Impact of Chronic Statin Use During Surgery on Inflammation and Infection Rates

• Status: Completed
• Trial end date: 2011-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ottawa Hospital Research Institute
• Treatments: Atorvastatin; Atorvastatin Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Criteria

Inclusion Criteria:

• over 45 years of age

• able to have a baseline brachial ultrasound test before their day of surgery

• elective high-risk surgery defined by use of the POISE criteria

Exclusion Criteria:

• lack of informed consent

• pregnant

• contraindication to the brachial artery ultrasound test protocol (i.e. contraindication to 0.4 mg sublingual nitroglycerin)

• enrolled in another conflicting study

• previously enrolled in STAR-VaS or STAR-VaS2