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Arterial thromboembolism in patients with cancer
agents and platelet aggregation inhibitors were associated with ATE risk. However, previous studies show that a high pill burden, co-morbidities, and provision of care by multiple physicians compromise medication adher- ence;40,41 we assume that all of these are likely to be of rel- evance in patients with cancer. Therefore, we cannot exclude a bias in this analysis due to a possible lack of medication adherence or persistence. Another possible explanation for the association of use of lipid lowering drugs and platelet aggregation inhibitors could be that physicians had correctly identified those patients with a high cardiovascular risk, and consequently had pre- scribed this medication.
Also cancer-specific risk factors such as anti-cancer treatments (e.g. radiotherapy, platinum-containing chemotherapy, treatment with monoclonal antibodies, tyrosine kinase inhibitors) are known to increase the risk of ATE.24,34-36,42 The major limitation of our study is that we were not able to specifically model the time-dependent contribution of selected cancer therapies, such as platinum and VEGF-targeted agents, to risk of ATE, because not all information on treatment regimens was available. Furthermore, patients receiving therapeutic or prophylac- tic anticoagulation were excluded from the study, which might mean that this study population is less representa- tive.
Another main finding of our study was that the occur- rence of ATE during follow up is associated with an increased risk of mortality. Patients who developed ATE had a 3-fold higher risk of mortality. This is consistent with a recent study that reported a 4-fold increased risk of mortality in patients with cancer and ATE.31 Collectively, these results demonstrate that incidental ATE is a major contributor to death in patients with cancer, and that spe- cial medical attention is needed for patients with cancer and arterial thromboembolic complications to improve their prognosis. With regard to fatal ATE, we have to men- tion that the rate of fatal ATE in our study cohort is lower
than in non-cancer patients.43,44 Therefore, we cannot exclude a possible reporting bias because no routine autopsies were performed in patients included in CATS and it is likely that physicians generally tend to attribute death to the underlying malignancy.
Although previous studies had a larger sample size, these data are taken from retrospective analyses, selected cancer entities or from post-hoc analyses of studies that were not designed to investigate ATE in cancer.45-48 To our knowledge, this is the first study in which data on ATE in cancer patients were collected prospectively. To minimize any potential bias, we retrospectively evaluated different sources for ascertainment of the ATE outcome data and a committee adjudicated all events.
In conclusion, this study used subject-level data of a well-characterized cancer cohort to define the epidemiol- ogy of ATE in patients with malignant diseases. ATE in patients with cancer is a less frequent complication than VTE. In certain cancer types, such as lung and kidney can- cer, the risk of ATE is still as high as the risk of VTE. Furthermore, occurrence of ATE in patients with cancer is associated with an increased risk of mortality, calling for future clinical research efforts to better characterize patients with cancer at risk of ATE and reduce the burden of arterial thromboembolic complications.
Acknowledgments
We thank the members of the adjudication committee: Thomas Gremmel (Clinical Division of Angiology, Department of Medicine II, Medical University of Vienna) and Fritz Leutmezer (Department of Neurology, Medical University of Vienna).
Funding
The study was funded by the Anniversary Fund of the Austrian National Bank (“Jubiläumsfonds der Österreichischen Nationalbank (OeNB)” project numbers #10935, #12739 and #14744) and the Austrian Science Fund (FWF), Special Research Program (SFB) 54.
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