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six months after diagnosis of cancer and then declines.38 Using flexible parametric modeling, we could demon- strate that in contrast to VTE, the rate of ATE does not appear to have a peak but remained relatively constant over the whole follow-up period. Hence, long-term strate- gies to effectively prevent ATE in cancer patients, and especially in cancer survivors, are needed. Further research has to be conducted to investigate the optimal manage- ment strategies. In this regard, a phase I trial is currently underway evaluating aspirin and statin in patients with cancer to prevent thrombosis (clinicaltrials.gov identifier: 02285738).39 We can speculate whether a primary antithrombotic prevention of ATE would have the great- est net-clinical-benefit in tumor entities with a high absolute ATE risk, such as in patients with lung and renal
cancer, or in patients with individual risk factors for ATE. The link between cancer and ATE could be explained in part by common risk factors, such as higher age and smoking. However, it is unlikely that the ATE burden in cancer patients is completely attributable to these and other general risk factors. In our study, only hypertension and a known arteriosclerotic cardiovascular disease were independently associated with the risk of ATE. We also examined the association of other cardiovascular risk fac- tors and the occurrence of ATE in patients with cancer. Neither the body mass index nor diabetes, dyslipidemia, or prior VTE at study entry were independently associated with the risk of ATE. However, these analyses might be under-powered due to the low absolute number of patients with ATE. In contrast, the use of lipid lowering
Figure 4. Cumulative impact of cardio- vascular risk factors on the risk of arteri- al thromboembolism (ATE). Competing risk analysis was used to analyze the inci- dence of ATE, considering venous throm- boembolism (VTE) and death-from-any- cause as competing risk events. SHR: subdistribution hazard ratio;CVRF: cardio- vascular risk factors.
Figure 5. Landmark analysis of predicted overall survival according to arterial thromboembolism (ATE) status after three months of follow up. 1745 patients survived for at least three months (“land- mark time”), of whom 13 had developed ATE within the first three months and had survived until the landmark time. Four patients had developed ATE within the first three months and died before the landmark time; 31 patients had devel- oped ATE after the landmark time. “Predicted” instead of “observed” overall survival was chosen due to the small numbers of patients who had developed ATE within the first three months (n=13).
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haematologica | 2018; 103(9)