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    "Legacy effects" of statin therapy in ASCOT-LLA: 14% reduction in all-cause mortality
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    BillH99 posted:
    Paris, France - Long-term results of the Anglo-Scandinavian Cardiac Outcomes—Lipid-Lowering Arm (ASCOT-LLA) study, eight years after the trial officially stopped, showed that treatment with 10 mg of atorvastatin (Lipitor, Pfizer) reduced all-cause mortality compared with placebo, mainly through a reduction in noncardiovascular deaths [1 >.Presenting the results at a hot-line session today at the European Society of Cardiology (ESC) 2011 Congress , investigators observed that reductions in the risk of death from respiratory illness and infection contributed to the overall reduction in all-cause mortality. "The numbers are large, the data are convincing, but we have no definitive explanation to date for the hypothesized legacy effect of atorvastatin on noncardiovascular-death risk reduction," said lead investigator Dr Peter Sever (Imperial College, London, UK).
    The study was published online August 28, 2011 in the European Heart Journal to coincide with the ESC presentation.


    ASCOT-LLA and the long-term effects of atorvastatin



    The results of ASCOT-LLA were first presented and simultaneously published online in the Lancet in 2003 [2 >. As reported by heartwire , lipid lowering with atorvastatin resulted in a significant 36% reduction in the primary end point of fatal coronary heart disease and nonfatal MI after a median follow-up of 3.3 years. At the time the study was stopped, there was a nonsignificant trend toward reduction in all-cause mortality. Upon completion of ASCOT-LLA, investigators continued to collect mortality data and evaluated the mortality outcomes in participants originally randomized to atorvastatin or placebo in the ASCOT-LLA arm for a median of 11 years.
    At the end of the extended follow-up, all-cause mortality was significantly reduced by 14% (hazard ratio [HR> 0.86; 95% CI 0.76-0.98), and noncardiovascular mortality was significantly reduced by 15% (HR 0.85; 95% CI 0.73-0.99). There was no difference in death from cardiovascular causes.
    Looking more closely at deaths from noncardiovascular causes, investigators found that deaths due to cancer were not statistically significant between those treated with atorvastatin vs placebo. There was, however, a significant 36% reduction in deaths due to infection and respiratory illness (HR 0.64; 95% CI 0.42-0.97), driven primarily by deaths due to infection.
    During the session, Sever noted there are emerging data on the effects of statins on infection, with preclinical studies showing statins modulate neutrophil function, reduce proinflammatory cytokine release, improve vascular function, have antithrombotic properties, and improve outcomes from pneumonia and sepsis. Results of other observational studies have suggested that prior statin use also reduces mortality from sepsis. Despite these observations, Sever said that there is still the possibility of confounding bias in some of the observational studies that have shown a benefit of statins in pneumonia and sepsis and that caution should be used when interpreting such results until a randomized clinical trial is performed.
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