude that NO can be produced by 2 alternative pathways: directly through the AT2 receptor or indirectly from AT2 receptor stimulation of bradykinin via the B2 receptor.
Hypertension 2003 Oct
PMID:Angiotensin AT2 receptors directly stimulate renal nitric oxide in bradykinin B2-receptor-null mice. 1295 15

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Monotherapy of hypertension is often ineffective, since it controls approximately 50% of the blood pressure of hypertensive patients. For lowering blood pressure to less than 140/90 mmHg (or <130/80 mmHg among people with diabetes or chronic renal disease) according to JNC-7 guidelines, combination therapy of two or more drugs is often necessary. The combination of a diuretic with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is effective and provides the additional benefit of blocking the effects of angiotensin II, which is responsible for cardiovascular remodeling and its complications. ARBs may have an advantage over the ACEIs because they block the action of all angiotensin II directly, whereas ACEIs are ineffective in blocking angiotensin II generated by nonclassical ACE pathways. Valsartan (Diovan, Novartis) is one of the seven currently approved ARBs in the USA for the treatment of hypertension, and it has been shown to be very effective in controlling blood pressure given once-daily in doses of 80-160 or 320 mg. Its fixed combination with hydrochlorothiazide (HCT) is even more effective in controlling blood pressure in 70% of the cases. The most commonly used combinations are valsartan/HCT (Diovan/HCT), 80/12.5 and 160/12.5 mg given once-daily.
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PMID:Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan/HCT). 1503 Feb 62


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