Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An association has been shown between plasma renin activity (PRA) and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition of angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.
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PMID:The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction. 1918 45

Hypertension is one of the major causes of cardiovascular morbidity. Most patients who are on treatment for hypertension fail to achieve adequate control with the existing therapy and rates of cardiovascular morbidity remain high. As the renin-angiotensin-aldosterone system is strongly implicated in the development of hypertension-related target organ damage, intensive efforts have been devoted towards the development of drugs targeting this system. In addition to angiotensin converting enzyme inhibitors and angiotensin receptor blockers, inhibition of renin has also become a clinical reality. Aliskiren, a novel renin inhibitor, has overcome a number of shortcomings of existing drugs and is now available to address angiotensin production directly at its rate-limiting step.
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PMID:Aliskiren: a novel renin inhibitor for hypertension. 1921 31

Inhibition of renin, the first rate-limiting enzyme in the renin-angiotensin system, has long been a therapeutic goal for treatment of hypertension. Aliskiren, the first in a new class of oral direct renin inhibitors, has been shown to reduce blood pressure (BP) in several short-term studies. In this 52-week, open-label, multicenter, parallel-group study, the long-term safety, tolerability, and efficacy of aliskiren-based therapy were assessed in Japanese patients (N=345) with mild-to-moderate essential hypertension. The study had two periods: (i) an 8-week, dose-titration period and (ii) a 44-week, fixed-dose period with an optional addition of a diuretic or a calcium channel blocker (CCB). Safety was assessed by monitoring all adverse events (AEs), serious AEs (SAEs), vital signs, laboratory parameters, ECGs, and physical examinations. Efficacy was assessed by trough mean sitting BP and responder rate. Aliskiren alone or in combination with a diuretic or a CCB was well tolerated. No deaths were reported during this study. Nine SAEs were reported, and for three of these, a possible relation to the study drug could not be excluded. The overall incidence of AEs was 85.2%, and most of these were mild-to-moderate events such as nasopharyngitis. The incidence of suspected study drug-related AEs was 25.3%. A clinically meaningful reduction of 17.6/12.8 mm Hg from baseline was achieved in the mean sitting BP at the end point with aliskiren, irrespective of the dose and additional treatments. The overall responder rate was 73.3% at the end point. In conclusion, this first long-term study in Japanese patients showed the safety and efficacy of aliskiren-based therapy in mild-to-moderate essential hypertension.
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PMID:Long-term safety, tolerability, and antihypertensive efficacy of aliskiren, an oral direct renin inhibitor, in Japanese patients with hypertension. 1926 78

Aliskiren gained FDA approval for the treatment of hypertension in 2007. It is the first approved pharmaceutical to manage hypertension by direct renin inhibition. With the introduction of novel drugs and mechanisms of action comes the challenge of monitoring for new unreported adverse events. The side effect profile for aliskiren has not yet been fully described. We describe the first apparent report of aliskiren-induced QT prolongation resulting in torsades de pointes.
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PMID:Aliskiren-induced QT interval prolongation. 1927 37

Hypertension is a major risk factor for the development of cardiovascular and renal disease. The incidence of hypertension is increasing globally and the rate of blood pressure control remains inadequate. Renin-angiotensin-aldosterone system (RAAS) plays a crucial role in volume regulation and maintenance of blood pressure. Pathological activation of RAAS results in chronic hypertension and consequent end organ damage. Most patients with hypertension require combination therapy using agents with complimentary mechanisms of action. Hydrochlorothiazide (HCTZ) together with an agent blocking the RAAS such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) are widely used effective anti-hypertensive therapy. Aliskiren is an orally effective direct renin inhibitor that blocks the generation of angiotensin I from angiotensinogen, the rate limiting step of RAAS activation. Studies have shown equivalent antihypertensive efficacy of aliskiren when compared to existing medications such as HCTZ, ACE inhibitors and ARBs. Aliskiren has also been tested in combination therapies. The current review aims to look at the efficacy of aliskiren therapy in hypertension and the evidence for using aliskiren in combination with HCTZ.
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PMID:Renin inhibition with aliskiren in hypertension: focus on aliskiren/hydrochlorothiazide combination therapy. 1933 34

Certain patient populations have a high prevalence of hypertension, including black, elderly, or obese patients; patients with metabolic syndrome, or frank diabetes; and patients with chronic kidney disease. Many of these patients experience renin-angiotensin-aldosterone system (RAAS) dysregulation, which is important because the RAAS plays a pivotal role in the pathogenesis of hypertension, cardiovascular disease, and renal dysfunction. Data available regarding newer approaches that target the RAAS, including direct renin inhibition and aldosterone receptor antagonism, in patients who often have hypertension are reviewed. Aliskiren, the first direct renin inhibitor, is effective in a number of these patient groups, including those who are black or obese or who have metabolic syndrome, renal impairment, or diabetes. In addition, in the setting of long-term angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, aldosterone receptor antagonists (spironolactone and eplerenone) provide another rational therapeutic approach for patients whose blood pressure is not controlled by standard therapies.
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PMID:New therapeutic options in patients prone to hypertension: a focus on direct Renin inhibition and aldosterone blockade. 1939 Apr 29

With the arrival of a new class of drugs for the management of hypertension comes the need to define its role. Aliskiren, an orally administered direct renin inhibitor, has been approved by the US Food and Drug Administration for the treatment of hypertension. Currently, the recommendation for choice of agent in the treatment of uncomplicated hypertension is a thiazide diuretic, and for patients with diabetic nephropathy, heart failure, or coronary artery disease, an angiotensin-converting enzyme inhibitor. Patients for whom an angiotensin-converting enzyme inhibitor is indicated who are intolerant as a result of side effects should take an angiotensin receptor blocker. A new class of medicines that specifically inhibits renin is an exciting addition to the armamentarium in the treatment of hypertension. This article explores the role of aliskiren in treating hypertension as well as its side effects and appropriate dosing.
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PMID:Renin inhibition for hypertension: selecting the right role for a new class of drug. 1943 72

Aliskiren/hydrochlorothiazide is a single-pill combination of the first in the new class of non-peptide direct renin inhibitors (aliskiren) and a thiazide diuretic (hydrochlorothiazide [HCTZ]) that achieves blood pressure (BP) reductions greater than those seen with either component alone. In double-blind, 8-week clinical trials, aliskiren and HCTZ (as a combination of the individual components or as single-pill combinations) reduced mean sitting systolic and diastolic BP from baseline to a significantly greater extent than placebo, aliskiren monotherapy and HCTZ monotherapy. Aliskiren/HCTZ produced additional BP reductions in patients inadequately responsive to 4 weeks' prior treatment with aliskiren or HCTZ alone. Responder rates and BP control rates further demonstrated the benefits of aliskiren/HCTZ combination therapy over monotherapy with individual components in patients with mild to moderate hypertension. Aliskiren plus HCTZ appeared to be effective as long-term (up to 1 year) combination treatment in an open-label trial. In a 12-week placebo-controlled trial in obese patients with hypertension, BP reductions and responder and control rates were significantly greater with aliskiren/HCTZ than with HCTZ alone. Aliskiren/HCTZ was generally well tolerated in clinical trials, with most adverse events being mild and transient in nature.
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PMID:Aliskiren/hydrochlorothiazide combination: in mild to moderate hypertension. 1944 70

The renin-angiotensin-aldosterone system (RAAS) is an important mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons and is a major contributor to hypertension-related target organ damage. The concept of renin inhibition for managing hypertension by blocking the RAAS pathway at its point of activation is very attractive since the renin-angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II). Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs), is approved for the treatment of hypertension. It is effective in reducing BP in the general population of hypertensive patients and in special patient groups such as obese persons, and has a tolerability and safety profile similar to placebo. Aliskiren has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering. It reduces proteinuria in diabetic patients and has favorable neurohumoral effects in patients with symptomatic heart failure. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in the therapeutic armamentarium.
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PMID:Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors. 1947 81

Aliskiren is the first direct renin inhibitor for the treatment of hypertension. Clinical experience from studies in over 14,000 patients has shown that aliskiren, alone or in combination with other antihypertensive therapies, provides effective blood pressure lowering with a good safety and tolerability profile.The ultimate aim of antihypertensive therapy, however, is to reduce the risk of adverse cardiovascular and renal outcomes.The effect of aliskiren on surrogate markers of organ damage and clinical outcomes is being assessed in the ongoing ASPIRE HIGHER programme, the largest clinical trials programme in the cardio-renal disease area. Results from the ALOFT, AVOID and ALLAY studies suggest that aliskiren has positive effects on markers of cardiovascular and renal damage in patients with type 2 diabetes and nephropathy, heart failure and left ventricular hypertrophy.ASPIRE HIGHER also includes four large-scale studies assessing the potential outcome benefits of aliskiren, and the results of these trials will help define the clinical utility of aliskiren in the treatment of cardiovascular and renal diseases. In this article, we review the antihypertensive efficacy of aliskiren and explore its potential in the management of cardiovascular and renal risk.
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PMID:Managing cardiovascular and renal risk: the potential of direct renin inhibition. 1950 53


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