Safety and efficacy of aliskiren in the treatment of hypertension: a systematic overview

Angeli, Fabio; Reboldi, Gianpaolo; Poltronieri, Cristina; Verdecchia, Paolo

doi:10.1517/14740338.2012.696608

Cited by 16 publications

(7 citation statements)

References 71 publications

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“…Currently the efficacy and safety of aliskiren is best tested in two clinical trials in heart failure, namely, the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failure (ATMOSPHERE) [28] and the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) [29]. However, on 20 December 2011, the Aliskiren Trial In Type 2 Diabetes Using Cardio-Renal Disease Endpoints (ALTITUDE) [30], was stopped on the recommendation after the second interim efficacy analysis [31], [32]. In this study, aliskiren or placebo was randomly assigned as an adjunct to an ACE inhibitor or ARB to type 2 diabetic patients who are at high risk for cardiovascular and renal events.…”

Section: Discussionmentioning

confidence: 99%

The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy – A Randomized Cross-Over Study

et al. 2013

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BackgroundLaboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy.MethodsWe studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored.ResultsAfter aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p<0.0001), which remained at a low level throughout the treatment period. There was a significant difference in proteinuria between the aliskiren and placebo groups from 4 to 16 weeks after treatment (p<0.01 for all comparisons). After aliskiren treatment, there were modest but statistically significant reductions in eGFR (57.2±29.1 to 54.8±29.3 ml/min/1.73 m2, p = 0.013) and diastolic blood pressure (72.6±12.3 to 66.2±11.2 mmHg, p<0.0001). None of the patient developed severe hyperkalemia (serum potassium ≥6.0 mmol/l) during the study period.ConclusionsAliskiren has anti-proteinuric effect in patients with IgA nephropathy and persistent proteinuria despite ACE inhibitor or ARB. Further studies are needed to confirm the renal protecting effect of direct renin inhibition in chronic proteinuric kidney diseases.Trial Registration ClinicalTrials.gov NCT00870493

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Section: Discussionmentioning

confidence: 99%

The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy – A Randomized Cross-Over Study

et al. 2013

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“…Recent years have seen the development of the nonpeptide, orally long-term effective direct renin inhibitor (DRI), aliskiren, which may block the initial stages of the RAS and exert a sustained antihypertensive action in hypertensive subjects [74–76]. …”

Section: Role Of Renin-angiotensin System In the Regulation Of Normentioning

confidence: 99%

Renin-Angiotensin System and Sympathetic Neurotransmitter Release in the Central Nervous System of Hypertension

Tsuda

2012

International Journal of Hypertension

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Many Studies suggest that changes in sympathetic nerve activity in the central nervous system might have a crucial role in blood pressure control. The present paper discusses evidence in support of the concept that the brain renin-angiotensin system (RAS) might be linked to sympathetic nerve activity in hypertension. The amount of neurotransmitter release from sympathetic nerve endings can be regulated by presynaptic receptors located on nerve terminals. It has been proposed that alterations in sympathetic nervous activity in the central nervous system of hypertension might be partially due to abnormalities in presynaptic modulation of neurotransmitter release. Recent evidence indicates that all components of the RAS have been identified in the brain. It has been proposed that the brain RAS may actively participate in the modulation of neurotransmitter release and influence the central sympathetic outflow to the periphery. This paper summarizes the results of studies to evaluate the possible relationship between the brain RAS and sympathetic neurotransmitter release in the central nervous system of hypertension.

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“…The drug is approved for the treatment of hypertension. Recent clinical trials have shown that the addition of aliskiren to standard therapy with RAS blockade in patients with type 2 diabetes leads to more adverse events [16][17]. However, there have been no controlled studies comparing the therapeutic effects of aliskiren with ARB for the treatment of diabetes targeting the optimal blood pressure level.…”

Section: Introductionmentioning

confidence: 99%

Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial

Uzu

Araki

Kashiwagi³

et al. 2016

PLoS ONE

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BackgroundIn patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity.MethodsWe randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to <30 mg/g of albumin-to-creatinine ratio) or microalbuminuria (30 to <300 mg/g) to the DRI group or ARB group (any ARB) with a target blood pressure of <130/80 mmHg. The primary endpoint was a reduction in albuminuria.ResultsTwelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients.ConclusionDRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.

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Safety and efficacy of aliskiren in the treatment of hypertension: a systematic overview

Cited by 16 publications

References 71 publications

The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy – A Randomized Cross-Over Study

The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy – A Randomized Cross-Over Study

Renin-Angiotensin System and Sympathetic Neurotransmitter Release in the Central Nervous System of Hypertension

Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial

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