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

Antihypertensive drugs that inhibit the renin-angiotensin system (RAS) have been proposed to have additional benefits beyond their classic effects on the cardiovascular system, including reducing the risk of new-onset diabetes. Whether RAS inhibitors vary in ability to protect against new-onset diabetes is, however, unknown. The angiotensin II type 1 receptor (AT(1)) blocker telmisartan has been discovered to also activate the peroxisome proliferator-activated receptor-gamma (PPARgamma), an established antidiabetic drug target. In patients with hypertension and biochemical features of the metabolic syndrome, telmisartan has had beneficial effects on lipid and glucose metabolism. As a selective modulator of PPARgamma, telmisartan does not cause the side effects of fluid retention and weight gain associated with conventional thiazolidinedione ligands of PPARgamma. These observations raise the possibility that combined AT(1) receptor blockade and selective PPARgamma modulation with molecules such as telmisartan could provide greater protection from new-onset diabetes and cardiovascular disease than drugs that target either the RAS or PPARgamma alone. The cardioprotective and antidiabetic effects of telmisartan are being assessed in two large clinical trials, the ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular Disease (TRANSCEND).
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PMID:Beyond the classic angiotensin-receptor-blocker profile. 1858 Aug 62

The development of angiotensin II receptor blockers (ARB) as a new class of drugs for the management of hypertension has elicited the attention of many clinicians worldwide with the aim of improving blood pressure (BP) control as well as cardiovascular protection. Among ARB telmisartan has been shown to be characterised by an antihypertensive efficacy fully covering the 24-hour period, thereby allowing to antagonise the adverse effects of early morning BP rise on cardiovascular risk. Other specific effects of the drug are represented by its favourable metabolic profile (particularly on insulin sensitivity) and neutral effects on sympathetic cardiovascular function. These properties are coupled with cardioprotective effects, documented by the evidence that the drug: 1) is effective in favouring the regression of cardiac and vascular organ damage, 2) reduces arterial stiffness and improves vascular distensibility and 3) reverses the endothelial dysfunction typical of the hypertensive state particularly when complicated by renal failure, diabetes, obesity or metabolic syndrome. Several of these properties can account for the results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), documenting the beneficial effects on the drug on cardiovascular morbidity and mortality.
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PMID:Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension. 1858 82

We conducted comparative analysis of clinico-economical efficacy of angiotensin converting enzyme inhibitors as components of combination therapy of patients with arterial hypertension and ischemic heart disease. Clinical efficacy of fosinopril, moexipril, perindopril, and ramipril was comparable: in compared groups statistically significant lowering of arterial pressure was achieved by day 6 of treatment and this lowering persisted up to day 36 of therapy with ramipril. All studied drugs were well tolerated. Ramipril was notable for highest economical efficacy determined by the method of \"minimization of expenditures\". Technology of assessment of clinico-economical effectiveness of preparations from the same pharmacological group can be used in compilation of standards of drug therapy of various diseases, basing on which a physician administers a concrete drug to a concrete patient.
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PMID:[Clinico-economical efficacy of angiotensin converting enzyme inhibitors in patients with arterial hypertension and ischemic heart disease]. 1872 35

The angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are a well known entity and have been used in therapeutics for various indications like hypertension, myocardial infarction and CHF. However, there is a renewed interest in these compounds in terms of their effects on pain perception in animals as well as in human beings. They have yielded contradictory results, showing hyperalgesia in some studies but analgesia in others. Hence this study was undertaken to evaluate the effect of Ramipril (an ACE-I) and Losartan (an ARB) on pain perception in human volunteers using cola caps and handcuff of sphygmomanometer. A total of 30 healthy, normotensive individuals with no previous history of intake of analgesics during or 4 weeks prior to the study were selected after an informed consent. The first group received a single dose of placebo, the second group received Ramipril (2.5 mg) & the third group received Losartan (50 mg). Pain perception threshold (the point at which an individual first experiences pain) and the maximum tolerated pain were assessed using the above method. The control group showed no significant changes in pain threshold, but the group receiving either Ramipril or Losartan showed a decline in threshold for maximum tolerated pain. Only Ramipril and not Losartan decreased the pain perception threshold. Our study revealed that single dose treatment of healthy volunteers with Ramipril and Losartan may cause algesia as early as after ingestion of the first dose and further studies are needed to study their long term effects on pain perception.
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PMID:Modulation of pain perception by ramipril and losartan in human volunteers. 1883 57

Beneficial effects of an antioxidant (N-acetyl-L-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.
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PMID:Comparative effects of N-acetyl-L-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats. 1901 70

Physicians have embraced the concept of dual renin-angiotensin system (RAS) blockade hoping that it would translate into better blood pressure control as well as incremental nephroprotective and cardioprotective effects. With regard to blood pressure, a small additional fall with dual RAS blockade was observed when compared with that seen in monotherapy. Numerous studies have shown a reduction of albuminuria with dual RAS blockade. However, the recent findings in the ONTARGET (Renal Outcomes With Telmisartan, Ramipril, or Both, in People at High Vascular Risk) study of significantly more doubling of the creatinine and dialysis in the combination arm despite lesser albuminuria emphasized the fallacy of surrogate end points and argue against nephroprotective effects of dual RAS blockade. In heart failure, dual RAS blockade was associated with more hypotension, worsening of renal function, and hyperkalemia than was angiotensin-converting enzyme inhibitor therapy alone. In conclusion, recent outcome and safety data have shattered the halo of dual RAS blockade for hypertension, nephroprotection, and heart failure. Unless data emerge to the contrary, dual RAS blockade should no longer be used in clinical practice.
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PMID:The sudden demise of dual renin-angiotensin system blockade or the soft science of the surrogate end point. 1958 45

Hypertension control in populations, although improving, remains far from satisfactory, even though effective and inexpensive therapies are available. Among many factors responsible for this situation, poor adherence to treatment appears to be particularly important. Unfortunately, even if its causes have been quite well defined, this problem is still far from being solved in clinical practice. The present paper discusses the key issues related to treatment adherence, and discontinuation in hypertension, in the light of recent evidence coming from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease trial (TRANSCEND).
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PMID:Practical aspects of treatment discontinuation and adherence. 1949 17

In patients with arterial hypertension and/or high cardiovascular risk, including patients with diabetes, chronic ischemic heart disease and kidney disease, the risk of heart failure decreases with blood pressure reduction and the use of drugs that inhibit the renin-angiotensin system (RAS) [angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)]. The heart failure incidence seen in ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) is in line with this observation. In ONTARGET, telmisartan and ramipril were equally effective in heart failure prevention and with the same blood pressure reduction. The low event rate, including the low incidence of heart failure in TRANSCEND with the greater use of diuretics in the placebo arm, may help to explain the absence of significant differences between telmisartan and placebo.
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PMID:The question of heart failure in ONTARGET and TRANSCEND: implications for clinical practice. 1949 21

One major element of novelty of the 2007 European guidelines on hypertension refers to the concept of risk categorization, with the aim of obtaining a more precise definition of the hypertensive patient. This has lead to identification of different categories of cardiovascular risk, from the low to the very high. Studies performed in the past few years have shown that the very high risk category is quite common and it is not unusually accompanied by poor blood pressure control. Results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACEI iNtolerant subjects with cardiovascular Disease (TRANSCEND) have allowed us to better define the therapeutic approach to high-risk patients showing the favorable effects of either ramipril or telmisartan on blood pressure control and risk profile. Additionally, these studies have shown that discontinuation of antihypertensive treatment is not a rare phenomenon, which can be at least in part minimized by the use of drugs with a high tolerability profile, such as angiotensin II receptor blockers (ARBs), and more specifically telmisartan. This review article examines in depth the results of the two above-mentioned trials as well as their impact on guidelines on antihypertensive treatment.
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PMID:Implementation of new evidence into hypertension guidelines: the case of the ONTARGET and TRANSCEND trials. 1949 23

The renin-angiotensin system (RAS) plays an important role in the pathogenesis of cardiovascular disease. One of the effects of the activated RAS is target-organ damage, in part due to their effects on causing hypertension. Blocking angiotensin-converting enzyme (ACE) with inhibitors has been shown to attenuate the pathological effects of the RAS. Clinical trials have shown that ACE inhibition improves outcomes in the prevention of acute myocardial infarction, lowering the morbidity and mortality in congestive heart failure, and attenuates renal dysfunction. There is recent evidence to show that angiotensin receptor blockers (ARBs) have similar efficacy to ACE inhibitors in reducing cardiovascular outcomes. The wealth of information obtained regarding the beneficial effects of RAS inhibition on clinical outcome has been focused on monotherapy with either ARB or ACE inhibition. Evidence from some trials suggests that better overall inhibition of RAS by dual therapy may improve clinical outcomes. Combination therapy has been shown to be beneficial in patients with congestive heart failure or renal disease. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial showed equal benefit of either ARB or ACE inhibition with reduction in primary end points in postmyocardial infarction patients, but there was no further benefit from dual therapy in reducing outcomes. In the recent ONTARGET study, there was further evidence that ARBs are equal to ACE inhibitors in reducing cardiovascular events. In Ongoing Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events (ONTARGET), combined RAS blockade did not have any added benefit but resulted in increased risk of adverse outcomes. In the Candesartan in Heart Failure (CHARM) and the Valsartan Heart Failure Trial (Val-HeFT) trials of patients with severe heart failure, the addition of an ARB to an ACE inhibitor reduced cardiac mortality and lowered hospital admissions. Whether or not dual therapy is beneficial in patients with diabetic renal failure should be clarified by future studies. Overall, patients receiving dual therapy, if clinically justified, should be monitored closely for potential adverse effects.
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PMID:Blocking the renin-angiotensin system: dual- versus mono-therapy. 1950 82


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