Recurrent Stroke Risk in Patients With 50-99% Carotid Stenosis
Recurrent Stroke Risk in Patients With 50-99% Carotid Stenosis
The main findings of this study were that the risk of recurrent ipsilateral ischemic stroke was similar regardless of additional ipsilateral events within 7 days before and/or after the presenting event and that the majority of recurrent strokes occurred in patients without additional events (i.e. in clinically stable patients).
At least in our clinical practice, a patient with additional events is perceived as being at high risk for a recurrent stroke. Therefore, additional events initiate an extraordinary effort with expedient preoperative evaluation and early CEA - hence, the shorter delay to CEA for patients with additional events in this study. During the time period of this study, this meant the patient was transferred the next office day and stayed until the operation. Those measures are currently standard practice; whereas, extraordinary measures are now transfers and operations during evenings and weekends.
One additional event within 7 days before the presenting event had a tendency to incur an increased risk of recurrent stroke, especially among patients with TIA as the presenting event. There are several study limitations to consider when interpreting this finding: (1) Although the patients were prospectively included, the data for events the days before the presenting event were ascertained retrospectively. (2) Patients with additional events underwent CEA early because this reduced the observation time in this group. (3) The most important limitation is the moderate statistical power (230 patients and 33 outcome events), especially when interpreting negative subgroup findings. Given these limitations, it could be a false negative finding that we could not detect any difference in risk between those with and without additional events. However, there was no dose–response relationship (patients with ≥2 additional events seemed to have a lower risk) and no consistency (one additional event after the presenting event tended to be a protective factor rather than a risk factor), which indicate it was not a false negative finding. The lack of dose–response relationship was supported by the finding that patients with several additional events (≥3 within 7 days or ≥10 within 90 days) seemed to continue to have additional transient events, but did not have an increased risk of stroke.
In previous studies of patients with TIAs of mixed etiologies, one or more recurrent event within 7 days before the presenting event was associated with symptomatic 50–99% carotid stenosis and lead to an increased risk of stroke. It is possible that, among patients with TIAs of mixed etiologies, additional events act as risk factors by indicating a high risk etiology (i.e. symptomatic 50–99% carotid stenosis). However, among the patients with this high risk etiology, additional events at presentation are not a risk factor for stroke. This contention has already been reported for large-artery atherosclerosis in a study with 388 patients with TIAs of mixed etiologies. They found large-artery atherosclerosis was the etiology with the highest risk and additional events at presentation were more common (p < 0.001) among patients with large-artery atherosclerosis (42%) than patients with cardioembolism (17%), small vessel disease (13%), other causes (6%), and undetermined causes (24%). Among patients with large-artery atherosclerosis, 16% of patients with additional events at presentation suffered a stroke during the 90 days follow-up, compared to 23% of patients without additional events at presentation (p = 0.49). Although an increased risk for patients with additional events cannot be ruled out based on our results, it is clear that patients without additional events have a high risk of stroke recurrence and most of the recurrent stroke occurred in this group. Thus, it was common that patients sought health care for the first event and suffered a stroke within 7 days, without a transient event in between.
There are two separate clinical implications for the findings in this study. (1) The risk of recurrent ipsilateral ischemic stroke was not increased for patients with additional events. This might be a false negative finding and should be confirmed in further studies; although, the clinical implication is that the risk of ipsilateral ischemic stroke in the acute phase might not be sufficiently high to warrant an emergent CEA, which has a very high risk of perioperative events (11–20%) among patients with unstable symptoms. Thus, it is possible that initial conservative treatment and delayed CEA (perhaps >48 hours since the last event) are more beneficial for these patients. (2) The risk of recurrent ipsilateral ischemic stroke was high among the patients without additional events and most recurrent strokes occurred in this group. Therefore, these patients should undergo an expedient preoperative evaluation for an early CEA. Thus, there is a need to extend expedient management, which might be reserved for patients with additional events, to patients without additional events – i.e. to all patients.
Discussion
The main findings of this study were that the risk of recurrent ipsilateral ischemic stroke was similar regardless of additional ipsilateral events within 7 days before and/or after the presenting event and that the majority of recurrent strokes occurred in patients without additional events (i.e. in clinically stable patients).
At least in our clinical practice, a patient with additional events is perceived as being at high risk for a recurrent stroke. Therefore, additional events initiate an extraordinary effort with expedient preoperative evaluation and early CEA - hence, the shorter delay to CEA for patients with additional events in this study. During the time period of this study, this meant the patient was transferred the next office day and stayed until the operation. Those measures are currently standard practice; whereas, extraordinary measures are now transfers and operations during evenings and weekends.
One additional event within 7 days before the presenting event had a tendency to incur an increased risk of recurrent stroke, especially among patients with TIA as the presenting event. There are several study limitations to consider when interpreting this finding: (1) Although the patients were prospectively included, the data for events the days before the presenting event were ascertained retrospectively. (2) Patients with additional events underwent CEA early because this reduced the observation time in this group. (3) The most important limitation is the moderate statistical power (230 patients and 33 outcome events), especially when interpreting negative subgroup findings. Given these limitations, it could be a false negative finding that we could not detect any difference in risk between those with and without additional events. However, there was no dose–response relationship (patients with ≥2 additional events seemed to have a lower risk) and no consistency (one additional event after the presenting event tended to be a protective factor rather than a risk factor), which indicate it was not a false negative finding. The lack of dose–response relationship was supported by the finding that patients with several additional events (≥3 within 7 days or ≥10 within 90 days) seemed to continue to have additional transient events, but did not have an increased risk of stroke.
In previous studies of patients with TIAs of mixed etiologies, one or more recurrent event within 7 days before the presenting event was associated with symptomatic 50–99% carotid stenosis and lead to an increased risk of stroke. It is possible that, among patients with TIAs of mixed etiologies, additional events act as risk factors by indicating a high risk etiology (i.e. symptomatic 50–99% carotid stenosis). However, among the patients with this high risk etiology, additional events at presentation are not a risk factor for stroke. This contention has already been reported for large-artery atherosclerosis in a study with 388 patients with TIAs of mixed etiologies. They found large-artery atherosclerosis was the etiology with the highest risk and additional events at presentation were more common (p < 0.001) among patients with large-artery atherosclerosis (42%) than patients with cardioembolism (17%), small vessel disease (13%), other causes (6%), and undetermined causes (24%). Among patients with large-artery atherosclerosis, 16% of patients with additional events at presentation suffered a stroke during the 90 days follow-up, compared to 23% of patients without additional events at presentation (p = 0.49). Although an increased risk for patients with additional events cannot be ruled out based on our results, it is clear that patients without additional events have a high risk of stroke recurrence and most of the recurrent stroke occurred in this group. Thus, it was common that patients sought health care for the first event and suffered a stroke within 7 days, without a transient event in between.
There are two separate clinical implications for the findings in this study. (1) The risk of recurrent ipsilateral ischemic stroke was not increased for patients with additional events. This might be a false negative finding and should be confirmed in further studies; although, the clinical implication is that the risk of ipsilateral ischemic stroke in the acute phase might not be sufficiently high to warrant an emergent CEA, which has a very high risk of perioperative events (11–20%) among patients with unstable symptoms. Thus, it is possible that initial conservative treatment and delayed CEA (perhaps >48 hours since the last event) are more beneficial for these patients. (2) The risk of recurrent ipsilateral ischemic stroke was high among the patients without additional events and most recurrent strokes occurred in this group. Therefore, these patients should undergo an expedient preoperative evaluation for an early CEA. Thus, there is a need to extend expedient management, which might be reserved for patients with additional events, to patients without additional events – i.e. to all patients.