Statins and sepsis
Brisbane, Australia
* E-mail: peter_kruger{at}health.qld.gov.au
Editor—We congratulate Gao and colleagues1 on the timely review of the place of statin therapy in sepsis. We agree that further prospective clinical research is required to evaluate the potential benefits and limitations of statin use in patients with sepsis and that must specifically address both current statin users and patients not taking statin therapy.
Stopping established statin therapy in patients with acute coronary disease,2 recent major vascular surgery,3 or recent stroke4 has been suggested to be associated with worse outcomes. This has not been specifically assessed in patients with sepsis, although a retrospective study5 in patients with bacteraemia showed continuing statin use after bacteraemia was associated with significantly reduced mortality. These findings suggest that stopping concurrent statin therapy in sepsis (as recommended by current prescribing guidelines) may be associated with increased mortality. These findings require further evaluation in an appropriate prospective randomized trial.
Although the available evidence suggests that the potential for statins as adjuvant therapy in sepsis should be tested, we believe that an international multicentre trial with mortality as an endpoint would be premature. Preliminary data on absorption, pharmacokinetics, physiological effects, and possible adverse effects in critically ill patients with sepsis are required.
With the support of the Australian and New Zealand Intensive Care (ANZIC) Clinical Trials Group and the ANZIC Research Centre, we have commenced an Australian National Health and Medical Research Council (NHMRC)-funded multicentre phase II trial in 2007. The STATInS trial (ACTRN 12607000028404) (www.anzctr.org.au/trial_view.aspx?ID=81692) is a phase II, randomized, placebo-controlled study of the safety, pharmacokinetics, and effect on inflammatory marker levels of atorvastatin in intensive care patients with severe sepsis. This trial is currently underway in more than 14 intensive care units in Australia and New Zealand and we hope the results will provide a platform to plan future trials examining mortality as an endpoint.
References
1 Gao F, Linhartova L, Johnston AM, et al. Statins and sepsis. Br J Anaesth (2008) 100:288–98.
2 Heeschen C, Hamm CW, Laufs U, et al. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation (2002) 105:1446–52.
3 Schouten O, Hoeks SE, Welten GM, et al. Effect of statin withdrawal on frequency of cardiac events after vascular surgery. Am J Cardiol (2007) 100:316–20.[CrossRef][Web of Science][Medline]
4 Blanco M, Nombela F, Castellanos M, et al. Statin treatment withdrawal in ischemic stroke: a controlled randomized study. Neurology (2007) 69:904–10.
5 Kruger P, Fitzsimmons K, Cook D, et al. Statin therapy is associated with fewer deaths in patients with bacteraemia. Intensive Care Med (2006) 32:75–9.[CrossRef][Web of Science][Medline]
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  V. Prinz and M. Endres The Acute (Cerebro)Vascular Effects of Statins Anesth. Analg., August 1, 2009; 109(2): 572 - 584. [Abstract] [Full Text] [PDF]
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