Statin Drugs to Prevent Complications During Surgery
Information source: Ottawa Hospital Research Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Inflammation; Myocardial Infarction; Myocardial Ischemia
Intervention: Atorvastatin (Drug); Atorvastatin (Drug); Placebo (Drug)
Phase: N/A
Status: Active, not recruiting
Sponsored by: Ottawa Hospital Research Institute Official(s) and/or principal investigator(s): David T Neilipovitz, MD, Principal Investigator, Affiliation: The Ottawa Hospital Greg L Bryson, MD, Principal Investigator, Affiliation: The Ottawa Hospital
Summary
Patients undergoing non-cardiac surgery frequently experience perioperative cardiac
complications that may be due to excess inflammatory reactions. Lipid lowering drugs called
HMG-CoA reductase inhibitors or statins, have anti-inflammatory effects. Although favourable
evidence suggests these drugs could also prevent perioperative cardiac complications,
definitive evidence of anti-inflammatory effects and benefit is lacking. The purpose of this
study to measure the impact of a atorvastatin on patients undergoing surgery. It will
attempt to determine the speed of drug effect as measured by the impact the drug has on the
levels of the inflammatory mediator called C-reactive protein after surgery. It is
hypothesized that the perioperative use of atorvastatin will safely reduce the postoperative
rise in CRP levels at 48 hours after elective vascular surgery. This effect, would then
translate into a reduction of adverse perioperative complications including reduction in
postoperative myocardial ischemia episodes (as measured through Holter monitoring).
Clinical Details
Official title: Short Term Atorvastatin Regime for Vasculopathic Surgical (STAR-VaS) Patients Study
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: C-reactive protein levels at 48 hours postoperatively
Secondary outcome: perioperative myocardial ischemia as detected by Holter monitoringperioperative myocardial injury as measured by troponin levels liver enzyme levels myopathy as assessed by CK levels
Detailed description:
Despite modern improvements in operative care, non-cardiac surgery is still associated with
significant and costly cardiac complications. The incidence of major perioperative cardiac
events varies, ranging from 1% in unselected populations to 15% or more in vascular surgical
patients. An estimated 2 million North Americans yearly experience a perioperative cardiac
event with an associated mortality of 30-50% and financial burden of over 20 billion
dollars. Best evidence suggests that medical optimization is the preferred strategy to
reduce the risks. There exists favorable physiologic evidence and promising clinical
observations that statin drugs may prevent perioperative complications. We propose a
randomized controlled trial to evaluate short-term atorvastatin versus placebo on
inflammatory changes and myocardial ischemia in patients undergoing high-risk non-cardiac
surgery.
The traditional belief on the etiology of perioperative myocardial events has been that
supply-demand discrepancies due to hypotension or hypoxia compromise cardiac oxygen delivery
thus resulting in myocardial ischemia and infarction are in dispute. Therapies that target
supply-demand imbalance, including perioperative beta-blockers, have been disappointing.
Emerging evidence now suggests that most perioperative cardiac events are similar to
non-operative events where rupture of coronary plaques and thrombosis are central to the
development of acute coronary events. Key elements to plaque rupture are inflammation and
endothelial dysfunction. Elevated inflammatory markers, particularly C-reactive protein is
associated with adverse cardiac events. Drugs known as statins offer benefits beyond their
traditional improvement of lipid levels. Statins have so-called pleiotropic effects that
include anti-inflammatory, endothelial function changes and plaque stabilization.
Atorvastatin, a statin with a good safety profile, is particularly effective at improving
inflammatory levels and decreasing cardiac events including death.
Perioperatively, elevated C-reactive protein levels after surgery are associated with
perioperative complications including cardiac events. Thus, strategies to control
perioperative inflammation may reduce complications. Retrospective studies and small
prospective studies suggest that statins would reduce perioperative complications but
definitive evidence is lacking. Questions regarding dose and timing of dosing is unclear.
Likewise, little is proven on the potential pathophysiology of atorvastatin on reducing
perioperative myocardial events. Our hypothesis is that atorvastatin use will reduce the
postoperative rise in CRP levels at 48 hours.
Eligible non-cardiac surgical patients will be randomized into 3 groups with 3 stages of
treatment; namely stage 1 (preoperative period up to 7 days), stage 2 (immediate
preoperative), and stage 3 (first 7 postoperative days). Group A will receive atorvastatin
in all 3 stages. Group B receives placebo in stage 1 but atorvastatin stages 2 and 3. Group
C receives placebo in all 3 stages. Atorvastatin dose in all cases will be 80 mg. C-reactive
protein and lipid levels assess statin effects. Safety is assessed by liver enzymes and CK
levels. Myocardial events assessed by troponin T, ECG and Holter monitoring. Follow-up at 6
months will be done.
Eligibility
Minimum age: 45 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- elective high-risk surgery defined by use of the POISE criteria
- over 45 years of age
Exclusion Criteria:
- lack of informed consent
- contraindication to statin (i. e. liver insufficiency or cirrhosis, active muscular
disorder or myopathy, or previous adverse reaction to statin)
- pregnant
- enrolled in another conflicting study
- previously enrolled in STAR VaS
- presently using a statin drug
Locations and Contacts
The Ottawa Hospital, Ottawa, Ontario K1Y4E9, Canada
Additional Information
Starting date: December 2007
Last updated: October 24, 2011
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