Switching statins: an appropriate guideline for clinical practice?
EDITOR - The June 10 issue of BMJ contained an editorial by J. Moon
and R. Bogle (1) entitled “Switching statins”. The editorial claims that
simvastatin 40 mg has the same lipid lowering effect as 10-20 mg
atorvastatin. However, the trials cited found atorvastatin superior to
simvastatin in lowering LDL-C. Therefore, the suggestion to replace
atorvastatin 10-20 with simvastatin 40 might not be appropriate since
clinical evidence points to the advantage of lowering cholesterol as far
as possible (2).
The editorial mentions a meta-analysis by the authors, based on RCT using
simvastatin 40 and atorvastatin 10, which found no difference between the
two molecules as regards total mortality, fatal coronary disease or
stroke. It is worth noting that in populations with stable ischemic heart
disease, clinical trials testing long-term statins, even at high doses,
have not found any reduction in cardiovascular mortality considered alone;
this might be because of the numbers of events. They did, however, find a
reduction in fatal and non-fatal events cumulatively (3).
The evidence of equivalence, therefore, mentioned in the editorial does
not appear comparable, as the trials with atorvastatin 10 mg (ASCOT-LLA
and CARDS) were in primary prevention, whereas those with simvastatin (4S
and HPS) were mainly for secondary prevention. Then there is also the
question of the duration. Both CARDS and ASCOT-LLA had a shorter median
follow-up than 4S and HPS (3.9 vs. 5 years). We have, however, to note
that the effect, in terms of reduction of events, rises with the duration
of treatment.(4)
It therefore seems clear that combining various studies with differences
in design, duration and types of patient is not really correct from the
methodological point of view, and is an inappropriate basis for guidelines
for clinical practice. The suggestion that one statin should automatically
be used in place of another, on the basis of equivalence that has not
really been demonstrated, is quite likely to be a source of harm to
patients, requiring them to return to their previous therapy, but with the
additional costs for seeking and correcting the damage.
2. Cannon C P, Braunwald E, McCabe C, Rader D J, Rouleaua J L, Belden R,
et al. Intensive versus moderate lipid lowering with statins after acute
coronary syndromes.
N Engl J Med 2004;350:1495-1504
3. Pedersen TR, Faergeman O, Kastelein JJP, Olsson AG, Tikkanen MJ, Holme
I, et al. High-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary
Prevention After Myocardial Infarction. The IDEAL Study: A Randomized
Controlled Trial. JAMA 2005; 294:2437-2445
4. Law MR, Wald NJ and Rudnicka A R. Quantifying effect of statins on low
density lipoprotein cholesterol, ischaemic heart disease, and stroke:
systematic review and meta-analysis. BMJ 2003;326:1423
Competing interests:
None declared
Competing interests:
No competing interests
26 October 2006
Michele Cortellaro
Professor of Internal Medicine, Head of Medical Clinic
Marco Cambielli, Secretary of Italian Society of Medical Education in General Practice, Milan
Milan University, L. Sacco Hospital, Via GB Grassi 74, 20157 Milan Italy
Rapid Response:
Switching statins: an appropriate guideline for clinical practice?
EDITOR - The June 10 issue of BMJ contained an editorial by J. Moon
and R. Bogle (1) entitled “Switching statins”. The editorial claims that
simvastatin 40 mg has the same lipid lowering effect as 10-20 mg
atorvastatin. However, the trials cited found atorvastatin superior to
simvastatin in lowering LDL-C. Therefore, the suggestion to replace
atorvastatin 10-20 with simvastatin 40 might not be appropriate since
clinical evidence points to the advantage of lowering cholesterol as far
as possible (2).
The editorial mentions a meta-analysis by the authors, based on RCT using
simvastatin 40 and atorvastatin 10, which found no difference between the
two molecules as regards total mortality, fatal coronary disease or
stroke. It is worth noting that in populations with stable ischemic heart
disease, clinical trials testing long-term statins, even at high doses,
have not found any reduction in cardiovascular mortality considered alone;
this might be because of the numbers of events. They did, however, find a
reduction in fatal and non-fatal events cumulatively (3).
The evidence of equivalence, therefore, mentioned in the editorial does
not appear comparable, as the trials with atorvastatin 10 mg (ASCOT-LLA
and CARDS) were in primary prevention, whereas those with simvastatin (4S
and HPS) were mainly for secondary prevention. Then there is also the
question of the duration. Both CARDS and ASCOT-LLA had a shorter median
follow-up than 4S and HPS (3.9 vs. 5 years). We have, however, to note
that the effect, in terms of reduction of events, rises with the duration
of treatment.(4)
It therefore seems clear that combining various studies with differences
in design, duration and types of patient is not really correct from the
methodological point of view, and is an inappropriate basis for guidelines
for clinical practice. The suggestion that one statin should automatically
be used in place of another, on the basis of equivalence that has not
really been demonstrated, is quite likely to be a source of harm to
patients, requiring them to return to their previous therapy, but with the
additional costs for seeking and correcting the damage.
REFERENCES
1. Moon JC, Bogle RG. Switching statins. BMJ 2006;332:1344-5.
2. Cannon C P, Braunwald E, McCabe C, Rader D J, Rouleaua J L, Belden R,
et al. Intensive versus moderate lipid lowering with statins after acute
coronary syndromes.
N Engl J Med 2004;350:1495-1504
3. Pedersen TR, Faergeman O, Kastelein JJP, Olsson AG, Tikkanen MJ, Holme
I, et al. High-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary
Prevention After Myocardial Infarction. The IDEAL Study: A Randomized
Controlled Trial. JAMA 2005; 294:2437-2445
4. Law MR, Wald NJ and Rudnicka A R. Quantifying effect of statins on low
density lipoprotein cholesterol, ischaemic heart disease, and stroke:
systematic review and meta-analysis. BMJ 2003;326:1423
Competing interests:
None declared
Competing interests: No competing interests