Clopidogrel Plus Aspirin Versus Warfarin in Patients With Stroke and Aortic Arch Plaques
Aortic arch atherosclerosis has been associated with increased risk for ischemic stroke and other vascular events (previously reported to be as high as 26% per year), but optimal medical management remains unclear. Amarenco et al sought to test the hypothesis that double antiplatelet therapy with aspirin and clopidogrel confers better protection from new vascular events compared with anticoagulation with warfarin. To this end, they conducted the multicenter Aortic arch Related Cerebral Hazard (ARCH) trial in Australia and France. Patients with an atherosclerotic plaque in the thoracic aorta as defined by transesophageal echocardiography (wall thickness ≥4 mm or wall thickness <4 mm with mobile component proximal the symptomatic artery) and without known other embolic source who presented within 6 months from a nondisabling ischemic stroke, transient ischemic attack, or peripheral embolism were enrolled. The primary end point was a composite of incident ischemic stroke, myocardial infarction, peripheral embolism, vascular death, or hemorrhagic stroke. Three hundred forty-nine patients were randomized over an 8-year period. At this point, the steering committee stopped the trial because no further funding was available. Overall, 33 primary end points (99% ischemic stroke or transient ischemic attack) had occurred during a mean follow-up of 3.4 years. The primary outcome event occurred in 7.6% (aspirin+clopidogrel) versus 11.3% (warfarin) patients (P=0.5). Although vascular death was more common in warfarin-treated patients, total death was similar between treatment arms (4.7% in the aspirin+clopidogrel versus 8.4% in warfarin; adjusted P=0.3). Although the trial did not clarify whether antiplatelet therapy should be favored over anticoagulation in aortic arch disease, the study highlights that appropriate secondary prevention measures substantially lower the risk for vascular events in affected patients. See p 1248.
Cerebral Perfusion and Blood Pressure Do Not Affect Perihematoma Edema
Growth in Acute Intracerebral Hemorrhage
Optimal blood pressure management in the wake of an intracerebral hemorrhage (ICH) has not been established. For example, aggressive blood pressure lowering could reduce hematoma expansion but at the possible expense of jeopardizing cerebral perfusion. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) indicated that perihematoma cerebral blood flow was reduced in ICH. Based on this observation, McCourt et al analyzed ICH ADAPT data to investigate the relationship between perihematoma edema growth, systolic blood pressure, and cerebral blood flow (as assessed by computed tomographic perfusion at 2 hours after baseline computed tomography). The authors defined 5 regions of interest: (1) ipsilesional and (2) contralesional hemisphere, (3) ipsilesional and (4) corresponding contralesional 1-cm rim adjacent to the ICH (1-cm regions of interest [ROI]), as well as (5) edematous tissue surrounding the ICH (no corresponding contralesional ROI was defined). Cerebral blood flow and cerebral blood volume were lower in the edematous ROI compared with the ipsilesional and contralesional 1-cm ROIs, respectively. However, the cerebral blood flow remained well above accepted thresholds for critical tissue ischemia. Expectedly, the relative edema volume (edema volume/hematoma volume) increased from baseline to 24 hours. However, there was no difference in edema volume or edema growth between patients randomized to lower (<150 mm Hg) versus higher (<180 mm Hg) systolic blood pressure targets. There was no significant association between hematoma volume or expansion and aggressive blood pressure management (initiation of therapy within ≈7 hours from onset). Furthermore, there was no significant association between edema growth and cerebral perfusion metrics or blood pressure measures. Last, edema growth was not predicted by hematoma expansion or acute hematoma volume. This study highlights that aggressive blood pressure management does not seem to affect edema formation adversely, which argues against the hypothesis that perihematoma edema forms secondary to focal hypoperfusion. See p 1292.
Effects of Extracranial–Intracranial Bypass for Patients With Hemorrhagic Moyamoya Disease: Results of the Japan Adult Moyamoya Trial
Moyamoya is a progressive congenital or acquired cerebrovascular disorder characterized by focal internal carotid artery stenosis/occlusion and compensatory formation of a collateral network. Hemorrhage may occur because of long-term hemodynamic stress to these wispy, tangled collateral vessels. Accordingly, reduction of hemodynamic stress through bypass surgery could potentially reduce this risk, a hypothesis tested in the Japanese Adult Moyamoya (JAM) trial. Originally designed for a sample size of 160 (80 patients per group), this number was later reduced to 80 because of lower than expected patient recruitment. At 22 institutes with sufficient surgical experience, patients (mean age ≈42 years) were randomized to conservative medical care (nonsurgical group, n=38) versus medical care plus extracranial–intracranial bypass (surgical group, n=42) and accounting for anterior versus posterior circulation hemorrhage. Direct anastomotic bypass surgery was required per study protocol, but additional indirect procedures were allowed. The use of anticoagulants or antiplatelet drugs was not allowed unless the patient had significant cerebral ischemic events. Primary study end points were symptomatic recurrent bleeding, stroke causing significant morbidity (modified Rankin Scale score ≥3), modified Rankin Scale ≥3 from other medical cause, or requirement for extracranial–intracranial bypass in nonsurgical patients. After a mean follow-up of 4.3 years, the primary end point was observed in 13 (34.2%) patients in the nonsurgical group and 6 (14.3%) patients in the surgical group. The hazard ratios of the surgical group compared with the nonsurgical group were 0.391 (95% confidence interval: 0.148–1.029; P=0.057), and the surgical group was at significantly lower risk than the nonsurgical group for the primary end point (3.2%/y versus 8.2%/y; P=0.048; log-rank test). However, details on functional deficits were not provided, and it thus remains to be shown whether surgery truly translates to (long-term) functional benefits. Nevertheless, although statistically marginal, these study results highlight that surgery in the hand of experienced operators can reduce hemorrhagic complications compared with best medical therapy alone. See p 1415.
- © 2014 American Heart Association, Inc.