We found that prior treatment with antiplatelet agents was associated with a reduction of stroke severity in patients with cerebral thrombosis who had a prior history of stroke. Antiplatelet agents may limit the size and extent of thromboses, even if patients with stroke experience subsequent thrombotic infarction .
Antiplatelet agents are considered to reduce stroke severity as well as the risk of ischemic stroke [1–6, 9, 11–14], like anticoagulant agents . Several studies, however, have reported negative results [15–23]. The largest report was from the International Stroke Trial, in which previous aspirin use was associated with rather greater stroke severity, although this association was not significant after adjustment for confounding factors . In those negative reports, there were imbalances of demographic data between antiplatelet users and non-users [15, 17, 18, 23]. In comparison with non-users, antiplatelet users tend to be older, and to have more vascular risk factors, including atrial fibrillation and comorbidities [1–3, 12, 15, 17, 18, 23].
According to previous report, patients treated with antiplatelet agents were approximately 2-3 times more likely to have a previous stroke than those without [4, 9, 12, 15, 18, 23]. It has been shown that among antiplatelet users, 41.4% had a previous stroke or TIA, compared with 11.3% in the non-users .
Prior stroke may considerably affect the premorbid disability and severity at the second stroke onset. To avoid this bias, some studies have only included first-ever stroke, but the results have been controversial [1–3, 19, 22]. On the other hand, there have been few investigations in patients with a history of stroke. In terms of secondary stroke prevention, two old studies showed a protective effect of antiplatelet agents on the severity of subsequent stroke in patients with a history of TIA [5, 6]. In another study, pretreatment with antiplatelet agents reduce stroke severity in those with no history of stroke or TIA, but not in those with a prior history of stroke or TIA . In those studies, however, analysis of patients with a prior history of only stroke was not provided.
There has also been an imbalance in stroke subtypes between those with and without antiplatelet treatment. In previous reports, cardioembolism, which is the most severe subtype of ischemic stroke, was significantly more frequent in stroke patients with prior antiplatelet treatment than in those without [1–4, 12, 15, 18]. It has been well established that anticoagulant agents are superior to antiplatelet agents in the prevention of cardioembolism, while antiplatelet agents are recommended for non-cardioembolic stroke such as LAA, SVO, and BAD. Because platelets are the main culprit in arterial thrombus formation, antiplatelet treatment is expected to limit thrombus size due to suppression of increased platelet activation . Some researchers have reported that the effect of antiplatelet agents on stroke severity was most remarkable in patients with LAA [1, 12] and in patients without potential cardiac sources of embolism, such as atrial fibrillation and prosthetic heart valve .
To overcome an imbalance of clinical background between those with and without antiplatelet treatment, some researchers have used multivariate analysis [2, 13, 23], particularly in using propensity score matching [3, 12]. Again, there has been no previous study that targeted patients with a prior history of stroke, i.e., secondary stroke prevention. So, we focused on secondary stroke prevention by including only patients with a history of stroke and excluding patients with cardioembolism or prior use of anticoagulant agents. Narrowing the inclusion to patients with a history of stroke and cerebral thrombosis may eliminate any significant imbalance, except dyslipidemia, between those with and without prior antiplatelet use, and it may enhance the effect of prior use of antiplatelet agents at the time of a second stroke.
There are several limitations to this study. First, this study was a single center cohort with a small number of patients, and was a retrospective observational study. The results should be confirmed by a large, multi-center, prospective study. Second, a previous stroke may include hemorrhagic stroke. Only a prospective study could evaluate bleeding risk. Third, the duration from symptom onset to admission was long, because some types of stroke could be getting worse for hours or days from onset, even in patients treated with antiplatelet agents. Fourth, there was no data regarding drug resistance, which might occur in some patients with a recurrent cerebral thrombosis. Aspirin and clopidgrel resistance should be considered in future studies. Despite these limitations, the results of this study are clinically important in the current stroke practice.