Impact of Chronic Statin Use During Surgery on Inflammation and Infection Rates
Status:
Completed
Trial end date:
2011-07-01
Target enrollment:
Participant gender:
Summary
Despite improvements in perioperative care, non-cardiac surgery remains associated with
significant and costly complications. Analysis of perioperative deaths in the United Kingdom
suggests that roughly 80% are directly attributable to infectious and cardiovascular
complications. The best available evidence suggests that medical optimization is the
preferred strategy to reduce cardiac risks but there has been no novel strategy to reduce
nosocomial infection rates in over 20 years.
Emerging evidence in both the non-operative and operative setting suggest that statin drugs
may prevent both infectious and cardiac events. The mechanism(s) of action are not entirely
clear but appear to independent of lipid lowering effects and are often referred to as
pleiotropic effects. Two key elements of the pleiotropic effects of statins appear to be
their anti-inflammatory properties and improved endothelial vascular reactivity. The statin
dose required to maximize these effects is unknown. A large observational trial suggests a
contradictory dose effect with higher doses associated with reduced infectious complications
and lower doses associated with fewer cardiac complications. Doctors therefore still have
many unanswered questions about the use of statins in the perioperative setting. Should they
be routinely started on all or only certain surgical patients? What dose of statin should be
used? If a patient is already on a statin, should their dose be altered perioperatively? The
latter question is particularly relevant in light of the marked increase in statin use.
Recruitment logs for an ongoing trial demonstrate that over 70% of patients undergoing
high-risk surgery were taking a statin but at markedly variable doses. This population
presents an ideal opportunity to determine if there is a dose response relationship between
statins and pleiotropic effects. We therefore propose an observational study that will
determine anti-inflammatory and endothelial effects in high-risk surgical patients on varying
doses of a perioperative statin drug.
Atorvastatin diminishes the rise in C-reactive protein (CRP), measured 48 hours after
elective vascular surgery, in a dose dependent fashion.
Secondary Hypotheses:
Atorvastatin reduces endothelial dysfunction after elective vascular surgery, as measured by
brachial artery ultrasound, in a dose dependent fashion.