Rapid Response to Ravnskov's article "Should we lower cholesterol as much as possible?"
We agree with Ravnskov et al that little is known about the adverse
effects of high dose statins but would also propose that little is
known about the long term safety of more modest doses used at present.
Lifetime use of statins may equate to therapy for thirty years or more.
As stated by the authors, multi centre large-scale trials have established
efficacy of these agents but are much less reliable for detection of
infrequent serious adverse outcomes such as cancer.
Recent studies provide reassurance regarding the safety of statins
with respect to all-cause carcinogenicity in the short term[3,4] and up to
ten years. However, whilst the length of post-marketing surveillance
remains quite short compared to the medically accepted latency period for
cancer of twenty years, it seems prudent to establish systems examining
and linking large databases to allow extended follow-up for malignancy.
Such monitoring can also help ascertain whether any class effect or dose-
response exists and whether certain categories of carcinogenicity are
influenced by statins either favourably (as suggested by some case-control
studies) or deleteriously. These data linkage systems should include a
variety of stakeholders, among them regulatory authorities from different
countries and the pharmaceutical industry, all cooperating in the
provision of more robust information in this and other important areas of
pharmacovigilance. Recent issues surrounding the long term uncertainty of
COX-2 inhibitors and hormone replacement therapy have highlighted that
medication safety must be proven rather than assumed, especially for very
widely used medications utilised for long-term therapy.
Corresponding author: Steven Joseph Haas -
1. Ravnskov U, Rosch PJ, Sutter MC, Houston MC. Should we lower
cholesterol as much as possible? BMJ 2006;332(7553):1330-2.
2. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs.
3. 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.
4. Kaye JA, Jick H. Statin use and cancer risk in the General
Practice Research Database. Br J Cancer 2004;90(3):635-7.
5. Strandberg TE, Pyorala K, Cook TJ, Wilhelmsen L, Faergeman O,
Thorgeirsson G, et al. Mortality and incidence of cancer during 10-year
follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet
Steven Joseph Haas has received assistance via an Australian National Health and Medical Research Council Public Health Postgraduate Research Scholarship, Scholarship application I.D. #237059. As corresponding author, Steven Joseph Haas had full access to all data in the study and had final responsibility for the decision to submit for publication.
Andrew Tonkin has received funding for studies and speakers fees from pharmaceutical industry companies including AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, and Sankyo.
Mark Nelson has received funding for studies and consultancies from pharmaceutical industry companies including AstraZeneca, Bayer AG, Sanofi-Aventis, Sanofi-Synthelabo, Bristol-Myers Squibb, Merck Sharp and Dohme, and Pfizer.
John McNeil has served on advisory boards for Pfizer, GlaxoSmithKline, Johnson & Johnson, Bristol-Myers Squibb, Schering-Plough, Sanofi-Aventis, and Merck Sharp and Dohme.
Competing interests: No competing interests