Further evidence that higher statin doses are ineffective
In
their recent subgroup analysis of the TNT trial Deedwania and coworkers found
that coronary patients with the metabolic syndrome gained more benefit from
high-dose atorvastatin therapy than coronary patients without, but they didn´t
mention that the latter group gained no benefit at all (table 1). The small
differences between the low-dose and the high-dose groups were far from
significant in this subgroup implying that there is no reason to increase
atorvastatin by eight times in the absence of the metabolic syndrome.
As total mortality was unchanged in all
subgroups, the question is if the significant, but small reduction of non-fatal
events in the patients with the metabolic syndrome offsets possible long-term
side effects. Of special concern is the risk of peripheral neuropathy. In one study the odds ratio for that risk in patients treated with
statins for longer than two years was 26.4 (17.8-45.4)2 and in
another one polyneuropathy was seen in five of 50 cardiology clinic patients
after 28 months of treatment.3 Most likely the risk is even larger in
diabetic patients, and as the symptoms may be seen as part of their disease and
not as a side effect of the treatment this tormenting plague may become
permanent.
Event
rate (%)
10
mg of Atorvastatin
80
mg of Atorvastatin
Major
cardiovascular events
181/2186
(8.3)
172/2231
(7.7)
Major
coronary events
138/2186
(6.3)
134/2231
(6.0)
All-cause
mortality
104/2186
(4.8)
114/2231
(5.1)
Table
1. Primary outcomes in the TNT trial in patients with coronary heart disease
after exclusion of patients with the metabolic syndrome.
References
Deedwania
P, Barter P, Carmena R, et al. Reduction of low-density lipoprotein
cholesterol in patients with coronary heart disease and metabolic syndrome:
analysis of the Treating to New Targets study. Lancet
2006;368:919-28.
Gaist
D, Jeppesen U, Andersen M, Garcia Rodriguez LA, Hallas J, Sindrup SH.
Statins and risk of polyneuropathy: a case-control study. Neurology
2002;58:1333-7.
Langsjoen
PH, Langsjoen JO, Langsjoen AM, Lucas LA. Treatment
of statin adverse effects with supplemental Coenzyme Q10 and statin drug
discontinuation. Biofactors
2005;25:147-52.
Rapid Response:
Further evidence that higher statin doses are ineffective
In
their recent subgroup analysis of the TNT trial Deedwania and coworkers found
that coronary patients with the metabolic syndrome gained more benefit from
high-dose atorvastatin therapy than coronary patients without, but they didn´t
mention that the latter group gained no benefit at all (table 1). The small
differences between the low-dose and the high-dose groups were far from
significant in this subgroup implying that there is no reason to increase
atorvastatin by eight times in the absence of the metabolic syndrome.
As total mortality was unchanged in all
subgroups, the question is if the significant, but small reduction of non-fatal
events in the patients with the metabolic syndrome offsets possible long-term
side effects. Of special concern is the risk of peripheral neuropathy.
In one study the odds ratio for that risk in patients treated with
statins for longer than two years was 26.4 (17.8-45.4)2 and in
another one polyneuropathy was seen in five of 50 cardiology clinic patients
after 28 months of treatment.3 Most likely the risk is even larger in
diabetic patients, and as the symptoms may be seen as part of their disease and
not as a side effect of the treatment this tormenting plague may become
permanent.
Event
rate (%)
10
mg of Atorvastatin
80
mg of Atorvastatin
Major
cardiovascular events
181/2186
(8.3)
172/2231
(7.7)
Major
coronary events
138/2186
(6.3)
134/2231
(6.0)
All-cause
mortality
104/2186
(4.8)
114/2231
(5.1)
Table
1. Primary outcomes in the TNT trial in patients with coronary heart disease
after exclusion of patients with the metabolic syndrome.
References
P, Barter P, Carmena R, et al. Reduction of low-density lipoprotein
cholesterol in patients with coronary heart disease and metabolic syndrome:
analysis of the Treating to New Targets study. Lancet
2006;368:919-28.
D, Jeppesen U, Andersen M, Garcia Rodriguez LA, Hallas J, Sindrup SH.
Statins and risk of polyneuropathy: a case-control study. Neurology
2002;58:1333-7.
PH, Langsjoen JO, Langsjoen AM, Lucas LA. Treatment
of statin adverse effects with supplemental Coenzyme Q10 and statin drug
discontinuation. Biofactors
2005;25:147-52.
Competing interests:
None declared
Competing interests: No competing interests