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Editorials
gle risk factor (cumulative incidence of ATE 1.4-2.7% at 2 years) (Online Supplementary Appendix).8
The risk of cancer-related ATE has been reported to vary during the disease, being highest during the first 6- 12 months after diagnosis and then declining.12-14 In the CATS cohort, the peak of ATE soon after diagnosis was modest and was then subsequently constant over the entire follow-up period, in contrast to VTE, which peaked during the first six months after diagnosis.8 This distribu- tion could be due to different compositions of the patient cohorts as regards type of cancer, as well as the presence of cardiovascular risk factors. The time distribution of cancer-related ATE has been reported to vary according to the nature of the disease. Patients with colorectal cancer, bladder cancer, and non-Hodgkin lymphoma showed an increased risk of myocardial infarction but not of ischemic stroke beyond one year.14 On the other hand, attenuation of the incidence rate of ATE over time or per- sistence up to ten years from the diagnosis has been var- iously described according to different cancer diag- noses.12,13
However, the constant rate of ATE over time could be explained by the role of cardiovascular risk factors as a persistent trigger independently of the course of the can- cer. It should be pointed out that, in the CATS cohort, car- diovascular risk factors that are significantly associated with ATE, such as hypertension or known arterial cardio- vascular disease, are present in 37.5% and 8.5% of the cohort, respectively. Moreover, 303 patients (16.1% of the entire cohort) were at higher risk (i.e. presence of 2 or more cardiovascular risk factors) (Online Supplementary Appendix).8
In cancer patients, the development of ATE has been reported to be associated with a 4-5-fold increased hazard for death.10,14 This was substantially confirmed in the CATS cohort, where the occurrence of ATE was associat- ed with a 3.2-fold increased risk of death.8
The major limitation of the study of Grilz et al.,8 as of the other studies, is the lack of information about cancer treatment (chemotherapy or radiotherapy). Many thera- peutic agents are associated with a significant risk of ATE or VTE, as recently reviewed (Figure 1).16,17 Therefore the drugs used for the active treatment of cancer are essential co-variates in the estimate of the hazard risk of the can- cer-related thrombosis. Moreover, antithrombotic pro- phylaxis administered during active therapy should be taken into account. In the RIETE cohort of cancer patients who have had a VTE event, 86% of the subsequent ATE events occurred during heparin treatment and only 6.3% during antiplatelet treatment.15
In conclusion, ATE is fully recognized as a less frequent but key part of Trousseau syndrome, complicating the course of cancer and having a significant impact on the prognosis. As has been well established for VTE, ATE can be the first signal of an otherwise occult malignancy and can precede the overt diagnosis,4,18 such that it should arouse suspicion of a potential cancer, especially in those patients without cardiovascular risk factors.
The awareness that cancer itself could be an additional risk factor for ATE, and that cancer therapy can also cause
short-term and long-term cardiovascular complications, makes it mandatory to identify high-risk patients, to mod- ify the pre-existent cardiovascular risk factors, and to adopt effective antithrombotic prophylaxis.19,20 Early diagnosis and timely intervention in response to these issues can sig- nificantly improve the management of cancer patients and lead to a better outcome, especially for those who are eld- erly or who have cardiovascular risk factors, and those undergoing therapies with cardiovascular toxicity.
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