Although the association between AF and cancer has been extensively studied before (5,9-13), the association between AF and AIS/TIA in the setting of cancer, on the contrary, has not. Several studies have investigated the risk factors for developing AIS/TIA in cancer and non-cancer patients and found that classical risk factors and stroke patterns were comparable in both groups of patients. However, up to our knowledge, this is the first study that compared cancer patients who developed AIS/TIA to a control group of cancer patients without AIS/TIA with the same age, gender, type of cancer and were managed at the same facility within the same time frame (18-22).
We hypothesized that since both AF and cancer are independently associated with an increased risk of stroke, this risk should increase in the setting of concurrent AF and cancer. In our study, we retrospectively assessed all consecutive patients who developed ischemic AIS/TIA at our institution over the span of 5 years; and found that among the 136 patients who developed AIS/TIA, 14 % had AF (new onset or at baseline) which significantly and independently correlates to the likelihood to develop AIS/TIA in cancer patients. Similar findings in a large cohort study by Hu et al showed that cancer patients who developed AF, compared to those who did not, had a significantly higher risk of thromboembolism including strokes (9).
The correlation between the CHA₂DS₂-VASc score and stroke risk was previously described by Patell and his colleagues (10). They concluded that in cancer patients with preexisting AF, a higher CHADS2 and CHA₂DS₂-VASc score were both associated with increased risk of ischemic stroke. In our study, we included consecutive cancer patients who developed AIS/TIA regardless of their AF status, cancer type, duration, or stage; and we assessed the utility of CHA₂DS₂-VASc to predict AIS/TIA in all patients even if they didn’t have any evidence of documented AF. Moreover, we included the CHA₂DS₂-VASc score instead of the CHADS₂ score given its increasing importance in the assessment of stroke risk in patients with AF. We hypothesized that since many components of the CHA₂DS₂-VASc score such as heart failure, hypertension, old age, and diabetes mellitus were found to be associated with stroke in the general population (16,17); this score would predict the risk of stroke in cancer patients regardless of the presence of AF. We found that proportions of patients who had AIS/TIA and a high CHA₂DS₂-VASc score (of >=2 in males and >=3 in females) regardless of AF diagnosis are larger than those of their pairs in the control group who did not develop AIS/TIA (71% vs. 52%, p-value < 0.001 with a matched OR (95% CI) of 3.08 (1.61 – 5.91). In addition to the CHA₂DS₂-VASc score, renal disease, dyslipidemia, and being on active cancer treatment significantly predict AIS/TIA in cancer patients. These findings will raise questions regarding the benefit of adding more variables to the CHA₂DS₂-VASc score or the possibility of inventing another scheme that can predict AIS/TIA in cancer patients to apply preventive measures.
In our study, we found that those with a history of previous ischemic stroke or AF have higher odds of developing AIS/TIA independently from many other factors that are attributed to cancer itself. This finding is unique among many studies where atherosclerosis and vascular risk factors remain the most common risk factors of stroke in cancer and non-cancer patients (18,19).
Finally, we found that cancer patients who developed AIS/TIA when compared to patients without AIS/TIA are more likely to die after an AIS/TIA diagnosis. Similar findings were concluded before by several clinical studies (2,23-25) stating that the prognosis may be worse in patients with cancer and stroke, due to reduced general health and the prognosis of cancer itself. This reflects the need for clinicians to be aware of the impact of these events on mortality.
Based on these results, prevention of AIS/TIA in cancer patients should be based on assessing these risk factors. Preventive measures should be considered while accounting for the increased risk of bleeding, as our study found that patients in the AIS/TIA group had a significantly higher HAS-BLED score. To date, a specific approach to prevent AIS/TIA in cancer patients has not yet been established; demanding the need for future studies to prospectively validate these findings and establish a cancer-specific stroke prediction score.
Our study is subject to the same limitations as other retrospective studies involving chart-reviewing due to the nature of the data entered into the electronic medical records which was not pre-designed for clinical research purposes. However, special algorithms and databases were created, and special care was taken in collecting and reviewing the data by our team. Another limitation in our study is the relatively small number of patients, despite the inclusion of all patients who developed AIS/TIA over a period of 5 years. This is attributed to restricting the inclusion of patients only to those subjected to sufficient evaluation which concluded a definitive diagnosis of ischemic AIS/TIA. Furthermore, patients with a vague diagnosis or patients with brain hemorrhage or brain metastasis were excluded.