Advertisement

Topics

Statin Drugs to Prevent Complications During Surgery

2014-08-27 03:19:43 | BioPortfolio

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).

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.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Conditions

Inflammation

Intervention

Atorvastatin, Atorvastatin, Placebo

Location

The Ottawa Hospital
Ottawa
Ontario
Canada
K1Y4E9

Status

Active, not recruiting

Source

Ottawa Hospital Research Institute

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:19:43-0400

Clinical Trials [1068 Associated Clinical Trials listed on BioPortfolio]

A Study of Torcetrapib/Atorvastatin vs Atorvastatin Alone or Placebo in Patients With High Cholesterol

The Torcetrapib project was terminated on December 2, 2006 due to safety findings. A study to look at lipid levels in subjects taking the study drug, Atorvastatin alone or placebo.

Bioequivalence Study Comparing A New 80 Mg Atorvastatin Tablet To A 80 Mg Atorvastatin Commercial Tablet

To determine whether new 80 mg atorvastatin tablets are bioequivalent to 80 mg commercial atorvastatin tablets (Lipitor®).

Investigations on Differences in Atorvastatin Metabolites Ratios as a Diagnostic Tool in Detecting Atorvastatin Induced Myotoxicity

The primary objective of the study is to investigate the ratios of p-hydroxyatorvastatin to atorvastatin in patients receiving atorvastatin treatment, who experience muscle adverse events,...

To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg.

The purpose of this study is to evaluate and compare the efficacy and safety of ezetimibe plus atorvastatin versus atorvastatin in hypercholesterolemic patients at moderately high risk for...

A Study Of The Efficacy Of Atorvastatin In Lowering Cholesterol In Latin American Patients With High Cholesterol

The purpose of this study is to determine the percentage of patients who would reach a cholesterol goal after atorvastatin treatment.

PubMed Articles [4925 Associated PubMed Articles listed on BioPortfolio]

Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress.

Vascular inflammatory responses play an important role in several cardiovascular diseases. Of the many pro-inflammatory vasoactive factors implicated in this process, is aldosterone, an important medi...

A combination of indomethacin and atorvastatin ameliorates cognitive and pathological deterioration in PrP-hAβPPswe/PS1 transgenic mice.

Mounting evidence has shown that inflammation might drive Alzheimer's disease (AD) pathology and contribute to its exacerbation. Previous studies have indicated that indomethacin or atorvastatin are b...

Application of the method of liquid chromato-mass spectrometry for determination of bisoprolol and atorvastatin.

A technique has been developed for the quantitative determination of bisoprolol and atorvastatin in mixed saliva on a LCMS-8040 triple quadrupole liquid chromatographic mass spectrometer with ionizati...

Atorvastatin prevents Lipopolysaccharide-Induced Depressive-Like Behaviour in Mice.

Clinical and pre-clinical evidences indicate an association between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. At...

Re: Timu J. Murtola, Hemo Syvälä, Teemu Tolonen, et al. Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy-A Randomized, Double-blind, Placebo-controlled Clinical Trial. Eur Urol 2018;74:697-701.

Medical and Biotech [MESH] Definitions

A pyrrole and heptanoic acid derivative,HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITOR (statin), and ANTICHOLESTEREMIC AGENT that is used to reduce serum levels of LDL-CHOLESTEROL; APOLIPOPROTEIN B; AND TRIGLYCERIDES and to increase serum levels of HDL-CHOLESTEROL in the treatment of HYPERLIPIDEMIAS and prevention of CARDIOVASCULAR DISEASES in patients with multiple risk factors.

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.

Inflammation of the PERIAPICAL TISSUE. It includes general, unspecified, or acute nonsuppurative inflammation. Chronic nonsuppurative inflammation is PERIAPICAL GRANULOMA. Suppurative inflammation is PERIAPICAL ABSCESS.

Inflammation of the lung parenchyma that is associated with PLEURISY, inflammation of the PLEURA.

More From BioPortfolio on "Statin Drugs to Prevent Complications During Surgery"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Anesthesiology
An anesthesiologist (US English) or anaesthetist (British English) is a physician trained in anesthesia and perioperative medicine. Anesthesiologists are physicians who provide medical care to patients in a wide variety of (usually acute) situations. ...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...


Searches Linking to this Trial