Thrombolysis in Ischemic Stroke Without Arterial Occlusion at Presentation
Lahoti and colleagues sought to investigate whether recombinant tissue-type plasminogen activator (r-tPA) is beneficial for patients with acute stroke who present without a visible arterial occlusion as defined by standard computed tomography or magnetic resonance angiography before r-tPA administration. This is an important issue because the main mechanism of action, by which systemic r-tPA is expected to result in improved outcome after stroke, relates to r-tPA–mediated clot dissolution with subsequent vessel recanalization and improved tissue perfusion. Accordingly, r-tPA may not provide significant benefit while exposing the patient to potential complications in the absence of an arterial occlusion. To answer their question, the authors retrospectively analyzed 256 patients treated at large academic centers in the United States, Switzerland, France, and India. Compared with nonthrombolysed subjects, patients who received r-tPA (n=103) were significantly older, had a higher admission National Institutes of Health Stroke Scale score, and more frequently had diabetes mellitus. Despite this imbalance, patients receiving r-tPA had significantly more frequently an excellent 90-day outcome (modified Rankin Scale score of ≤1) than those who were not treated (adjusted odds ratio, 3.8; 95% confidence interval, 2.0–7.0; P<0.01). Similarly, r-tPA treatment was associated with significantly more frequent perfect outcome (modified Rankin Scale score=0) and good outcome (modified Rankin Scale score ≤2), respectively (P<0.01 each). Symptomatic intracerebral hemorrhage rates were higher in treated patients (4.9% versus 0.7%; P=0.04). Nevertheless, poor outcome (modified Rankin Scale score ≥4) was not significantly different between treated and untreated patients (P=0.27). Notably, when analyses were stratified according to lacunar versus nonlacunar stroke subtypes, r-tPA remained significantly associated with an excellent outcome in nonlacunar strokes only. Yet, perfect outcome was more likely with r-tPA in both stroke subtypes (P<0.05). Poor outcomes were similar in treated versus nontreated patients in both stroke subtypes. Although limited by its retrospective design, this study highlights that r-tPA likely provides benefit to eligible patients with acute ischemic stroke even in the absence of a visible arterial occlusion. Further study is warranted to elucidate whether this is related to microvascular recanalization versus r-tPA–mediated effects leading to neuroprotection and recovery and whether results can be replicated in a prospective study. See p 2722.
Distal Single Subcortical Infarction Had a Better Clinical Outcome Compared With Proximal Single Subcortical Infarction
Lacunar infarcts comprise ≈20% to 25% of all ischemic strokes and have heterogeneous underlying pathophysiologies. The most common causes relate to atheromatous branch disease, small vessel atherosclerosis, and lipohyalinosis. These conditions preferentially affect different sites of the microvasculature (proximal in the former 2 and distal in the last). Accordingly, resulting lacunar infarcts may differentially affect outcome. To elucidate this issue, Zhang and colleagues sought to examine differences in vascular risk factors, prevalence of lacunes and leukoaraiosis, as well as clinical outcome in patients with proximal (pSSI) versus distal (dSSI) single subcortical infarction. To this end, they investigated 400 subjects with small arterial occlusion from the prospective, multicenter, hospital-based Chinese IntraCranial AtheroSclerosis (CICAS) Study. Three-tesla MRI was used to define the lacunar lesion location as pSSI (n=208) versus dSSI (n=192), estimate lesion volume, and to grade leukoaraiosis using the Fazekas scoring system. The primary outcome was progressive deterioration (worsening of ≥4 points of the initial National Institutes of Health Stroke Scale score) or recurrence of ischemic stroke in 1 year. Key baseline differences between pSSI and dSSI subgroups were older age, more severe leukoaraiosis, more frequent microbleeds and pre-existing lacunes, smaller acute infarct volumes, less functional deficits, and less frequent r-tPA use in the latter. After adjustment, absent hyperlipidemia, history of stroke, low National Institutes of Health Stroke Scale score (≤3), high Fazekas score (≥3), and pre-existing lacunar infarcts were significantly associated with dSSI. These data underscore the notion that pSSI and dSSI have a differing pathophysiology, namely pSSI is related to larger (atherosclerotic) arterial disease whereas dSSI is suggestive of small (lipohyalinosis related) arterial disease. If confirmed in prospective studies, this may aid risk stratification and one may envision targeted treatment according to the lacune subtype, such as more strict lipid control for pSSI than for dSSI. See p 2613.
Loss of the Mexican American Survival Advantage After Ischemic Stroke
Morgenstern and colleagues sought to investigate whether the effect of the Hispanic Paradox (lower case fatality for several diseases including stroke in Hispanic Americans compared with non-Hispanic whites [NHWs] despite increased risk factors, comorbidities, and worse access to care) was changing over time. Specifically, they sought to assess population-based trends in mortality after stroke using an urban, nonimmigrant community of Mexican Americans (MAs) and NHWs. Log-binomial regression models were constructed to examine trends in 30-day and 1-year mortality. During the study period, MAs (n=1974) were younger and had more diabetes mellitus and hypertension, whereas NHWs (n=2439) had a higher prevalence of atrial fibrillation and smoking and were more likely to be insured. During the study period (2000–2011), the total 30-day case fatality was 12.9% among NHWs and 8.2% among MAs. Total 1-year mortality was 27.0% among NHWs and 20.7% among MAs. Importantly, model-predicted mortality for an average patient declined from 2000 to 2011 among NHWs from 7.6% to 5.6% (30 days, P=0.24) and 20.8% to 15.5% (1 year, P=0.02), respectively. Conversely, among MAs predicted mortality remained stagnant at 5.1% to 5.2% (30 days, P=0.92) and showed a slight decline from 17.4% to 15.3% (1 year, P=0.26). Ethnic differences in 30-day (P=0.014) and 1-year (P=0.06) mortality were apparent in 2000, but not in 2011 (30 days, P=0.63; 1 year, P=0.92). According to predictive modeling, the 1-year stroke mortality advantage seen for MAs versus NHWs would be reversed by 2023, and the advantage seen for MAs versus NHWs in 30-day case fatality would be reversed by 2028. However, as the authors point out, these predictions should be interpreted cautiously because, as we all know, it is difficult to make predictions, especially about the future. Nevertheless, this study highlights that the Hispanic Paradox is no longer relevant for MA stroke. Because this study cannot inform on the underlying factors, further study is critical to understand this phenomenon and optimize patient management. See p 2588.
- © 2014 American Heart Association, Inc.