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Trends in statin therapy initiation during the period 2000–2010 in Israel

  • Pharmacoepidemiology and Prescription
  • Published:
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Abstract

Purpose

The aim of this population-based study is to describe trends in the characteristics and treatment patterns of statin initiators over the first decade of the 21st century.

Methods

New statin use was studied retrospectively using the database of Maccabi Healthcare Services (MHS), a large Israeli health maintenance organization. Statin initiators were defined as MHS members aged ≥30 years who first purchased statins between 2000 and 2010. The starting dose was calculated in simvastatin equivalents based on the World Health Organization’s daily defined dose index. Persistence was calculated as the percentage of days covered (PDC) with statins during the first year of therapy.

Results

Statin initiation peaked in 2005 and decreased from 38.6 to 18.6 per 1,000 in the period 2005–2010. The average age at therapy initiation decreased from 58.9 (±12.0) to 54.5 (±11.7) years, and the average (SD) baseline low-density lipoprotein cholesterol (LDL-C) decreased from 4.2 (±1.1) to 4.0 (±0.9) mmol/l during the study period. Women were on average 3 years older than men at treatment initiation, with a higher baseline LDL-C. Among statin initiators, the prevalence of ischemic heart disease (IHD) decreased from 17.8 to 6.7 %, and diabetes prevalence increased from 8.6 to 15.7 %, peaking in 2008 (18.0 %). The PDC with statins ranged between 52.9 and 57.7 %. Simvastatin use at initiation increased from 27.5 % in 2000 to >90 % since 2002. Starting dose increased from 18.5 (±8.9) to 24.3 (±13.7) mg simvastatin equivalent.

Conclusions

Among the study population, statin initiators were increasingly characterized by a lower cardiovascular risk—namely, younger individuals without IHD and with a lower baseline LDL-C. These trends underscore the important shift towards statin initiation for primary prevention, as well as the need to balance between benefits and the potential side effect of statins.

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References

  1. Lewis SJ (2011) Lipid-lowering therapy: Who can benefit? Vasc Health Risk Manag 7:525–534

    Article  PubMed Central  PubMed  Google Scholar 

  2. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S (2013) Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013(1):CD004816

  3. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ (2004) Implications of recent clinical trials for the national cholesterol education program adult treatment panel iii guidelines. J Am Coll Cardiol 44:720–732

    Article  PubMed  Google Scholar 

  4. National Cholesterol Education Program (NCEP) (2001) Summary of the third report of the national cholesterol education program (ncep) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii). JAMA 285:2486–2497

    Article  Google Scholar 

  5. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D; ECS Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees (2011) ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 32:1769-1818

  6. Tabenkin H, Lahav A (eds) (2013) Recommendations of the Israeli Task Force on health promotion and preventive medicine. Israel Medical Association and Israel Association of Family Medicine Physicians, Jerusalem

  7. Gotto AM Jr, Moon JE (2012) Recent clinical studies of the effects of lipid-modifying therapies. Am J Cardiol 110:15A–26A

    Article  PubMed  CAS  Google Scholar 

  8. Cholesterol Treatment Trialists’ (CTT) Collaborators (2010) Efficacy and safety of more intensive lowering of ldl cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376:1670–1681

    Article  CAS  Google Scholar 

  9. Wallach Kildemoes H, Vass M, Hendriksen C, Andersen M (2012) Statin utilization according to indication and age: A Danish cohort study on changing prescribing and purchasing behaviour. Health Policy 108:216–227

    Article  PubMed  Google Scholar 

  10. Larsen J, Andersen M, Kragstrup J, Gram LF (2001) Changes in the utilisation of lipid-lowering drugs over a 6-year period (1993–1998) in a Danish population. Eur J Clin Pharmacol 57:343–348

    Article  PubMed  CAS  Google Scholar 

  11. Walley T, Folino-Gallo P, Stephens P, Van Ganse E (2005) Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997–2003. Br J Clin Pharmacol 60:543–551

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Deambrosis P, Saramin C, Terrazzani G, Scaldaferri L, Debetto P, Giusti P, Chinellato A (2007) Evaluation of the prescription and utilization patterns of statins in an Italian local health unit during the period 1994–2003. Eur J Clin Pharmacol 63:197–203

    Article  PubMed  Google Scholar 

  13. Mamdani MM, Tu JV (2001) Did the major clinical trials of statins affect prescribing behaviour? CMAJ 164:1695–1696

    PubMed Central  PubMed  CAS  Google Scholar 

  14. Mant A, Lowinger J, Hall W, Whicker S, Ringland C, Stark H (2007) Statins down under. Br J Clin Pharmacol 63:125–127

    Article  PubMed Central  PubMed  Google Scholar 

  15. Jackevicius CA, Cox JL, Carreon D, Tu JV, Rinfret S, So D, Johansen H, Kalavrouziotis D, Demers V, Humphries K, Pilote L (2009) Long-term trends in use of and expenditures for cardiovascular medications in Canada. CMAJ 181:E19–28

    Article  PubMed Central  PubMed  Google Scholar 

  16. Li M, Ong KL, Tse HF, Cheung BM (2010) Utilization of lipid lowering medications among adults in the united states 1999–2006. Atherosclerosis 208:456–460

    Article  PubMed  CAS  Google Scholar 

  17. Ruokoniemi P, Helin-Salmivaara A, Klaukka T, Neuvonen PJ, Huupponen R (2008) Shift of statin use towards the elderly in 1995-2005: A nation-wide register study in finland. Br J Clin Pharmacol 66:405–410

    Article  PubMed Central  PubMed  Google Scholar 

  18. Mantel-Teeuwisse AK, Klungel OH, Verschuren WM, Porsius AJ, de Boer A (2002) Time trends in lipid lowering drug use in the Netherlands. Has the backlog of candidates for treatment been eliminated? Br J Clin Pharmacol 53:379–385

    Article  PubMed Central  PubMed  Google Scholar 

  19. Geleedst-De Vooght M, Maitland-van der Zee AH, Schalekamp T, Mantel-Teeuwisse A, Jansen P (2010) Statin prescribing in the elderly in the Netherlands: A pharmacy database time trend study. Drugs Aging 27:589–596

    Article  PubMed  Google Scholar 

  20. Upmeier E, Korhonen MJ, Helin-Salmivaara A, Huupponen R (2013) Statin use among older Finns stratified according to cardiovascular risk. Eur J Clin Pharmacol 69:261–267

    Article  PubMed  CAS  Google Scholar 

  21. Rikala M, Huupponen R, Helin-Salmivaara A, Korhonen MJ (2013) Channeling of statin use towards low-risk population and patients with diabetes. Basic Clin Pharmacol Toxicol 113:173–178

    Google Scholar 

  22. Ministry of Health, State of Israel (1994) National Health Insurance Act 1994. Ministry of Health, Jerusalem

  23. Bendelac J (2011) Membership in sick funds 2010. National Insurance Institute, Jerusalem

    Google Scholar 

  24. Chodick G, Heymann AD, Shalev V, Kookia E (2003) The epidemiology of diabetes in a large Israeli HMO. Eur J Epidemiol 18:1143–1146

    Article  PubMed  Google Scholar 

  25. Shalev V, Chodick G, Goren I, Silber H, Kokia E, Heymann AD (2011) The use of an automated patient registry to manage and monitor cardiovascular conditions and related outcomes in a large health organization. Int J Cardiol 152:345–349

    Article  PubMed  Google Scholar 

  26. Chodick G, Shalev V, Gerber Y, Heymann A, Silber H, Simah V, Kokia E (2008) Long-term persistence with statin treatment in a not-for-profit health maintenance organization: A population-based retrospective cohort study in Israel. Clin Ther 30:2167–2179

    Article  PubMed  Google Scholar 

  27. Caetano P, Lam J, Morgan S (2006) Toward a standard definition and measurement of persistence with drug therapy: Examples from research on statin and antihypertensive utilization. Clin Ther 28:1411–1424

    Article  PubMed  Google Scholar 

  28. WHO Collaborating Centre for Drug Statistics Methodology (2011) Guidelines for ATC classification and DDD assignment, 14th edn. WHO Collaborating Centre for Drug Statistics Methodology Nydalen

  29. Stone NJ, Robinson J, Lichtenstein AH, Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC, Jr., Watson K, Wilson PW (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. Circulation [Epub ahead of print]

  30. Goff DC, Jr., Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Sr., Gibbons R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson J, Schwartz JS, Shero ST, Smith SC, Jr., Sorlie P, Stone NJ, Wilson PW (2013) 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. Circulation doi: 10.1161/01.cir.0000437741.48606.98

  31. Ioannidis JA (2013) More than a billion people taking statins?: Potential implications of the new cardiovascular guidelines. JAMA doi: 10.1001/jama.2013.284657

  32. Jotkowitz AB, Novack V, Rabinowitz G, Segal AR, Weitzman R, Porath A (2008) A national study on lipid management. Eur J Intern Med 19:356–361

    Article  PubMed  CAS  Google Scholar 

  33. Porath AR G, Raskin-Segal A, Weitzman R (2006) Quality clinical primary healthcare indicators in Israel, public report 2003–2005. Israel Ministry of Health, Israel National Institute for Health Policy and Health Services Research, Jerusalem

  34. Manor OSA, Ben-Yehuda A, Paltiel O, Calderon R, Jaffe DH (2012) National program for quality indicators in community healthcare in Israel report, 2008–2010. Israel School of Public Health and Community Medicine, Hebrew University-Hadassah, Jerusalem

    Google Scholar 

  35. Friedman NL, Kokia E, Shemer J (2003) Health value added (hva): Linking strategy, performance, and measurement in healthcare organizations. Isr Med Assoc J 5:3–8

    PubMed  Google Scholar 

  36. Teeling M, Bennett K, Feely J (2005) The influence of guidelines on the use of statins: Analysis of prescribing trends 1998–2002. Br J Clin Pharmacol 59:227–232

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Sheppard JP, Singh S, Fletcher K, McManus RJ, Mant J (2012) Impact of age and sex on primary preventive treatment for cardiovascular disease in the West Midlands, UK: Cross sectional study. BMJ 345:e4535

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  38. Shalev V, Goldshtein I, Porath A, Weitzman D, Shemer J, Chodick G (2012) Continuation of statin therapy and primary prevention of nonfatal cardiovascular events. Am J Cardiol 110:1779–1786

    Article  PubMed  CAS  Google Scholar 

  39. Shalev V, Chodick G, Silber H, Kokia E, Jan J, Heymann A (2009) Continuation of statin treatment and all-cause mortality: A population-based cohort study. Arch Intern Med 169:260–268

    Article  PubMed  Google Scholar 

  40. Shalev V, Goldshtein I, Halpern Y, Chodick G (2013) Association between persistence with statin therapy and reduction in low-density lipoprotein cholesterol level: Analysis of real-life data from community settings. Pharmacotherapy. doi: 10.1002/phar.1326

  41. Lutski M, Shalev V, Porath A, Chodick G (2012) Continuation with statin therapy and the risk of primary cancer: A population-based study. Prev Chronic Dis 9:E137

    Article  PubMed Central  PubMed  Google Scholar 

  42. Chodick G, Amital H, Shalem Y, Kokia E, Heymann AD, Porath A, Shalev V (2010) Persistence with statins and onset of rheumatoid arthritis: A population-based cohort study. PLoS Med 7:e1000336

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  43. Shalev V, Chodick G, Heymanna AD, Kokia E (2005) Gender differences in healthcare utilization and medical indicators among patients with diabetes. Public Health 119:45–49

    Article  PubMed  CAS  Google Scholar 

  44. Guedes AM, Neves PL (2012) Statins for renal patients: A fiddler on the roof? Int. J Nephrol 806872

  45. [No authors listed] (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian simvastatin survival study (4s). Lancet 344:1383–1389.

    Google Scholar 

  46. Heart Protection Study Collaborative Group (2002) Mrc/bhf heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial. Lancet 360:7–22

    Article  Google Scholar 

  47. Collins R, Armitage J, Parish S, Sleigh P, Peto R (2003) Mrc/bhf heart protection study of cholesterol-lowering with simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial. Lancet 361:2005–2016

    Article  PubMed  Google Scholar 

  48. Slanar O, Perlik F (2006) Time trend analysis and variations in statins prescribing in the Czech Republic. Prague Med Rep 107:365–369

    PubMed  CAS  Google Scholar 

  49. Mitchell AP, Simpson RJ (2012) Statin cost effectiveness in primary prevention: A systematic review of the recent cost-effectiveness literature in the United States. BMC Res Notes 5:373

    Article  PubMed Central  PubMed  Google Scholar 

  50. Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Peto R, Collins R (2010) Intensive lowering of ldl cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: A double-blind randomised trial. Lancet 376:1658–1669

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

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Authors and Affiliations

  1. Medical Division, Maccabi Healthcare Services, 27 Ha’Mered Street, Tel Aviv, 68125, Israel

    Varda Shalev, Clara Weil, Raanan Raz, Inbal Goldshtein, Dahlia Weitzman & Gabriel Chodick

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Varda Shalev & Gabriel Chodick

Authors
  1. Varda Shalev
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  2. Clara Weil
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  3. Raanan Raz
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  4. Inbal Goldshtein
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  5. Dahlia Weitzman
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  6. Gabriel Chodick
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Corresponding author

Correspondence to Clara Weil.

Additional information

Varda Shalev and Clara Weil contributed equally to this work.

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Shalev, V., Weil, C., Raz, R. et al. Trends in statin therapy initiation during the period 2000–2010 in Israel. Eur J Clin Pharmacol 70, 557–564 (2014). https://doi.org/10.1007/s00228-013-1637-y

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  • DOI: https://doi.org/10.1007/s00228-013-1637-y

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