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Background: Two recent cerebrovascular studies, Clopidogrel (Clo) in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT), have purportedly demonstrated the superiority of early dual antiplatelet therapy (DAPT), using aspirin (ASA) plus Clo, in comparison to ASA alone following the occurrence of acute minor cerebral infarction or transient ischemic attack. However, limitations to these trials exist that may not have been adequately explored and presented in the literature, and which may impact the overall efficacy and benefit of DAPT in these situations. Herein we provide a detailed and extensive critique of these 2 trials and of a combined analysis, with particular attention to study data and analyses pertaining to hemorrhagic complications., Summary: DAPT may be superior to ASA alone in preventing recurrent cerebral ischemic events, but exclusively during the first 7-10 days of treatment, and probably only in the presence of acute infarction on cerebral imaging. The impact of minor hemorrhages, which are often clinically consequential and which frequently lead to permanent DAPT discontinuation, has not been adequately considered in the available analyses. Based on data from the trials, DAPT use causes more major and minor hemorrhages than ASA use alone or Clo alone, and Clo use results in fewer hemorrhages than the use of ASA alone. Analyses that include hemorrhage data from the period of Clo alone use as part of the DAPT data may provide inaccurate and erroneous conclusions regarding the relative safety and overall net benefit of DAPT use over ASA alone., (© 2020 S. Karger AG, Basel.)

Background: Oral anticoagulants have been associated with greater hematoma expansion in patients with intracerebral hemorrhage (ICH). The purpose of this study was to determine whether the reported use of antiplatelet agents also results in greater hematoma expansion., Methods: Retrospective review of patients with spontaneous supratentorial ICH diagnosed within 6 h of onset, who underwent follow-up head CT approximately 48 h later. Digital imaging analysis of initial and second CT scans was performed for comparison of hematoma volume changes between patients reporting and those not reporting antecedent antiplatelet use. Statistical analyses to determine predictors of ICH volume change and in-hospital mortality were also performed via multivariate regression models., Results: Of the 70 patients included, 17 were documented as taking antiplatelet agents. Groups were comparable regarding baseline demographic, clinical and laboratory characteristics, and the timing of CT scans was similar. Patients reporting antiplatelet use experienced greater absolute increase (7.7 ml vs. 5.5 ml) and proportional increase (110% vs. 21%) in ICH volume than those not reporting antiplatelet use, but these differences were not statistically significant (P = 0.94 and 0.61 respectively; Wilcoxon test). Baseline hematoma volume tended to correlate with percentage volume increase (P < 0.1), whereas IVH was inversely associated with percent volume increase (P < 0.05). Age (P < 0.05), absolute volume increase (P < 0.005), and final volume (P < 0.001) were associated with in-hospital mortality, the rates of which were similar between the two study groups (18% vs. 17%)., Conclusions: Patients reporting antiplatelet use experienced similar degrees of hematoma expansion compared to patients not reporting antiplatelet use.

Combination antiplatelet agents with multiple mechanisms of action are being used with increasing frequency for vascular disorders, including cerebrovascular disease. Limited data exist regarding the efficacy of combination antiplatelet therapy in the primary or secondary prevention of cerebral ischemia, and combination therapies are often used without adequate evidence of efficacy. However, over the last few years, several cerebrovascular and cardiovascular trials have provided some preliminary information on the effectiveness of various combination therapies in preventing cerebral ischemic disease. This article reviews recently completed cerebrovascular and cardiovascular trials that tested a combination antiplatelet regimen against aspirin alone, and that assessed cerebral ischemia as an outcome measure. Controversies pertaining to these trials and to the use of the various combination antiplatelet regimens are discussed. Based on cardiovascular studies, clopidogrel in combination with aspirin has not been proven superior to aspirin alone for the primary prevention of cerebral ischemia. No data exists regarding the combination of clopidogrel and aspirin for the secondary prevention of cerebrovascular disease. The combination of aspirin plus extended-release dipyridamole (xrDP) appears to be superior to aspirin alone in the secondary prevention of cerebral ischemia, but may compromise cardiovascular protection in patients with coexisting coronary artery disease. Combination therapy with aspirin and clopidogrel seems to increase the risk of major hemorrhages, whereas aspirin plus xrDP does not. Ongoing trials are expected to clarify the role of various combination antiplatelet regimens.