Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients

Okada, Yoshiyuki; Shibata, Shigeki; Fujimoto, Naoki; Best, Stuart; Levine, Benjamin D.; Fu, Qi

doi:10.1152/ajpregu.00125.2017

Cited by 6 publications

(7 citation statements)

References 46 publications

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“…As can be seen from Figure 7 , aliskiren did not affect LV SV, EDV and ESV, which is consistent with clinical trials ( Solomon et al, 2011 ; Okada et al, 2017 ). In our case, EF also did not change in treatment with aliskiren, in accordance with a number of experimental studies ( McMurray et al, 2008 ; Solomon et al, 2011 ; Pitt et al, 2011 ).…”

Section: Resultssupporting

confidence: 88%

Mathematical modeling of antihypertensive therapy

et al. 2022

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Hypertension is a multifactorial disease arising from complex pathophysiological pathways. Individual characteristics of patients result in different responses to various classes of antihypertensive medications. Therefore, evaluating the efficacy of therapy based on in silico predictions is an important task. This study is a continuation of research on the modular agent-based model of the cardiovascular and renal systems (presented in the previously published article). In the current work, we included in the model equations simulating the response to antihypertensive therapies with different mechanisms of action. For this, we used the pharmacodynamic effects of the angiotensin II receptor blocker losartan, the calcium channel blocker amlodipine, the angiotensin-converting enzyme inhibitor enalapril, the direct renin inhibitor aliskiren, the thiazide diuretic hydrochlorothiazide, and the β-blocker bisoprolol. We fitted therapy parameters based on known clinical trials for all considered medications, and then tested the model’s ability to show reasonable dynamics (expected by clinical observations) after treatment with individual drugs and their dual combinations in a group of virtual patients with hypertension. The extended model paves the way for the next step in personalized medicine that is adapting the model parameters to a real patient and predicting his response to antihypertensive therapy. The model is implemented in the BioUML software and is available at https://gitlab.sirius-web.org/virtual-patient/antihypertensive-treatment-modeling.

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Section: Resultssupporting

confidence: 88%

Mathematical modeling of antihypertensive therapy

et al. 2022

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“…However, since aliskiren has the possibility to increase the risk of hypotension and hyperkalaemia, it may be expected to apply for HF patients who are suffered from hypertension or hypokalaemia at the same time [32]. Moreover, a small-scale published RCT has initially shown that aliskiren lowered arterial stiffness and left ventricular diastolic function in elderly hypertensive patients during a follow-up of 6 months [33].…”

Section: Main Findings and Possible Explanationsmentioning

confidence: 99%

Clinical efficacy, safety and tolerability of Aliskiren Monotherapy (AM): an umbrella review of systematic reviews

Zhao

Shen

et al. 2020

BMC Cardiovasc Disord

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Background: Aliskiren is a newly developed drug. Its role in lowering BP has been recognized. However, the role of aliskiren in treating heart and renal diseases are still controversial. Objective: To evaluate the existing evidence about clinical efficacy, safety and tolerability of aliskiren monotherapy (AM). Methods: An umbrella review of systematic reviews of interventional studies. We searched Pubmed, Embase and Cochrane Library up to June 2019. Two reviewers applied inclusion criteria to the select potential articles independently. The extract and analyze of accessible data were did by two reviewers independently too. Discrepancies were resolved with discussion or the arbitration of the third author. Results: Eventually, our review identified 14 eligible studies. Results showed that for essential hypertension patients, aliskiren showed a great superiority over placebo in BP reduction, BP response rate and BP control rate. Aliskiren and placebo, ARBs or ACEIs showed no difference in the number or extent of adverse events. For heart failure patients, AM did not reduce BNP levels (SMD-0.08, − 0.31 to 0.15) or mortality rate (RR 0.76, 0.32 to 1.80), but it decreased NT-proBNP (SMD-0.12, − 0.21 to − 0.03) and PRA levels (SMD 0.52, 0.30 to 0.75), increased PRC levels (SMD-0.66, − 0.8 to − 0.44). For patients who are suffered from hypertension and diabetes and/or nephropathy or albuminuria at the same time, aliskiren produced no significant effects (RR 0.97, 0.81 to 1.16). Conclusion: We found solid evidence to support the benefits of aliskiren in the treatment of essential hypertension, aliskiren can produce significant effects in lowering BP and reliable safety. However, the effects of aliskiren in cardiovascular and renal outcomes were insignificant. Trial registration: Study has been registered in PROSPERO (CRD42019142141).

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“…Firstly, a RAAS inhibitor may not suit all heart failure patients. Since aliskiren has been associated with adverse events such as hypotension and hyperkalaemia, it may be best indicated for the heart failure patients who have a past history of hypertension and laboratory examination of hypokalaemia [ 18 ]. Most studies of our meta-analysis have included heart failure with reduced ejection patients.…”

Section: Discussionmentioning

confidence: 99%

Aliskiren for heart failure: a systematic review and meta-analysis of randomized controlled trials

et al. 2017

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ObjectiveTo systematically review and synthesize the currently available evidence of aliskiren for the treatment of heart failure.Materials and MethodsWe systematically searched the Cochrane, Embase and PubMed databases to identify the randomized controlled trials (RCT) on the effects of aliskiren on heart failure. Data were synthesized with random effects model and presented in forest plot. Publication bias was evaluated with funnel plot. Heterogeneity was evaluated with Begg's test and Egger's test.ResultsOf 124 studies, 6 RCT of 9845 heart failure patients were included for meta-analysis, including 3727 patients receiving aliskiren. Compared with the controls, aliskiren did not significantly reduce the all-cause mortality (1.02 [0.91–1.14], I2 = 0%) or cardiovascular mortality (1.02 [0.88–1.17], I2 = 7.3%) of heart failure patients. Total adverse events, renal dysfunction, hypotension and hyperkalaemia were not significantly different between the aliskiren group and control group. Begg's test and Egger's test indicated low heterogeneity. Funnel plots indicated low publication bias.ConclusionsAliskiren, either used alone or combined with standard medical therapy, does not significantly reduce the all-cause mortality or cardiovascular mortality of heart failure patients. Although aliskiren does not cause statistically higher adverse events, its adverse events may not be neglected.

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Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients

Cited by 6 publications

References 46 publications

Mathematical modeling of antihypertensive therapy

Mathematical modeling of antihypertensive therapy

Clinical efficacy, safety and tolerability of Aliskiren Monotherapy (AM): an umbrella review of systematic reviews

Aliskiren for heart failure: a systematic review and meta-analysis of randomized controlled trials

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