Renal and cardio-protective effects of direct renin inhibition: a systematic literature review

Heerspink, Hiddo J.L.; Perkovic, Vlado; Zeeuw, Dick de

doi:10.1097/hjh.0b013e3283310f92

Cited by 27 publications

(6 citation statements)

References 97 publications

(188 reference statements)

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“…NT-proBNP, BNP, PRA, PRC, aldosterone are all biological markers connected tightly with heart failure. Of them, NT-pro BNP and BNP levels are particularly important, and can be used to evaluate the severity of disease [27]. However, when evaluating cardiovascular outcomes in HF patients, our results showed that compared with placebo, aliskiren showed no obvious effects on death rate, the incidence of myocardial infarction and stroke.…”

Section: Main Findings and Possible Explanationsmentioning

confidence: 67%

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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Section: Main Findings and Possible Explanationsmentioning

confidence: 67%

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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“…Alterations in renin activity have been associated with hypertension, salt-sensitivity of blood pressure and responsiveness to anti-hypertensive treatments 1–3 . Therefore, the renin gene (REN) is a rational candidate for unraveling the genetic basis of essential hypertension (EH).…”

Section: Introductionmentioning

confidence: 99%

Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses

Sun

Williams

Pojoga

et al. 2011

J Renin Angiotensin Aldosterone Syst

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The renin gene has been previously reported to be associated with essential hypertension in a variety of ethnic groups. However, no studies have systematically evaluated the relationship between single nucleotide polymorphisms (SNPs) representing coverage of the entire renin gene and hypertension risk. To evaluate the association between renin gene variation and hypertension we investigated data on HyperPath cohort with 570 hypertensive and 222 normotensive Caucasian subjects. Six tagging SNPs and resultant haplotypes were tested for associations with hypertension risk, followed by mean arterial pressure (MAP), plasma renin activity (PRA) and the change in MAP in response to angiotensin II infusion (AngII ΔMAP). The A allele of SNP rs6693954 and the haplotype containing rs6696954A were significantly associated with higher risk for hypertension (OR=1.98, P=0.0001; OR=1.63 P=0.0005, respectively). The same haplotype block was also associated with altered PRA levels and blunted AngII ΔMAP (global P value=0.02, 0.047, respectively). Our results confirm that polymorphisms in the REN are associated with increased risk for hypertension in an independent cohort, and that the underlying mechanism may reside in the interaction of renin activity and vascular responsiveness to angiotensin II.

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“…However, renin inhibitors do regulate renal perfusion. When used either alone or in combination with other RAS inhibitors, direct renin inhibition clearly increases renal plasma flow, reduces albuminuria, and improves cardiovascular parameters such as total peripheral resistance, arterial pressure, and left ventricular mass index [48]. In healthy volunteers, renin inhibitors increase renal blood flow by nearly 70% more than ACE inhibitors [49].…”

Section: Management Of Hypertension In Diabetes: a Microcirculation Amentioning

confidence: 99%

Hypertension Management and Microvascular Insulin Resistance in Diabetes

Cao

Liu

2010

Curr Hypertens Rep

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Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to impaired insulin signaling, reduced nitric oxide availability, and vasoconstriction. Conversely, it acts on the type 2 receptors to cause vasodilatation. Because substrate and hormonal exchanges occur in the microvasculature, antihypertensive agents targeted to improve microvascular insulin sensitivity and function may have beneficial effects beyond their capacity to lower blood pressure in patients with diabetes.

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Renal and cardio-protective effects of direct renin inhibition: a systematic literature review

Abstract: Evidence from preclinical and clinical studies suggests that DRIs may have renal and cardiovascular effects beyond their ability to lower blood pressure. Results of ongoing hard outcome trials are awaited to definitively assess the renal and cardio-protective effects of these agents.

Cited by 27 publications

References 97 publications

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

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

Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses

Hypertension Management and Microvascular Insulin Resistance in Diabetes

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