Further evidence that higher statin doses are ineffective

19 October 2006

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.


  1. 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.
  2. 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.
  3. 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.


Competing interests: None declared

Competing interests: None declared

Uffe Ravnskov, independent researcher

Magle Stora Kyrkogata 9, 22350 Lund, Sweden

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