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  • br Joint effects of statin and aspirin


    Joint effects of statin and aspirin use on venous thromboembolism risk.
    Adjustment model Demographics alone
    Demographics and
    comorbidity, and tumor comorbidity, tumor factors,
    comorbidity, tumor factors,
    and treatment type
    treatment type, and
    survival events
    Characteristic Adjusted-HR P-value*
    Adjusted-HR P-value*
    Adjusted-HR P-value* Adjusted-HR P-value*
    Adjusted-HR P-value*
    Statin alone
    ASA alone
    Cox proportional hazard regression models for venous thromboembolism risk. *P-values represent interaction. Significant P-values are emboldened. Demographics included age (every quartile), race/ethnicity (Asian versus non-Asian), and obesity (b30.0, 30–34.9, 35.0–39.9, and ≥40.0). Comorbidities included hypertension (yes versus no), L-Glutathione Reduced (yes versus no), and hypercholesterolemia (yes versus no). Tumor factors included histology (type I versus type II), cancer stage (I–II versus III–IV), and CA-125 (b35 versus ≥35 IU/L). Treatment factors included hysterectomy (none, minimally-invasive, and laparotomy) and chemotherapy use (yes versus no). Survival events included endometrial cancer recurrence (yes versus no). Coun-try type was not entered in the model because of concern for multicollinearity for race. Abbreviations: HR, hazard ratio; CI, confidence interval; and ASA, aspirin.
    aspirin may reduce the inflammatory milieu as a whole and reduce the risk of VTE. Indeed, our study found that obese women (representing in-flammatory status in excess adiposity) or type II tumor histology/recur-rent disease (representing inflammatory status from aggressive tumor behavior) benefitted from statin use to reduce VTE risk.
    Another biological mechanism may include the anti-tumor effects of statins and aspirin. In endometrial cancer, VTE is strongly associated with recurrent disease [6]. Agents that might reduce cancer recurrence may indirectly reduce the risk of VTE. Recent clinical data have shown that statins and aspirin may be protective against disease progression in endometrial cancer [15,16]. However, these studies did not examine VTE, and this association remains understudied.
    Our results showed that type of statin also affects VTE incidence in endometrial cancer. Specifically, simvastatin demonstrated the largest reduction of VTE risk compared to other statins (Table 4). Our findings are consistent with a recent large-scale population-based prospective study in that simvastatin significantly reduced VTE risk whereas other higher potency statins did not as shown in a general population [25]. However, possibility for a lack of adequate sample size may be a con-cern. That is, rosuvastatin and fluvastatin uses were suggestive for de-creased VTE risk but it did not quite reach statistical significance in their study. Whether different statin types exert different anti-inflammatory or -tumor effects resulting in altered VTE risk in endome-trial cancer would be of interest and further study is warranted.
    Strengths of this study include the large sample size, allowing vari-ous adjustment models and rigorous analysis to ensure the durability of the association between statin use and VTE risk. Weaknesses of this study include lack of information on the dose and duration of medica-tions, which may suggest a volume-dependent risk reduction [24]. Data on compliance in medication usage or discontinuation of medica-tion during follow-up was not available. A relatively short follow-up time additionally limits the accuracy of capturing VTE events. Side
    Table 5
    Statin type-specific effects on venous thromboembolism.
    effects related to statin and aspirin use were also not available, and a composite endpoint together with risks and benefits was not assessable.