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Patients with low concentrations of low density lipoprotein (LDL) cholesterol, lowered as a result of taking statins, are at significantly more risk of being diagnosed as having cancer compared with patients with higher concentrations of the cholesterol, according to a meta-analysis of 23 large studies of statins (Journalof the American College of Cardiology 2007;5:409-18).
The analysis found one more case of newly diagnosed cancer per 1000 patients with low achieved LDL cholesterol concentrations who were taking statin treatment (below 100 mg/dl) compared with patients with higher concentrations of the cholesterol (100-150 mg/dl). US guidelines recommend 100 mg/dl.
The study set out to investigate why and how statins sometimes increase concentrations of liver enzymes and cause rhabdomyolysis. Results showed that raised liver enzymes were significantly related to higher doses of statins. The rate of raised liver enzymes was 271 with high dose statin, 195 with intermediate dose, and 114 with low dose statin per 100000 person years for each 10% reduction in LDL cholesterol (P<0.001 for all pairwise comparisons). Rates of rhabdomyolysis were also higher with higher doses of statins, although not significantly so.
The meta-analysis included 23 published trials of different statins used at a range of doses, with at least 1000 person years of follow-up. These included a total of 75117 patients who took statins and cumulative follow-up of 309506 person years.
The researchers found a “disturbing,” highly significant inverse relation between the lowest concentration of LDL cholesterol achieved with statin treatment and the risk of newly diagnosed cancers (R2=0.43, P=0.009). The cancers were of a wide range of types, including genitourinary, prostate, respiratory, and haematological cancer. The researchers saw no significant relation between relative or absolute reduction in LDL cholesterol and rates of cancer.
Richard Karas, professor of medicine at Tufts University School of Medicine in Boston, and lead author of the study, cautioned, “This analysis doesn't implicate the statins in increasing the risk of cancer. However, certain aspects of lowering LDL with statins remain controversial and merit further research,” he said.
The study authors noted, “The body of evidence is reassuring that statin use in itself is not associated with an increased risk of cancer compared with placebo.” But they said that previous studies had not answered the question addressed by their study: what is the relation between reduction of LDL cholesterol in patients treated with statins and incident cancer?
In the light of current feeling that “lower is better” for LDL cholesterol concentrations to reduce cardiovascular risk, the authors warned, “It may be prudent not to use a statin dose beyond what is required to achieve the LDL cholesterol target,” but “evidence is reassuring that statin use in itself is not associated with an increased risk of cancer compared with placebo.”
Another study showed that use of simvastatin was associated with an almost 50% reduction in the risk of Alzheimer's disease and Parkinson's disease and that another statin, atorvastatin, was associated with a “modest” reduction in risk (BMC Medicine 2007;5:20 doi: 10.1186/1741-7015-5-20).
The study analysed data from the decision support system of the US Department of Veterans' Affairs database, which contains diagnostic, medication, and demographic information on 4.5 million people. The association between taking a statin and dementia was examined compared with patients who took cardiovascular drugs other than statins, after adjusting for factors associated with dementia or Parkinson's disease.
Data were obtained for more than 700000 people older than 64 years who were taking simvastatin and more than 50000 people who were taking atorvastatin. The hazard ratios for incident dementia for simvastatin and atorvastatin were 0.46 (95% confidence interval 0.44 to 0.48, P<0.0001) and 0.91 (0.80 to 1.02, P=0.11). Simvastatin also showed a reduced hazard ratio for newly acquired Parkinson's disease (0.51, 0.49 to 0.55, P<0.0001).
“The strength of reduction of incidence of dementia with simvastatin is striking,” said lead author Benjamin Wolozin, professor of pharmacology at Boston University. He added, “The strength of this study is that it examines the issue with a huge amount of statistical power and uses existing data to look prospectively at Alzheimer's [disease] and Parkinson's [disease].”