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Quantitative evaluation of statin effectiveness versus intolerance and strategies for management of intolerance

  • Handrean Soran
    Affiliations
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    Cardiovascular Research Unit, Manchester University NHS Foundation Trust, Manchester, UK
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  • Michael France
    Affiliations
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    Cardiovascular Research Unit, Manchester University NHS Foundation Trust, Manchester, UK
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  • Safwaan Adam
    Affiliations
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    Cardiovascular Research Unit, Manchester University NHS Foundation Trust, Manchester, UK
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  • Zohaib Iqbal
    Affiliations
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    Cardiovascular Research Unit, Manchester University NHS Foundation Trust, Manchester, UK
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  • Jan H. Ho
    Affiliations
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    Cardiovascular Research Unit, Manchester University NHS Foundation Trust, Manchester, UK
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  • Paul N. Durrington
    Correspondence
    Corresponding author.Cardiovascular Research Group, School of Biomedicine, Core Technology Facility (3rd Floor), University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
    Affiliations
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK
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      Highlights

      • From published controlled studies of statins, more than 75 patients need treatment with statin therapy for 10 years to experience a minor reversible side effect attributable to the statin.
      • The number of patients needing statin treatment to prevent one atherosclerotic cardiovascular disease (ASCVD) event over 10 years is between 3 and 61 depending on ASCVD risk and pre-treatment LDL cholesterol.
      • Statin adverse events of equivalent severity to ASCVD occurr with a frequency of <0.133% over 10 years eroding statin benefit minimally.
      • The most severe complication of SI is discontinuation of effective cholesterol-lowering treatment in patients who might otherwise benefit.
      • When statin intolerance (SI) is encountered, re-challenge is recommended with a statin with the potential to reach the appropriate therapeutic target.

      Abstract

      Background and aims

      There is disquiet about statin effectiveness and side effects in both the medical and lay media.

      Methods

      We searched the literature for reports on the incidence of statin intolerance (SI) in which control rates of similar events were also recorded. The number of people who must receive treatment (NNT) to prevent one atherosclerotic cardiovascular disease (ASCVD) event at 5–50% 10-year risk and LDL cholesterol 2–7 mmol/l was compared with the number of those who would experience harm attributable to statin (NNH). Using a similar method, the effectiveness of various strategies to overcome SI in preventing CVD was then compared.

      Results

      Observational studies with non-randomised control groups report higher rates of statin adverse events than randomised trials. Overall, at least 75 patients must be treated for one to experience a side effect. In contrast, the NNT to prevent one ASCVD event with statins as monotherapy or in combination with other cholesterol-lowering medications to achieve at least 50% decrease in LDL cholesterol and <1.8 mmol/l was between 3 and 61, depending on risk and LDL cholesterol. NNH for adverse events of severity equivalent to ASCVD was >750 (<0.1333%).
      When SI is encountered, the most effective current management for most patients in terms of ASCVD reduction is to rechallenge with low dose potent statin and then up-titrate until the cholesterol target has been achieved with, if necessary, the addition of ezetimibe 10 mg daily.

      Conclusions

      The most severe complication of SI is discontinuation of effective cholesterol-lowering treatment in patients who, by virtue of their CVD risk and cholesterol level, might otherwise benefit.

      Graphical abstract

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