br Medication type Statin br Aspirin br
Medication type Statin
Patient demographics are grouped based on the medication use. Student t-test, Mann-Whitney U test, Fisher exact test, or chi-square test for P-values. Significant P-values are emboldened.
Abbreviations: CA-125, cancer antigen 125; and IQR, interquartile range.
Characteristic No. (%)
VTE risk with statin use (all, P-interactionb0.05).
A key finding of this 3X FLAG Peptide study is that statin use is associated with de-
creased risk of VTE in women with endometrial cancer. Simvastatin
use, in particular, seems to greatly reduce the risk of VTE. Moreover, a
possible synergistic effect of dual statin/aspirin use on VTE risk reduc-
tion may be suggested. This study also suggests that obese women
and those with aggressive tumor characteristics may benefit from statin
independent. Statin use was associated with an approximately 60% re- use to decrease VTE risk.
pirin use did not retain an independent association with decreased VTE strating reduced cancer-related thrombosis with statin use [7–10].
The joint effects of combined statin and aspirin use were examined various cancer types, and endometrial cancer-specific data has been
pirin. Among 219 aspirin users, there were 127 (59.6%) women who tion between statin use and decreased VTE risk in the endometrial can-
used aspirin alone without a statin. On univariable analysis, dual users cer population.
had lower VTE risk compared to those who used a statin or aspirin The findings of this study differ from prior studies that demonstrated
alone (5-year cumulative rates: dual statin and aspirin users 1.2%, statin no association between statin use and cancer-related VTE risk [13,23].
alone 2.9%, aspirin alone 2.6%, and neither of two 7.0%, respectively, P = These studies examined either a different statin type (rosuvastatin) or
0.039). When type of VTE was examined (Table S1), dual users had the a different gynecologic malignancy. Of note, our study also found no as-
lowest incidence of PE among the groups, although this did not reach sociation between rosuvastatin use and VTE. These results suggest that
statistical significance (0% for dual statin and aspirin use, 1.0% for statin effects on VTE risk may vary based on the type of statin used and the
On multivariable analysis adjusting for patient characteristics, Aspirin use did not decrease the risk of VTE in our study. Prior stud-
medical comorbidity, tumor factors, treatment types, and survival ies mainly examined the impact of aspirin on cancer incidence or sur-
events (Table 4), we observed statistically non-significant joint effect vival , and the association of aspirin and VTE has not been
of dual statin and aspirin use on VTE risk compared to non-use (P- addressed in endometrial cancer. Aspirin use seems to protect against
interaction = 0.090). Albeit statistically non-significant findings, dual cancer-related thrombosis in various other cancers including ovarian
statin/aspirin use conferred qualitatively lower VTE risk than statin cancer (one of the most thrombogenic malignancies) [13,14]. More
alone or aspirin alone: adjusted-HR for dual statin/aspirin use 0.27 data would be useful to examine the effects of aspirin on VTE in malig-
While the exact mechanism remains uncertain, a biological plausi-
When stratified by statin type (Table 5), simvastatin demonstrated bility to explain the protective effects of statin and aspirin use against
the highest reduction of VTE risk on multivariable analysis, although it endometrial cancer-related VTE is that both drugs possess anti-
did not quite reach statistical significance (5-year cumulative rates: inflammatory properties . Statins inhibit the interleukin 6-related
The impact of clinical-pathological factors on VTE risk reduction or the prostaglandin E2-mediated inflammatory mechanism [12,25].
with statin use was examined (Table 6). We observed statistically signif- Endometrial cancer in particular often affects obese women, in whom
icant interaction for statin use in terms of body habits, diabetic status, excess adiposity may lead to a pro-inflammatory state . Moreover,
histology type, tumor marker, hysterectomy mode, chemotherapy use, aggressive tumor states also may contribute to increased inflammation.
and disease status on multivariable analysis (all, P-interaction b 0.05).