Intended for healthcare professionals

Rapid response to:

Analysis And Comment Controversy

Should we lower cholesterol as much as possible?

BMJ 2006; 332 doi: (Published 01 June 2006) Cite this as: BMJ 2006;332:1330

Rapid Response:

Re: Surely some mistake? - but does it matter

Pharmacology professor Hughes is evidently correct in
that statins occupy, with various permanency, the active site in the enzyme
resulting in reduced production of mevalonate, the 6 carbon precursor to
the 5 carbon group based isoprenoid family. While interesting, the
point is not how statins don't work but if or why they don't.

Clearly, when there is mathematical certainty from 2 meta analysis [JAMA
and JACC 2004, ref's in (1)] that women don't have a mortality benefit
from a statin or, in secondary prevention, no benefit in myocardial infarction
one has to come with answers why this might be. Why PROSPER found
no mortality benefit in over 70 year olds also needs to be answered first
and, I suggest, before we argue method of action or side-effects from any

I suggest there may be an 'event' benefit in statins in younger males
since statins mimic nitroglycerin [promote the NO-synthase pathway] and
thus lower the rate of 'classic' male stable angina symptoms, arguably
not ever a fatal condition but certainly one that can send one to the cath-lab
while in a trial. Pharmacologists should split out this statin effect as a confounder in combined endpoint studies and then we can see if anyone really benefits from impeding the mevalonate pathway and that affects every
system in the body.

Regarding the 'lower is better' concept, the 1/4 million patient-year observational J-LIT study (2) showed that simvastatin 'hyper-responders'
achieving the LDL levels the various guidelines propose had significantly greater mortality than those remaining near total cholesterol 6 ± 0.5
mmol/L and LDL 4 ± 0.8 mmol/L [J-LIT
graphs from table 5 Medline 12499611]

Eddie Vos- vos{at}

1.) Vos E, Rose CP. Questioning
the benefits of statins
. CMAJ Nov 8, 2005; 173 (10). doi:10.1503/cmaj.1050120.

2.) Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N, Oikawa S
et al Large
scale cohort study of the relationship between serum cholesterol concentration
and coronary events with low-dose simvastatin therapy in Japanese patients
with hypercholesterolemia.
Circ J. 2002 Dec;66(12):1087-95.

Competing interests:
None declared

Competing interests: No competing interests

13 June 2006
Eddie Vos
Sutton (Qc) Canada J0E 2K0