Trial Information

A Retrospective Analysis of Statin Use and Outcome After Thoracic Cancer Surgery

Statins are well established for the use of primary and secondary prevention of
cardiovascular disease. Moreover, there is increasing evidence that statins have numerous
effects separate from their lipid lowering properties—pleiotropic effects. These pleiotropic
effects, including a reduction in the inflammatory response and improved endothelial
function, may improve perioperative outcomes via modulation of the surgical stress response.
Improved perioperative outcomes have been demonstrated in patients undergoing vascular,
cardiac and non-cardiovascular surgery. Specific to the thoracic surgery population, statin
use has been reported to reduce the incidence of atrial fibrillation.

Statins, via inhibition of the rate limiting step of the mevalonate pathway, have also
sparked interest in their potential anticancer effects as well as in cancer prevention.
There is some evidence for anticancer effects of statins in patients with esophageal and
lung cancer. Additionally, other agents with known anti-inflammatory effects also point to
the potential for improved outcome in cancer patients. In this regard, aspirin use is
reported to associate with prolonged survival in breast cancer patients, while perioperative
use of anti-inflammatory agents (COX-II inhibitor use and lung cancer; aprotinin use and
mesothelioma; aprotinin use and esophageal cancer) is associated with improved postoperative
survival. Moreover, the use of regional analgesia is commonly employed in the thoracic
surgery population and has been associated with attenuation of metastasis and improvement in
recurrence rates for some types of cancers.

In a prospective pilot study of patients undergoing elective thoracic surgery, a
collaborative member of our group recently found that patients suffering postoperative
complications had poorer endothelial function, as measured by flow mediated dilation. Those
patients with poorer endothelial function had greater wound healing complications (6% vs.
0%, p=0.01), longer ICU length of stay (4 vs. 0.9 days, p=0.02), and longer hospital length
of stay (14 vs. 6.9 days, p=0.01). Although this pilot study was underpowered to demonstrate
a significant correlation between Brachial Artery Reactivity Testing (BART) derived
endothelial function and "all" postoperative complications, it provides hypothesis
generating data and supports the hypothesis that statins, as modulators of endothelial
function, may have a role in improving postoperative outcome.