Efficacy of statins in familial hypercholesterolaemia: a long term cohort study
BMJ 2008; 337 doi: https://doi.org/10.1136/bmj.a2423 (Published 11 November 2008) Cite this as: BMJ 2008;337:a2423
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In a cohort study of the efficacy of statin treatment on risk of
coronary heart disease in patients with familial hypercholesterolaemia,
Versmissen and colleagues’ report that 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
(1). These results match the results from the Simvastatin vs Therapeutic
Lifestyle Changes and Supplements: Randomized Primary Prevention Trial,
which show a potential beneficial effect of food supplements and lifestyle
changes on managing hyperlipidemia (2). In the latter study, the achieved
results with red yeast rice containing monacolins equivalent of low doses
of lovastatin is identical to the results from therapeutic doses of statin
for primary prevention (3). The conclusions reached in the two studies are
intriguing and show some potential for lowering the statin dose or
starting food supplements containing monocolins instead. This will lead to
the reduction of side effects of statin treatment and will improve the
compliance.
References
1. Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart
DCG, Liem AH, et al. Efficacy of statins in familial
hypercholesterolaemia: a long term cohort study. BMJ 2008;337:a2423. (11
November.) [Full text]
2. Becker DJ, Gordon RY, Morris PB, Yorko J, Gordon YJ, Li M, et al.
Simvastatin vs therapeutic lifestyle changes and supplements: randomized
primary prevention trial. Mayo Clin Proc. 2008;83(7):758-764. [Full text]
3. Yovchevski PH, Doncheva NI. Low-Dose Statin Concentration in Red
Yeast Rice: A Confounding Effect on Outcome? Mayo Clin Proc. 2008;83:1187.
[Full text]
Competing interests:
None declared
Competing interests: No competing interests
I read with interest the article by Versmissen and colleagues (1). I
was wondering if the authors have ever performed liver function tests in
the patients during the study. Statins usages are associated with abnormal
liver function tests. While the result shows the reduction in the risk of
coronary heart diseases, nobody knows whether the patients develop active
liver diseases. These would definitely involve the ethical issues. Liver
enzymes should be checked prior to commencing statins therapy, 6–8 weeks
after treatment, annually thereafter, and withdrawn statins if the
transaminases rise to three times the upper limit of normal.
Reference
1. Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart
DCG, Liem AH, et al. Efficacy of statins in familial
hypercholesterolaemia: a long term cohort study. BMJ 2008; 337: a2423
Competing interests:
None declared
Competing interests: No competing interests
Is statin treatment effective in familial hypercholesterolaemia?
In
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
disease.3
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?
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.
Committee on behalf of the Simon Broome Register Group. Mortality in treated
heterozygous familial hypercholesterolaemia: implications for clinical
management. Atherosclerosis 1999;142:105-12.
medical science ignore the past? BMJ 208;37:648.
Association Between Statins and Cancer Incidence in a Veterans Population. J
Natl Cancer Inst. 2008;100:972-3.
K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with
simvastatin and ezetimibe in aortic stenosis. N
Engl J Med 2008;359:1343-56.
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