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Efficacy of statins in familial hypercholesterolaemia: a long term cohort study

BMJ 2008; 337 doi: (Published 11 November 2008) Cite this as: BMJ 2008;337:a2423
  1. Jorie Versmissen, researcher1,
  2. Daniëlla M Oosterveer, researcher1,
  3. Mojgan Yazdanpanah, epidemiologist1,
  4. Joep C Defesche, senior researcher2,
  5. Dick C G Basart, clinician3,
  6. Anho H Liem, clinician4,
  7. Jan Heeringa, statistician5,
  8. Jacqueline C Witteman, professor of epidemiology5,
  9. Peter J Lansberg, clinician2,
  10. John J P Kastelein, professor of vascular medicine2,
  11. Eric J G Sijbrands, associate professor1
  1. 1Department of Internal Medicine, Erasmus University Medical Centre, PO box 2040, 3000 CA Rotterdam, Netherlands
  2. 2Department of Vascular Medicine, Academic Medical Centre, PO box 22660, 1100 DD Amsterdam, Netherlands
  3. 3Department of Cardiology, Westfries Gasthuis, PO box 600, 1620 AR Hoorn, Netherlands
  4. 4Department of Cardiology, Oosterschelde Hospital, PO box 106, 4460 BB Goes, Netherlands
  5. 5Department of Epidemiology and Biostatistics, Erasmus University Medical Centre, Rotterdam
  1. Correspondence to: E J G Sijbrands e.sijbrands{at}
  • Accepted 26 October 2008


Objective To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia.

Design Cohort study with a mean follow-up of 8.5 years.

Setting 27 outpatient lipid clinics.

Subjects 2146 patients with familial hypercholesterolaemia without prevalent coronary heart disease before 1 January 1990.

Main outcome measures Risk of coronary heart disease in treated and “untreated” (delay in starting statin treatment) patients compared with a Cox regression model in which statin use was a time dependent variable.

Results In January 1990, 413 (21%) of the patients had started statin treatment, and during follow-up another 1294 patients (66%) started after a mean delay of 4.3 years. Most patients received simvastatin (n=1167, 33 mg daily) or atorvastatin (n=211, 49 mg daily). We observed an overall risk reduction of 76% (hazard ratio 0.24 (95% confidence interval 0.18 to 0.30), P<0.001). In fact, the risk of myocardial infarction in these statin treated patients was not significantly greater than that in an age-matched sample from the general population (hazard ration 1.44 (0.80 to 2.60), P=0.23).

Conclusion Lower statin doses than those currently advised reduced the risk of coronary heart disease to a greater extent than anticipated in patients with familial hypercholesterolaemia. With statin treatment, such patients no longer have a risk of myocardial infarction significantly different from that of the general population.


  • Contributors: JV contributed to the original idea for the study and participated in the statistical analysis and writing the manuscript. DMO, MY, and JCW participated in the statistical analysis and writing the manuscript. JCD and DCGB participated in designing the study and collecting study data. AHL participated in collecting study data and writing the manuscript. JH participated in the statistical analysis and interpreting the data. JJPK initiated the large familial hypercholesterolaemia survey in 1989 in the Netherlands and holds the database of these patients. He also coached the research team and participated in writing of the manuscript. EJGS had the original idea for the study, coached the research team, and participated in writing the manuscript. EJGS is the guarantor of the study, and all authors read the article and approved the published version.

  • Funding: This work was funded by the Netherlands Heart Foundation (2006B190). JJPK and EJGS have received research funding from pharmaceutical manufacturers, but they did not receive industry funding for the present study. All authors declare they are independent from funders.

  • Competing interests: None declared.

  • Ethical approval: The ethics institutional review board of each participating hospital approved the study protocol. All patients gave their informed consent.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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