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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

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Is statin treatment effective in familial hypercholesterolaemia?

their cohort study of statin efficacy in familial hypercholesterolaemia (FH)
Versmissen et al claimed that such treatment was followed by a 76 % risk
reduction of coronary heart disease (CHD).1 However, they have
disregarded that heart mortality in FH is strongly and inversely associated with
age. In the Simon Broome Register Group study, relative risk of CHD for age
20-39 was 84.3,  plummeted to 5.3
for age 40-59, and was only 1.2 for those age 60 or older.2 The
explanation that those with the highest cholesterol had died early is invalid,
because many studies, including that of Versmissen et al., have found no
difference in mean LDL cholesterol between those with and without cardiovascular

That the relative risk after age 55 was close to that of the general
population may therefore not have been due to treatment, but rather to the
unexplained benefit of being older.  A
similar bias was introduced in their calculation of heart mortality in the
untreated and treated periods, since the mean age before treatment was on
average eight years lower than afterwards.

In the Simon Broome cohort study CHD mortality decreased significantly
after the introduction of statins in patients aged 20-39, but not in the older
cohorts.2 The questionable benefit of statin treatment in middle-aged,
and especially elderly FH patients, must therefore be balanced against potential
side effects. Of particular concern is that an increased incidence of cancer has
been reported in most animal experiments, in five statin trials, in one cohort
and in one case-control study.4,5 Many cohort studies have found that
low cholesterol is a risk factor for cancer, which might explain why cancer
mortality is significantly lower in FH, even after treatment.6 But
will this cardioprotection persist after lifelong statin use?


  1. Versmissen J,
    Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, et al.
    Efficacy of statins in familial hypercholesterolaemia: a long term cohort
    study. BMJ. 2008;337:a2423.
    doi: 10.1136/bmj.a2423.
  2. Scientific Steering
    Committee on behalf of the Simon Broome Register Group. Mortality in treated
    heterozygous familial hypercholesterolaemia: implications for clinical
    management. Atherosclerosis 1999;142:105-12.
  3. Ravnskov U. Should
    medical science ignore the past? BMJ 208;37:648.
  4. Ravnskov U. Re: The
    Association Between Statins and Cancer Incidence in a Veterans Population. J
    Natl Cancer Inst. 2008;100:972-3.
  5. Rossebø AB, Pedersen TR, Boman
    K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with
    simvastatin and ezetimibe in aortic stenosis.
    Engl J Med 2008;359:1343-56.
  6. Neil HA, Hawkins MM,
    Durrington PN, Betteridge DJ, Capps NE, Humphries SE, et al. Non-coronary
    heart disease mortality and risk of fatal cancer in patients with treated
    heterozygous familial hypercholesterolaemia: a prospective registry study.
    Atherosclerosis 2005;179:293-7.

Competing interests:
None declared

Competing interests: No competing interests

24 November 2008
Uffe Ravnskov
independent researcher
Malcolm Kendrick , Paul J. Rosch
Magle Stora Kyrkogata 9, 22350 Lund, Sweden