Differential effects of lipophilic and hydrophilic statins on muscle sympathetic nerve activity in heart failure with preserved left ventricular ejection fraction

Tokuhisa, Hideki; Murai, Hisayoshi; Okabe, Yozo; Hamaoka, Takuto; Sugimoto, Hiroyuki; Mukai, Yukinori; Inoue, Oto; Takashima, Shinya; Kato, Takeshi; Usui, Soichiro; Furusho, Hiroshi; Kaneko, Shuichi; Takamura, Masayuki

doi:10.1016/j.autneu.2018.04.006

Cited by 18 publications

(9 citation statements)

References 37 publications

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“…The current study included only patients with reduced ejection fraction, however a crossover study revealed that lipophilic statins had a superior effect on sympathetic nerve activity than that of hydrophilic statin in HF with preserved ejection fraction patients. 52 Their results support our finding regarding higher efficacy of lipophilic statins in HF patients. Further studies may be required to investigate effect of statin types on diastolic dysfunction.…”

Section: Discussionsupporting

confidence: 87%

Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study

Said

Wakeel

Khorshid

et al. 2021

Brit J Clinical Pharma

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Aims There are insufficient direct comparative studies addressing the impact of the type of statin on their respective efficacy in heart failure (HF). The aim of the current study was to compare the effects of lipophilic (atorvastatin) vs hydrophilic (rosuvastatin) on left ventricular function, inflammatory and fibrosis biomarkers in patients with chronic HF. Methods This was a prospective, randomized, comparative, parallel study. A total of 85 patients with chronic HF optimized on guideline directed therapy were randomized to receive either atorvastatin 40 mg (n = 42) or rosuvastatin 20 mg (n = 43) for 6 months. Baseline and follow‐up assessment included 2D echocardiography, measurement of N‐terminal pro‐brain natriuretic peptide, interleukin‐6 and soluble suppression of tumorigenicity 2 (sST2) levels, liver enzymes and lipid profile. Results The increase in left ventricular ejection fraction was significantly higher in the atorvastatin group compared to the rosuvastatin group (6.5% [3–11] vs 4% [2–5], P = .006). The reduction in left ventricular end diastolic and end systolic volume was comparable between the 2 groups. The decrease in sST2 levels in pg/mL was significantly higher in the atorvastatin compared to the rosuvastatin group (−255 [−383 to −109.8 vs − 151 [−216 to −69], P = .003). There was a significant reduction in N‐terminal pro‐brain natriuretic peptide and interleukin‐6 levels in both groups, yet the reduction was comparable in both groups. Conclusion The study results suggest that lipophilic atorvastatin is superior to hydrophilic rosuvastatin in increasing left ventricular ejection fraction and reducing fibrosis marker sST2 in HF patients. Trial registration ID: NCT03255044, registered on 21 August 2017.

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Section: Discussionsupporting

confidence: 87%

Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study

Said

Wakeel

Khorshid

et al. 2021

Brit J Clinical Pharma

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“…In diabetic rats receiving oral atorvastatin, the protein expression of β1-adrenoceptor increased and β1/β3-adrenoceptor ratio changed [ 104 ]. Atorvastatin and simvastatin also improved cognitive performance in a mouse model of spatial memory by modulating β-adrenergic receptors [ 105 ].…”

Section: Effect Of Statins On Ras Pathwaysmentioning

confidence: 99%

Effects of Statins on Renin–Angiotensin System

Kiaie

Gorabi

Reiner

et al. 2021

JCDD

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Statins, a class of drugs for lowering serum LDL-cholesterol, have attracted attention because of their wide range of pleiotropic effects. An important but often neglected effect of statins is their role in the renin–angiotensin system (RAS) pathway. This pathway plays an integral role in the progression of several diseases including hypertension, heart failure, and renal disease. In this paper, the role of statins in the blockade of different components of this pathway and the underlying mechanisms are reviewed and new therapeutic possibilities of statins are suggested.

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“…Pathogenesis of HFpEF may also be driven by several comorbidities such as overweight/obesity, diabetes mellitus, renal dysfunction, and hypertension 87 , as current evidence suggests that statins have been shown to be beneficial in these conditions as well [98][99][100] . Lipophilic statins may have a favorable effect on sympathetic activity in HFpEF, as increased sympathetic activity is associated with the pathogenesis of HFpEF 101 . Further mechanistic studies focusing on the underlying cellular and molecular changes in HFpEF caused by statins are needed.…”

Section: Statins In Heart Failure With Preserved Ejection Fraction: Current Evidencementioning

confidence: 99%

Therapeutic implications of statins in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction: a review of current literature

2021

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Statins are one of the standard treatments to prevent cardiovascular events such as coronary artery disease and heart failure (HF). However, data on the use of statins to improve clinical outcomes in patients with established HF remains controversial. We summarized available clinical studies which investigated the effects of statins on clinical outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Statins possess many pleiotropic effects in addition to lipid-lowering properties that positively affect the pathophysiology of HF. In HFrEF, data from two large randomized placebo-controlled trials did not show benefits of statins on mortality of patients with HFrEF. However, more recent prospective cohort studies and meta-analyses have shown decreased risk of mortality as well as cardiovascular hospitalization with statins treatment. In HFpEF, most prospective and retrospective cohort studies as well as meta analyses have consistently reported positive effects of statins, including reducing mortality and improving other clinical outcomes. Current evidence also suggests better outcomes with lipophilic statins in patients with HF. In summary, statins might be effective in improving survival and other clinical outcomes in patients with HF, especially for patients with HFpEF. Lipophilic statins might also be more beneficial for HF patients. Based on current evidence, statins did not cause harm and should be continued in HF patients who are already taking the medication. Further randomized controlled trials are needed to clarify the benefits of statins in HF patients.

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Differential effects of lipophilic and hydrophilic statins on muscle sympathetic nerve activity in heart failure with preserved left ventricular ejection fraction

Cited by 18 publications

References 37 publications

Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study

Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study

Effects of Statins on Renin–Angiotensin System

Therapeutic implications of statins in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction: a review of current literature

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