Cardiovasc Drugs Ther (2011) 25:571572 DOI 10.

1007/s10557-011-6338-0

ISCP PRESIDENTS PAGE

High Dose Statin Treatment and New Onset Diabetes

Juan Carlos Kaski

Published online: 14 September 2011 # Springer Science+Business Media, LLC 2011

Recently, results of a meta-analysis of data from five large statin trials indicated that intensive-dose statin therapy (80-mg simvastatin or atorvastatin) was associated with an increased risk of new-onset diabetes (12% increased incidence) compared with moderate-dose (1020 mg simvastatin or atorvastatin or 40 mg pravastatin) treatment. The study, carried out by ISCP expert advisor Kausik K. Ray of St. Georges, University of London, and colleagues, was published in the Journal of the American Medical Association [1]. The meta-analysis included five randomized controlled endpoint trials that recruited >1,000 participants each, who were followed up for more than 1 year and compared intensive-dose statin therapy versus moderate-dose statin treatment. The main findings of this work were that over a weighted mean (SD) follow-up of 4.9 (1.9) years, of 32,752 participants without diabetes at baseline, 2,749 developed diabetes (1,449 were receiving intensive-dose therapy and 1,300 moderate-dose therapy) with two additional cases found in the intensive-dose
J. C. Kaski (*) Cardiovascular Sciences Research Centre, St. Georges, University of London, Cranmer Terrace, London SW17 0RE, UK e-mail: jkaski@sgul.ac.uk

group per 1,000 patient-years. In the whole cohort, 6,684 patients developed cardiovascular events, which were less frequent in the intensive-dose group. The authors reported that odds ratios were 1.12 (95% confidence interval [CI], 1.04 1.22; I2=0%) for new-onset diabetes and 0.84 (95% CI, 0.75 0.94; I2=74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. Of interest to managing clinicians and patients, compared with moderate-dose statin therapy, the number needed to harm per year, for intensive-dose statin therapy, was 498 for newonset diabetes. Side effects associated with the administration of statins are not infrequent, albeit extremely serious or life threatening adverse effects are rare. The risk of myopathy for example, is higher in subjects receiving high-dose simvastatin treatment, i.e. 80-mg and it has been recommended that this high dose should only be used in patients who have been already on it for at least 1 year without signs of muscle injury. However, to put the findings of the metaanalysis [1] in perspective, high-dose statin treatment would be expected to cause an additional 2.0 cases of diabetes but prevent 6.5 cardiovascular events per 1,000 patient-years, compared with the use of moderate doses. This suggests that the cardiovascular benefit associated with the use of statins could still outweigh the increased risk of diabetes. Nevertheless, the results of the meta-analysis [1] clearly indicate that physicians should ensure that statins are prescribed to people who are likely to benefit the most. A view sustained by ISCP in its educational programmes on line. Several questions have been raised by the study [1] and many of these relate to the possible reasons for the increased risk of new-onset diabetes in subjects receiving high dose statin treatment. We need answers as to whether this is a causal relationship or just a chance finding, who are the patients at higher risk - and whether this is an effect linked to the mechanisms leading to myopathy, as suggested by the

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Cardiovasc Drugs Ther (2011) 25:571572

authors. Data from an animal model suggest that statininduced myopathy is associated with the development of muscle insulin resistance, providing a potential mechanism. It will be important also to define whether the finding is dependent on how diabetes was defined in the studies assessed in the meta-analysis. Certainly, serious work needs now to be carried out in real-life patients to confirm or refute the results of the metaanalysis [1], to identify the potential mechanisms involved

and devise strategies to minimize the problem. Cardiovascular therapy societies worldwide, such as ISCP, may have a role to play in this process. Reference
1. Preiss D et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy a meta-analysis. JAMA. 2011;305:255664.