Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms

Okuyama, Harumi; Langsjoen, Per H.; Hamazaki, Tomohito; Ogushi, Yoichi; Hama, Rokuro; Kobayashi, Tetsuyuki; Uchino, Hajime

doi:10.1586/17512433.2015.1011125

Cited by 105 publications

(88 citation statements)

References 49 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…10,11,70,186,241,287,290,291 Following publication of reports of exaggerated side-effect rates, [10][11][12]70 and related media coverage, the Picker Institute conducted in-depth interviews and focus groups with patients, general practitioners, and cardiologists, along with online surveys, in 2015. 292 They found that the adverse media coverage was linked to increased reticence among the doctors to discuss and prescribe statins, and reduced compliance by the patients (including those with preexisting cardiovascular disease) due to raised awareness of perceived side-effects.…”

Section: Public Health Consequences Of Misleading Claims About the Samentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

View full text Add to dashboard Cite

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms SummaryThis review is intended to help clinicians, patients and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomized controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment.Large-scale randomized trial evidence shows that statin therapy reduces the risk of heart attacks, ischaemic strokes and coronary revascularization procedures ("major vascular events") by about one quarter for each mmol/L reduction in low density lipoprotein (LDL) cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (e.g. atorvastatin 40 mg daily, costing about £2 per

show abstract

Section: Public Health Consequences Of Misleading Claims About the Samentioning

confidence: 99%

Interpretation of the evidence for the efficacy and safety of statin therapy

et al. 2016

View full text Add to dashboard Cite

show abstract

“…End points such as re-hospitalization, cardiac events, and non-fatal stroke would then be less objective than mortality rates for CVD or all causes. As pointed out previously [11, 81], the apparent effectiveness of statins for the prevention of ASCVD as reported in the literature changed drastically after new clinical trial regulations came into effect in 2004/2005 in the EU and US. After this point, no significant beneficial effects of statins for lowering objective end points have been reported [11, 81].…”

Section: Critical Review Of the Consensus Statement 2017 Based On Stamentioning

confidence: 90%

“…As pointed out previously [11, 81], the apparent effectiveness of statins for the prevention of ASCVD as reported in the literature changed drastically after new clinical trial regulations came into effect in 2004/2005 in the EU and US. After this point, no significant beneficial effects of statins for lowering objective end points have been reported [11, 81]. There are groups of scientists who claim that statins are effective for the prevention of ASCVD, which is based on meta-analyses including RCT reports published before 2004 – mainly in the 1990s.…”

Section: Critical Review Of the Consensus Statement 2017 Based On Stamentioning

confidence: 90%

A Critical Review of the Consensus Statement from the European Atherosclerosis Society Consensus Panel 2017

Okuyama

Hamazaki²,

Hama³

et al. 2018

Pharmacology

Self Cite

View full text Add to dashboard Cite

Background: The Consensus Statement from the European Atherosclerosis Society (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of clinical studies that low-density lipoprotein (LDL) causes atherosclerotic cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic mutations affecting LDL receptor function were found to cause higher or lower LDL-C levels, which are associated with correspondingly altered ASCVD risk. In prospective cohort studies and randomized controlled trials (RCTs) of statins, a remarkably consistent log-linear association was demonstrated between the absolute magnitude of LDL-C exposure and ASCVD risk. The EAS Statement proposes that any mechanism of lowering plasma LDL concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C. However, as we explain, we do not find this conclusion acceptable. Summary: Our review points out that different interpretations are possible for the results of Mendelian randomization studies. As for prospective cohort studies, many inconsistent reports on the association of LDL-C and ASCVD were disregarded when drafting the Statement, reports with and without genetic factors related to LDL receptor function should be analyzed separately, and the term ASCVD in the Statement is used inappropriately because myocardial infarction and cerebral infarction differ in their association with LDL-C. As for RCTs, clinical reports on statins published before and after the implementation of new regulations affecting clinical trials (2004/2005) should not both be included in meta-analyses because the evaluated efficacy of statins changed markedly, and the irreversible adverse effects of statins need to be evaluated more rigorously now that their mechanisms have been elucidated. Key Messages: Apart from the EAS hypothesis that LDL causes ASCVD, recent pharmacological/biochemical studies, as summarized in this review and elsewhere, have revealed that atherosclerosis is caused by statins taken to lower LDL-C, as well as by warfarin and some types of vegetable fats and oils, in the absence of significantly elevated LDL-C levels. Thus, the promotion of statin treatment by the Statement is rather risky and we do not feel that the conclusions are justified for the prevention of ASCVD.

show abstract

“…Okuyama et al represented a perspective that statins stimulate atherosclerosis and heart failure [17]. The researchers said that statins stop the biosynthesis of vitamin K2 that serves as a cofactor for the activation of matrix Gla-protein.…”

Section: Editorialmentioning

confidence: 99%