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Unmet Patient Need in Statin Intolerance: the Clinical Characteristics and Management

Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Purpose

A substantial percentage of patients report intolerance or side effects of statin treatment leading to treatment changes or discontinuation. The purpose of this study was to examine statin therapy changes and subsequent effects on low-density lipoprotein cholesterol (LDL-C) among patients with statin intolerance (SI).

Methods

We identified 45,037 adults from Kaiser Permanente Southern California with SI documented between 2006 and 2012. Changes in statin therapy in the year before and after the SI index date were examined. We categorized patients into those who initiated statin therapy, discontinued, up-titrated, down-titrated, or did not switch therapy. We calculated the percentage change in LDL-C from the year before to the year after SI, and the percentage of patients attaining LDL-C < 100 and < 70 mg/dL.

Results

In the year prior to the SI date, 77.8% of patients filled a statin prescription. Following SI, 44.6% had no treatment change, 25.5% discontinued, and 30.0% altered their statin therapy. Of those who altered statin therapy, 52.6% down-titrated and 17.2% up-titrated their dose. Rhabdomyolysis was documented in < 1% of the cohort. The largest changes in LDL-C were experienced by patients who were on a high-intensity statin then discontinued treatment (35.6% increase) and those who initiated a high-intensity statin (25.5% decrease). The proportion of patients achieving LDL-C < 100 mg/dL and LDL-C < 70 mg/dL was the lowest among those who discontinued therapy.

Conclusions

Although adjustments to the statin dosage may be appropriate upon documentation of SI, many of these patients will have high LDL-C. Strategies for LDL-C reduction in patients with SI may be necessary.

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References

  1. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889–934.

    Article  PubMed  Google Scholar 

  2. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78.

    Article  CAS  PubMed  Google Scholar 

  3. Rosenson RS, Baker SK, Jacobson TA, Kopecky SL, Parker BA. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S58–71.

    Article  PubMed  Google Scholar 

  4. Wei MY, Ito MK, Cohen JD, Brinton EA, Jacobson TA. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J Clin Lipidol. 2013;7(5):472–83.

    Article  PubMed  Google Scholar 

  5. Zhang H, Plutzky J, Shubina M, Turchin A. Continued statin prescriptions after adverse reactions and patient outcomes: a cohort study. Ann Intern Med. 2017;167(4):221–7.

    Article  PubMed  Google Scholar 

  6. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36(17):1012–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rosenson RS. Current overview of statin-induced myopathy. Am J Med. 2004;116(6):408–16.

    Article  CAS  PubMed  Google Scholar 

  8. Rosenson RS, Baker S, Banach M, Borow KM, Braun LT, Bruckert E, et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70(10):1290–301.

    Article  PubMed  Google Scholar 

  9. Banach M, Rizzo M, Toth PP, Farnier M, Davidson MH, Al-Rashidi K, et al. Statin intolerance—an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch Med Sci. 2015;11(1):1–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hovingh GK, Gandra SR, McKendrick J, Dent R, Wieffer H, Catapano A, et al. Identification and management of patients with statin-associated symptoms in clinical practice: a clinician survey. Atherosclerosis. 2016;245:111–7.

    Article  CAS  PubMed  Google Scholar 

  11. Kopecky S, Baum S, Foody JM, et al. Insights into statin intolerance. Clin Cardiol. 2015;38(9):520–6.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tompkins R, Schwartzbard A, Gianos E, Fisher E, Weintraub H. A current approach to statin intolerance. Clin Pharmacol Ther. 2014;96(1):74–80.

    Article  CAS  PubMed  Google Scholar 

  13. Stone NJ, Robinson JG, Lichtenstein AH, Goff DC Jr, Lloyd-Jones DM, Smith SC Jr, et al. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. Ann Intern Med. 2014;160(5):339–43.

    Article  PubMed  Google Scholar 

  14. Awad K, Mikhailidis DP, Toth PP, Jones SR, Moriarty P, Lip GYH, et al. Efficacy and safety of alternate-day versus daily dosing of statins: a systematic review and meta-analysis. Cardiovasc Drugs Ther. 2017;31(4):419–31.

    Article  CAS  PubMed  Google Scholar 

  15. Pencina MJ, Navar-Boggan AM, D’Agostino RB Sr, Williams K, Neely B, Sniderman AD, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370(15):1422–31.

    Article  CAS  PubMed  Google Scholar 

  16. Koebnick C, Langer-Gould AM, Gould MK, Chao CR, Iyer RL, Smith N, et al. Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data. Perm J. 2012;16(3):37–41.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB Sr, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2935–59.

    Article  PubMed  Google Scholar 

  18. Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61.

    Article  CAS  PubMed  Google Scholar 

  19. Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006;28(1):26–35.

    Article  CAS  PubMed  Google Scholar 

  20. Saeed B, Wright E, Evans M, Lewis M, Steinbuhl S. Prevalence of statin intolerance in a high risk cohort and management strategies in contemporary cardiology. Clin Med Res. 2013;11(3):136.

    Article  PubMed Central  Google Scholar 

  21. Mampuya WM, Frid D, Rocco M, Huang J, Brennan DM, Hazen SL, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J. 2013;166(3):597–603.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kones R, Rumana U. Current treatment of dyslipidemia: evolving roles of non-statin and newer drugs. Drugs. 2015;75(11):1201–28.

    Article  CAS  PubMed  Google Scholar 

  23. Graham JH, Sanchez RJ, Saseen JJ, Mallya UG, Panaccio MP, Evans MA. Clinical and economic consequences of statin intolerance in the United States: results from an integrated health system. J Clin Lipidol. 2017;11(1):70–79 e71.

    Article  PubMed  Google Scholar 

  24. Serban MC, Colantonio LD, Manthripragada AD, Monda KL, Bittner VA, Banach M, et al. Statin intolerance and risk of coronary heart events and all-cause mortality following myocardial infarction. J Am Coll Cardiol. 2017;69(11):1386–95.

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was funded by a contractual agreement between the Southern California Permanente Medical Group and Amgen Corporation.

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Authors and Affiliations

  1. Department of Research and Evaluation, Kaiser Permanente Southern California, 100 S. Los Robles, 2nd Floor, Pasadena, CA, 91101, USA

    Teresa N. Harrison, Jin-Wen Y. Hsu, Rong Wei & Kristi Reynolds

  2. Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, USA

    Robert S. Rosenson

  3. School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA

    Emily B. Levitan & Paul Muntner

  4. College of Pharmacy, Western University, Pomona, CA, USA

    T. Craig Cheetham

  5. West Los Angeles Medical Center, Kaiser Permanente Southern California, Los Angeles, CA, USA

    Ronald D. Scott

Authors
  1. Teresa N. Harrison
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  2. Jin-Wen Y. Hsu
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  3. Robert S. Rosenson
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  4. Emily B. Levitan
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  7. Rong Wei
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  9. Kristi Reynolds
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Corresponding author

Correspondence to Kristi Reynolds.

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Conflict of Interest

Teresa N. Harrison, Jin-Wen Y. Hsu, Rong Wei, and Ronald D. Scott declare that they have no conflict of interest. Robert S. Rosenson has received research grants from Akcea, Amgen, Astra Zeneca, Medicines Company, and Regeneron, speaker honorarium from Kowa and Pfizer, royalties from UpToDate, and is a member of advisory boards for Amgen, C5, CVS Caremark, Easy Vitals, Regneron, and Sanofi. Emily B. Levitan has received research funding from Amgen Inc., served on advisory boards for Amgen, and consulted for research projects funded by Novartis. T. Craig Cheetham has received research support from Bristol Myers-Squibb and Pfizer. Kristi Reynolds and Paul Muntner have received research support from Amgen.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent was not required.

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Harrison, T.N., Hsu, JW.Y., Rosenson, R.S. et al. Unmet Patient Need in Statin Intolerance: the Clinical Characteristics and Management. Cardiovasc Drugs Ther 32, 29–36 (2018). https://doi.org/10.1007/s10557-018-6775-0

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  • DOI: https://doi.org/10.1007/s10557-018-6775-0

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