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Original research article
Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease
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  • Published on:
    Re: Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease
    • Ralph K Akyea, Research Associate Division of Primary Care, University of Nottingham, Nottingham, UK
    • Other Contributors:
      • Joe Kai, Clinical Professor and Head of Primary Care
      • Nadeem Qureshi, Clinical Professor
      • Barbara Iyen, Clinical Assistant Professor
      • Stephen F. Weng, Assistant Professor in Integrated Epidemiology and Data Science

    We are grateful for the comments by David P Foley, Zoe Harcombe and Uffe Ravnsker on our paper.

    Both American and UK guidelines for the treatment of cholesterol,[1,2] recommend monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. Our recently published paper [3] examined LDL-C reduction among patients initiating statins in the real-world setting.

    With regard to the points raised:

    Why didn’t you analyse the possible reasons for the observed ‘findings’?

    Our study was not designed to establish causality so we are unable to analyse possible reasons for the observed findings. We are, however, undertaking further research to establish these latter.
    David P Foley notes in his response, ‘it is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect’. However, it is important to avoid any erroneous impression that patients are started on low dose statins in primary care. As shown in Table 1, most patients in this study were actually prescribed moderate and high potency statins (70.9% in the sub-optimal responders compared to 81.8% in the optimal responders).
    A study by Vupputuri et al,[4] examined LDL-C reduction and adherence among high-risk patients initiating statins in a real-world setting using electronic health records of 1,066 patients in the US. Of patients with high adherence...

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    Conflict of Interest:
    NQ is a member of the NICE Familial Hypercholesterolaemia Guideline Development Group (CG71) and NICE Lipid Modification Guidelines Group (CG181). SW is a member of the Clinical Practice Research Datalink (CPRD) Independent Scientific Advisory Committee (ISAC) and previously held an NIHR-SPCR career launching fellowship award. The remaining authors have no competing interests.
  • Published on:
    Why didnt you analyse the possible resons for the observed 'findings' ?
    • David P Foley, Interventional Cardiologist Beaumont Hospital Dublin Ireland

    This study has already been inappropriately quoted in the media which is what the public read and misinformation is propagating. The authors need to take some responsibility for failing to point out that the dosing of the statins prescribed (most likely archaic low dose simvastatin) isn't analysed and long term compliance isn't addressed in this ' primary prevention population based longitudinal non interventional study'
    Cardiologists are going to inundated with questions from patients with coronary disease on statins who have misinterpreted information which is incomplete and misrepresented - the title of the study needs to be highlighted 'Initiation of statins' is well put and needs to be remembered. The study cannot address the 'ongoing management' of cardiovascular risk with appropriate cardiovascular investigation of patients and optimization of preventative strategies as this study does not address this crucial aspect.
    It is already well proven that only moderate to high dose statin therapy has a proven biological anti-atherogenic effect so that low doses initiated in general practice are actually ineffective and this is what the study shows NOT that statins are ineffective but that medical practice of blanket prescribing of low doses of statins is ineffective without monitoring of response and ongoing titration to achieve evidence based targets. This omission from the conclusions needs to be corrected and it ne...

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    Conflict of Interest:
    None declared.
  • Published on:
    This paper needs to be corrected to adjust for lifestyle differences

    The conclusion of this article was twofold: 1) approximately half of primary care patients put on statins did not achieve at least a 40% reduction in LDL-Cholesterol (the sub-optimal group) and 2) those who did (the optimal group) had fewer cardiovascular incidents over the next (approximately six) years.

    Table 1 in the paper shows that the sub-optimal group have 1.43 times the “alcohol misuse” of the optimal group. There is no more information on alcohol consumption beyond this. Were the alcohol misusers also far less likely to be non or moderate drinkers and far more likely to be heavy and frequent drinkers?

    The smoking information shows that, from the limited information available, the sub-optimal group were 25% more likely to be smokers. However, there is no smoking information for 96% of patients. There is no activity information – were the drinking/smokers more likely to be sedentary? Were they more likely to be obese?

    There were more men in the sub-optimal group. The sub-optimal patients were more likely to be poorly-controlled diabetics and less likely to have hypertension treated.

    Correspondence with the researchers confirmed that the HRs in Table 2 were not adjusted for anything other than age and baseline LDL-Cholesterol. They were not adjusted for alcohol misuse, or smoking, or gender, or any other lifestyle factors that were known to be different between the two groups – even with vast amounts of missing information.

    The enti...

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    Conflict of Interest:
    I have written blog posts about cholesterol and/or statins.
  • Published on:
    Questionable Benefit of Increasing the Degree of Cholesterol Lowering
    • Uffe Ravnskov, Independent researcher No affiliayion
    • Other Contributors:
      • Paul J. Rosch, Professor

    In their prospective cohort study of 165,411 primary care patients, Akyea et al. claim that suboptimal responders on statin treatment will experience significantly increased risk of future cardiovascular disease (CVD)(1). As many cardiovascular events may heal without serious health problems, we consider mortality as the most important outcome. Among the 80,802 patients with optimal cholesterol lowering, 821 (1.01 %) died from CVD. Among the 84,609 patients with suboptimal cholesterol-lowering 873 (1.03 %) died. This means that to prevent one cardiovascular death by optimal cholesterol lowering you have to increase the degree of lowering in 5,000 patients for six years. This is hardly a benefit because several independent researchers have reported that serious side effects from statin treatment are much more common than reported in the statin trials (2). The small numbers reported in the trial reports are achieved by excluding participants who suffer from side effects of the drug during a few weeks long run-in period before the start of the trial. That this is an effective method to lower the number of side effects appeared in the IDEAL trial where this method wasn´t used and where a high statin dose was compared with a low dose, because in that trial almost half of the participants in both groups suffered from serious side effects (2).

    Furthermore, Akyea et al. have not reported total mortality in the two groups. This failure may introduce another bias because tota...

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    Conflict of Interest:
    None declared.