Publications by authors named "Lesly A Pearce"

61 Publications

Aspirin Use and Risk of Subdural Hematoma: Updated Meta-Analysis of Randomized Trials.

J Stroke Cerebrovasc Dis 2021 Aug 13;30(8):105911. Epub 2021 Jun 13.

Department of Medicine (Neurology), McMaster University, Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Background And Purpose: Subdural hematomas are an uncommon, but a serious, bleeding complication of antithrombotic therapies. We update our previous inconclusive meta-analysis to better estimate the risk of subdural hematoma associated with aspirin use.

Methods: For the initial meta-analysis, nine randomized trials published between1980 and 2012 comparing aspirin with placebo/control were considered. Additional data from four large primary prevention trials were added. Two reviewers independently extracted data on subdural hematomas, with differences resolved by joint review and consensus.

Results: Numbers of subdural hematoma were available from thirteen randomized trials involving 155,554 participants comparing aspirin (dosage range 25 mg twice daily to 325 mg daily) to placebo (ten double-blind trials) or no aspirin (three trials). Participants included healthy healthcare providers, older people with vascular risk factors without manifest vascular disease, and those with atrial fibrillation or chronic angina. Pooling all trials, subdural hematomas were identified in 93 of 77,698 participants assigned to aspirin versus 62 of 77,856 participants assigned to placebo/no aspirin. By meta-analysis, the relative risk ratio of subdural hematoma associated with assignment to aspirin was 1.5 (95%CI 1.1, 2.0, p = 0.01; p = 0.9 for heterogeneity, I index = 0%). Based on recent primary prevention trials, subdural hematoma diagnosis averaged 1 per 3,125 people per year without aspirin use; the absolute increase associated with aspirin use was estimated as one additional subdural hematoma per 6,500 patients annually.

Conclusions: This meta-analysis confirms that aspirin use increases the relative risk of subdural hematoma, but the absolute increased rate associated with aspirin therapy is very low for most people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105911DOI Listing
August 2021

Intracranial and systemic atherosclerosis in the NAVIGATE ESUS trial: Recurrent stroke risk and response to antithrombotic therapy.

J Stroke Cerebrovasc Dis 2020 Aug 8;29(8):104936. Epub 2020 Jun 8.

Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Background: Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.

Methods: Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed.

Results: Among 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (p=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5).

Conclusions: East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104936DOI Listing
August 2020

High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source.

Stroke 2020 08 9;51(8):2386-2394. Epub 2020 Jul 9.

Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Germany (J.F.S., C.H.N., M.E.).

Background And Purpose: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS.

Methods: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke.

Results: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41-1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25-0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification (=0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment (=0.3).

Conclusions: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.029628DOI Listing
August 2020

Antithrombotic treatment in patients with stroke and supracardiac atherosclerosis.

Neurology 2020 08 6;95(5):e499-e507. Epub 2020 Jul 6.

From the Department of Internal Medicine (D.S., I.L., K.M., G.N.), Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; School of Biomedical Engineering and Imaging Sciences (G.G.), King's College, London, UK; Department of Biostatistics and Research Support (K.P.), Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; biostatistics consultant (L.A.P.), Minot, ND; Department of Clinical Therapeutics (E.K., K.V.), Alexandra Hospital, University of Athens, Greece; Imperial College London (E.K.), UK; and Department of Internal Medicine, School of Medicine (H.M.), University of Ioannina, Greece.

Objective: To compare the efficacy and safety of oral anticoagulants vs antiplatelets in patients with stroke and atherosclerotic plaques in the aortic arch or cervical or intracranial arteries, collectively described as supracardiac atherosclerosis.

Methods: We searched PubMed and Scopus until August 28, 2019, for randomized trials comparing oral anticoagulants vs antiplatelets in patients with stroke and supracardiac atherosclerosis using the terms "anticoagulant or anticoagulation" and "antiplatelet or aspirin" and "randomized controlled trial or RCT" and "stroke or cerebral ischemia" and "aortic or carotid or vertebrobasilar or intracranial or atherosclerosis or stenosis or arterial." Four outcomes were assessed: recurrent ischemic stroke, major ischemic event or death, major bleeding, and intracranial bleeding. Treatment effects (relative risk [RR] and 95% confidence interval [CI]) were estimated by meta-analysis using random-effects models.

Results: Among 1,117 articles identified in the literature search, results from 10 randomized controlled trials involving 6,068 patients with stroke/TIA with supracardiac atherosclerosis were included in the meta-analysis. Recurrent ischemic stroke rates were 2.94 per 100 patient-years in the anticoagulant-assigned patients vs 3.30 per 100 patient-years in the antiplatelet-assigned patients (RR, 0.91; 95% CI, 0.70-1.18 for the SJ estimator, I = 26%). Major ischemic event or death rates were 4.39 per 100 patient-years in anticoagulant-assigned patients vs 4.32 in antiplatelet-assigned patients (RR, 1.03; 95% CI, 0.79-1.35; I = 54.5%). Major bleeding rates were 2.88 per 100 patient-years in anticoagulant-assigned patients vs 0.82 in antiplatelet-assigned patients (RR, 3.21; 95% CI, 1.96-5.24; I = 46%).

Conclusion: This systematic review and meta-analysis showed that anticoagulant-assigned patients with stroke and supracardiac atherosclerosis were not at different risk of ischemic stroke recurrence and increased risk of major bleeding compared to antiplatelet-assigned patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000009823DOI Listing
August 2020

Characteristics of Recurrent Ischemic Stroke After Embolic Stroke of Undetermined Source: Secondary Analysis of a Randomized Clinical Trial.

JAMA Neurol 2020 10;77(10):1233-1240

Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS.

Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke.

Design, Setting, And Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019.

Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d.

Main Outcomes And Measures: Association of recurrent ESUS with stroke characteristics.

Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively).

Conclusions And Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy.

Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2020.1995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550970PMC
October 2020

Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial.

Stroke 2020 07 10;51(7):2139-2147. Epub 2020 Jun 10.

McMaster University/Population Health Research Institute, Hamilton Health Sciences, ON, Canada (A.S., S.J.C., R.G.H.).

Background And Purpose: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source.

Methods: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily.

Results: During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7-4.3]), East Asia region (HR, 2.5 [95% CI, 1.6-3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2-3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m decrease, [95% CI, 1.0-1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2-18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin.

Conclusions: Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.027995DOI Listing
July 2020

Potential Embolic Sources and Outcomes in Embolic Stroke of Undetermined Source in the NAVIGATE-ESUS Trial.

Stroke 2020 06 16;51(6):1797-1804. Epub 2020 Apr 16.

Population Health Research Institute, Hamilton Health Sciences, ON, Canada (M.S., R.G.H.).

Background and Purpose- Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods- We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results- In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions- A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.028669DOI Listing
June 2020

Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.

Stroke 2020 03 2;51(3):938-943. Epub 2020 Jan 2.

Division of Cardiology, Population Health Research Institute, McMaster University, Hamilton, ON, Canada (S.J.C., J.S.H.).

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; =0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.028154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042078PMC
March 2020

Regional, sex, and age differences in diagnostic testing among participants in the NAVIGATE-ESUS trial.

Int J Stroke 2021 01 20;16(1):55-62. Epub 2019 Oct 20.

Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Canada.

Background And Aim: The diagnosis of embolic stroke of undetermined source (ESUS) is based on excluding other more likely stroke etiologies, and therefore diagnostic testing plays an especially crucial role. Our objective was to compare the diagnostic testing by region, sex, and age among the participants of NAVIGATE-ESUS trial.

Methods: Participants were grouped according to five global regions (North America, Latin America, Western Europe, Eastern Europe and East Asia), age (<60, 60-74, and >75 years), and sex. Frequencies of each diagnostic test within areas of echocardiography, cardiac rhythm monitoring, and arterial imaging were described and compared across groups. A multivariable logistic regression model for each diagnostic test was fit to assess the independent influence of each of region, age, and sex and likelihood of testing.

Results: We included 6985 patients in the analysis (918 from North America; 746 from Latin America; 2853 from Western Europe; 1118 from Eastern Europe; 1350 from East Asia). Average age (highest in Western Europe (69 years), lowest in Eastern Europe (65 years)), % females (highest in Latin America (44%) and lowest in East Asia (31%)), and use of each diagnostic test varied significantly across regions. Region, but not sex, was independently associated with use of each diagnostic test examined. Transesophageal echocardiography and either CT or MR angiogram were more often used in younger patients.

Conclusion: Diagnostic testing differed by region, and less frequently by age, but not by sex. Our findings reflect the existing variations in global practice in diagnostic testing in ESUS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493019884523DOI Listing
January 2021

Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial.

Stroke 2019 11 17;50(11):3184-3190. Epub 2019 Sep 17.

Department of Medicine-Neurology (R.G.H.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada.

Background and Purpose- Aortic arch atherosclerosis (AAA) is a possible source of embolism in patients with embolic stroke of undetermined source. Previous studies reported high rates of embolic events in patients with AAA, especially those with high-risk AAA. This exploratory analysis of NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) focused on patients with AAA and assessed their characteristics, stroke recurrence rates, and response to treatment. Methods- The detection of AAA and the assessment of its features were based on transesophageal echocardiography that was done in 19% of participants. AAA plaques were considered to have complex features when reported as complex or ulcerated or were ≥4 mm in thickness or had a mobile thrombus present. Results- Among 1382 participants who had transesophageal echocardiography, 397 (29%) had AAA and 112 (8%) had complex AAA. Mean (SD) age (63 [10] versus 67 [9] versus 69 [9]; <0.001), prevalence of diabetes mellitus (19% versus 26%, versus 32%; =0.002), and aortic valvulopathy (10 versus 20 versus 20; <0.001) increased across no versus noncomplex versus complex AAA, respectively. In multivariable analyses, increasing age, diabetes mellitus, aortic valvulopathy, statin use before randomization, chronic infarcts on imaging, and region were independently associated with any AAA versus no AAA and also with complex AAA versus no AAA. Multiterritorial qualifying infarcts rather than single-territory infarcts were observed in 21% with complex AAA versus 17% noncomplex versus 13% no AAA (=0.07). Annualized rates of ischemic stroke recurrence were 7.2% versus 4.2% versus 5.6% for complex versus noncomplex versus no AAA, respectively. While prevalence of complex AAA increased with increasing risk score, after adjusting for risk score, we did not observe increased risk of recurrent stroke for patients with complex AAA (hazard ratio, 1.1; 95% CI, 0.53-2.4), although the number of outcomes was limited. In patients with complex AAA, 4 strokes occurred among rivaroxaban-assigned patients and 4 strokes among aspirin-assigned patients. Conclusions- Complex AAA is prevalent in embolic stroke of undetermined source patients and is associated with atherosclerotic burden. Whether complex AAA independently increases recurrent stroke risk and whether a non-vitamin-K oral anticoagulant as compared with aspirin may be effective for reducing recurrent stroke requires additional study. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.025813DOI Listing
November 2019

Predictors of Mortality in Patients With Atrial Fibrillation (from the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ACTIVE A]).

Am J Cardiol 2018 03 11;121(5):584-589. Epub 2017 Dec 11.

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address:

The mortality rate of most patients with atrial fibrillation (AF) exceeds the stroke rate, but predictors of mortality have not been well defined. The Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A) recruited patients with AF who were unsuitable to receive vitamin K-antagonists and were randomized to aspirin alone versus aspirin plus clopidogrel. We investigated independent predictors of all-cause mortality by multivariable Cox regression analysis and explored interactions with assigned antiplatelet therapy. Of the 7,554 patients enrolled with a mean age of 71 years, 1,687 (22%) patients died during the median follow-up of 3.7 years (annualized mortality rate 6.4%/year). Assignment to dual antiplatelet therapy had no effect on mortality (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.90 to 1.1) or on vascular and nonvascular death. Independent predictors of all-cause mortality were advancing age, lower body mass index (HR 1.4 < 25 kg/m, 95% CI 1.3 to 1.6), diabetes mellitus, Latin American ethnicity (HR 1.4, 95% CI 1.1 to 1.6), previous stroke or transient ischemic attack, peripheral artery disease, increased resting heart rate (HR 1.3, 95% CI 1.1 to 1.4 per 30 bpm), lower diastolic blood pressure, coronary artery disease, heart failure, left ventricular systolic dysfunction, hemoglobin level of <13 mg/dl, and reduced estimated glomerular filtration rate. In conclusion, in this large clinical trial cohort of patients with AF, treatment with clopidogrel plus aspirin versus aspirin monotherapy did not affect all-cause mortality, vascular death, or nonvascular death. Novel independent predictors of increased mortality included lower diastolic blood pressure and Latin American ethnicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2017.11.028DOI Listing
March 2018

Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions.

Ann Neurol 2017 Aug 19;82(2):196-207. Epub 2017 Jul 19.

Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment.

Methods: SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection.

Results: CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments.

Interpretation: Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.24988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568949PMC
August 2017

Morphological classification of penetrating artery pontine infarcts and association with risk factors and prognosis: The SPS3 trial.

Int J Stroke 2016 06 8;11(4):412-9. Epub 2016 Mar 8.

Center for Brain Health, and Division of Neurology, University of British Columbia, Vancouver BC Canada

Background: Pontine infarcts are common and often attributed to small vessel disease ("small deep infarcts") or basilar branch atherosclerosis ("wedge shaped"). A well-described morphological differentiation using magnetic resonance images has not been reported. Furthermore, whether risk factors and outcomes differ by morphology, or whether infarct morphology should guide secondary prevention strategy, is not well characterized.

Methods: All participants in the Secondary Prevention of Small Subcortical Strokes Study with magnetic resonance imaging -proven pontine infarcts were included. Infarcts were classified as well-circumscribed small deep (small deep infarct, i.e. lacunar), paramedian, atypical paramedian, or other based on diffusion-weighted imaging, T2/fluid-attenuated inversion recovery, and T1-magnetic resonance images. Inter-rater reliability was high (90% agreement, Cohen's kappa = 0.84). Clinical and radiologic features independently associated with small deep infarct versus paramedian infarcts were identified (multivariable logistic regression). Differences in stroke risk and death were assessed using Cox proportional hazards.

Results: Of the 3020 patients enrolled, 644 had pontine infarcts; 619 images were available: 302(49%) small deep infarct, 245 (40%) paramedian wedge, 35 (6%) atypical paramedian, and 37 (6%) other. Among vascular risk factors, only smoking (OR 2.1, 95% CI 1.3-3.3) was independently associated with small deep infarct versus paramedian infarcts; on neuroimaging, old lacunes on T1/fluid-attenuated inversion recovery (OR 1.8, 1.3-2.6) and intracranial stenosis (any location) ≥50% (OR 0.62, 0.41-0.96). Small deep infarct versus paramedian was not predictive of either recurrent stroke or death, and there was no interaction with assigned treatment.

Conclusions: Pontine infarcts can be reliably classified based on morphology using clinical magnetic resonance images. Few risk factors differed between small deep infarct and paramedian infarcts with no differences in recurrent stroke or mortality. There was no difference in response to different antiplatelet or blood pressure treatment strategies between these two groups.

Registration: http://www.clinicaltrials.gov/NCT00059306.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493016637366DOI Listing
June 2016

Cognitive performance following lacunar stroke in Spanish-speaking patients: results from the SPS3 trial.

Int J Stroke 2015 Jun;10(4):519-28

Division of Neurology, School of Professional Psychology, Pacific University, Hillsboro, OR, USA.

Background: Cognitive impairment is frequent in lacunar stroke patients. The prevalence and pattern among Spanish-speaking patients are unknown and have not been compared across regions or with English-speaking patients.

Aims: The aim of this study was to characterize cognitive impairment in Spanish-speaking patients and compare it with English-speaking patients.

Methods: The baseline neuropsychological test performance and the prevalence of mild cognitive impairment, defined as a z-score ≤ -1.5 on memory and/or non-memory tests, were evaluated in Spanish-speaking patients in the Secondary Prevention of Small Subcortical Strokes trial.

Results: Out of 3020 participants, 1177 were Spanish-speaking patients residing in Latin America (n = 693), the United States (n = 121), and Spain (n = 363). Low education (zero- to eight-years) was frequent in Spanish-speaking patients (49-57%). Latin American Spanish-speaking patients had frequent post-stroke upper extremity motor impairment (83%). Compared with English-speaking patients, all Spanish-speaking patient groups had smaller memory deficits and larger non-memory/motor deficits, with Latin American Spanish-speaking patients showing the largest deficits median z-score -1.3 to -0.6 non-memory tests; ≤5.0 for Grooved Pegboard; -0.7 to -0.3 for memory tests). The prevalence of mild cognitive impairment was high and comparable with English-speaking patients in the United States and Latin American Spanish-speaking patients but not the Spanish group: English-speaking patients = 47%, Latin American Spanish-speaking patients = 51%, US Spanish-speaking patients = 40%, Spanish Spanish-speaking patients = 29%, with >50% characterized as non-amnestic in Spanish-speaking patient groups. Older age [odds ratio per 10 years = 1.52, confidence interval = 1.35-1.71), lower education (odds ratio 0-4 years = 1.23, confidence interval = 0.90-1.67), being a Latin American resident (odds ratio = 1.31, confidence interval = 0.87-1.98), and post-stroke disability (odds ratio Barthel Index <95 = 1.89, confidence interval = 1.43-2.50) were independently associated with mild cognitive impairment.

Conclusions: Mild cognitive impairment in Secondary Prevention of Small Subcortical Strokes Spanish-speaking patients with recent lacunar stroke is highly prevalent but has a different pattern to that observed in English-speaking patients. A combination of socio-demographics, stroke biology, and stroke care may account for these differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435833PMC
June 2015

Left Ventricular Geometry on Transthoracic Echocardiogram and Prognosis after Lacunar Stroke: The SPS3 Trial.

J Stroke Cerebrovasc Dis 2015 Jun 1;24(6):1423-9. Epub 2015 Apr 1.

Division of Neurology, Center for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: The spectrum, prevalence, and prognostic implications of abnormal left ventricular geometry (LVG) in patients with lacunar stroke are unknown. We examined the spectrum of LVG and its relationship with vascular risk factors and outcomes after lacunar stroke.

Methods: LVG was determined with transthoracic echocardiography for 1961 patients with magnetic resonance imaging-verified recent lacunar stroke participating in the Secondary Prevention of Small Subcortical Strokes trial. Multivariable logistic regression and Cox proportional hazards models were used to identify characteristics independently associated with LVG and to estimate risk from abnormal LVG for recurrent stroke and death.

Results: Abnormal LVG was present in 77%. Hispanic (odds ratio [OR], 1.4; 95% confidence interval, 1.1-1.8) or black (OR, 2.0; 1.3-2.9) race-ethnicity, diabetes (OR, 1.3; 1.0-1.7), hypertension, impaired renal function (OR, 1.8; 1.2-2.5), intracranial stenosis (OR, 1.5; 1.1-2.1), and abnormal left ventricular function (OR, 2.0; 1.4-3.0) were independently associated with abnormal LVG. Subjects with abnormal LVG also more frequently had advanced manifestations of small-vessel disease specifically previous subcortical infarcts and white matter hyperintensities. After adjusting for assigned treatments, clinical risk factors, and advanced manifestations of small-vessel disease, subjects with abnormal LVG remained at increased risk of stroke recurrence (hazard ratio, 1.5; confidence interval, 1.0-2.4). There was no interaction between LVG and assigned antiplatelet or blood pressure target. Abnormal LVG was not associated with mortality.

Conclusions: LVG consistent with chronic hypertensive changes was highly prevalent and correlated with neuroradiologic manifestations of small-vessel disease in lacunar stroke patients. These results support the constructs that both cerebral small-vessel disease and LVG represent end-organ consequences of chronic hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457650PMC
June 2015

Vertebrobasilar ectasia in patients with lacunar stroke: the secondary prevention of small subcortical strokes trial.

J Stroke Cerebrovasc Dis 2015 May 25;24(5):1052-8. Epub 2015 Mar 25.

Division of Neurology, Faculty of Medicine, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada; Division of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Background: The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke.

Methods: Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE.

Results: VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7).

Conclusions: In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.12.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408219PMC
May 2015

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

Int J Stroke 2015 Jun 3;10(4):501-5. Epub 2014 Dec 3.

Population Health Research Institute, Hamilton Health Sciences, Department of Medicine (Neurology), McMaster University, Hamilton, Ontario, Canada.

Background: Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined.

Purpose: To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin.

Methods: Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas.

Results: Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials.

Conclusions: The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12419DOI Listing
June 2015

Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial.

Lancet Neurol 2014 Dec 23;13(12):1177-85. Epub 2014 Oct 23.

Division of Neurology, Department of Medicine, Brain Research Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Background: The primary outcome results for the SPS3 trial suggested that a lower systolic target blood pressure (<130 mm Hg) might be beneficial for reducing the risk of recurrent stroke compared with a higher target (130-149 mm Hg), but that the addition of clopidogrel to aspirin was not beneficial compared with aspirin plus placebo. In this prespecified secondary outcome analysis of the SPS3 trial, we aimed to assess whether blood pressure reduction and dual antiplatelet treatment affect changes in cognitive function over time in patients with cerebral small vessel disease.

Methods: In the SPS3 trial, patients with recent (within 6 months) symptomatic lacunar infarcts from 81 centres in North America, Latin America, and Spain were randomly assigned, in a two-by-two factorial design, to target levels of systolic blood pressure (1:1; 130-149 mm Hg vs <130 mm Hg; open-label) and to a once-daily antiplatelet treatment (1:1; aspirin 325 mg plus clopidogrel 75 mg vs aspirin 325 mg plus placebo; double-blind). For this analysis, the main cognitive outcome was change in Cognitive Abilities Screening Instrument (CASI) during follow-up. Patients were tested annually for up to 5 years, during which time the mean difference in systolic blood pressure was 11 mm Hg (SD 16) between the two targets (138 mm Hg vs 127 mm Hg at 1 year). We used linear mixed models to compare changes in CASI Z scores over time. The SPS3 trial is registered with ClinicalTrials.gov, number NCT00059306.

Findings: The study took place between March 23, 2003, and April 30, 2012. 2916 of 3020 SPS3 participants (mean age 63 years [SD 11]) with CASI scores at study entry were included in the analysis, with a median follow-up of 3·0 years (IQR 1·0-4·9). Mean changes in CASI Z scores from study entry to assessment at years 1 (n=2472), 2 (n=1968), 3 (n=1521), 4 (n=1135), and 5 (n=803) were 0·12 (SD 0·83), 0·15 (0·84), 0·16 (0·95), 0·19 (0·99), and 0·14 (1·09), respectively. Changes in CASI Z scores over time did not differ between assigned antiplatelet groups (p=0·858) or between assigned blood pressure target groups (p=0·520). There was no interaction between assigned antiplatelet groups and assigned blood pressure target groups and change over time (p=0·196).

Interpretation: Cognitive function is not affected by short-term dual antiplatelet treatment or blood pressure reduction in fairly young patients with recent lacunar stroke. Future studies of cognitive function after stroke should be of longer duration or focus on patients with higher rates of cognitive decline.

Funding: US National Institute of Neurological Disorders and Stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(14)70224-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284947PMC
December 2014

Clinical correlates of infarct shape and volume in lacunar strokes: the Secondary Prevention of Small Subcortical Strokes trial.

Stroke 2014 Oct 4;45(10):2952-8. Epub 2014 Sep 4.

From the Division of Neurology, Department of Medicine, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada (N.A., M.N., T.S.F., F.C., O.R.B.); Biostatistics Consultant, Minot, ND (L.A.P.); Department of Radiology, University of Texas Health Sciences Centre, San Antonio (C.B.); Department of Biostatistics, University of Alabama at Birmingham (L.A.M.); Department of Neurology, Hennepin County Medical Center and the University of Minnesota, Minneapolis (D.C.A.); Division of Neurology, Department of Medicine, McMaster University, Hamilton, Ontatio, Canada (R.G.H.); SPS3 Coordinating Center (N.A., L.A.P., M.N., T.S.F., C.B., F.C., R.G.H., O.R.B.); and SPS3 Statistical Center (L.A.M.).

Background And Purpose: Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes.

Methods: We studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on diffusion-weighted imaging. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3-dimensional reconstruction of axial MRI slices.

Results: Infarct shape was ovoid/spheroid in 63%, slab in 12%, stick in 7%, and multicomponent in 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 mL, respectively (P<0.001). Distributions of vascular risk factors were similar across the 4 groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multicomponent had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (P=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred during an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume.

Conclusions: In patients with recent lacunar stroke, vascular risk factor profile was similar among the different infarct shapes and sizes. Infarct size correlated with worse short-term functional outcome. Neither shape nor volume was predictive of stroke recurrence.

Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.114.005211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198938PMC
October 2014

Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial.

Stroke 2014 Oct 26;45(10):2989-94. Epub 2014 Aug 26.

From the Divisions of Neurology (M.S., R.G.H.) and Cardiology (S.J.C.), Department of Medicine, McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; Biostatistics Consultant, Minot, ND (L.A.P.); Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada (O.R.B.); Department of Neurology, University of Minnesota, Minneapolis (D.C.A.); Department of Neurology, University of Texas Health Science Center, San Antonio (S.P.); and Department of Biostatistics, University of Iowa, Iowa City (C.S.C.).

Background And Purpose: The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population.

Methods: We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial.

Results: During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin<13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m2 decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001).

Conclusions: Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain.

Clinical Trial Registration Url: http://www.SPS3ClinicalTrials.gov. Unique identifier: NCT00059306.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.114.005789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175186PMC
October 2014

Cardiac troponin changes to distinguish type 1 and type 2 myocardial infarction and 180-day mortality risk.

Eur Heart J Acute Cardiovasc Care 2014 Dec 25;3(4):317-25. Epub 2014 Jun 25.

Cardiac Biomarkers Trials Laboratory, Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis, USA Department of Laboratory Medicine and Pathology, Hennepin County Medical Center and University of Minnesota, Minneapolis, USA

Aims: To determine the ability of serial cardiac troponin (cTnI) changes (delta) to distinguish type 1 and type 2 myocardial infarction (MI) (excluding all ST-segment elevation MIs (STEMIs)) and describe the diagnostic accuracy and 180-day mortality in MI versus no-MI patients.

Methods And Results: Serial cTnIs were measured in 1112 consecutive patients without STEMI and within 6h of presentation to a United States emergency department: 856 (77%) with no MI, 66 (6%) type 1 MI, and 190 (17%) type 2 MI. Of the 0 to 3h and 0 to 6h absolute and relative cTnI changes, only the distribution of absolute change from 0 to 6h was significantly different between type 1 and type 2 MI: median (interquartile range) 311 (1430) ng/l vs. 80 (330) ng/l, p=0.03. Neither the absolute concentration change nor the absolute percent change from either 0 h to 3h (areas under the curves (AUCs) 0.57 and 0.54 respectively) or 0 h to 6h (AUCs 0.60 and 0.51) improved on the performance of the individual cTnI results at 3h (AUC 0.60) or 6h (AUC 0.62), respectively. After adjusting for age, and histories of heart failure and renal insufficiency, those with type 2 MI (hazard ratio 2.9, 95% confidence interval (CI) 1.4-5.9, p=0.004) and those with no index MI and cTnI(max0-6h) > 34 ng/l (2.5, CI 1.1-6.0, p=0.04) had increased risk of death within 180 days compared with those with no MI and cTnI(max 0-6h) ≤ 34 ng/l.

Conclusion: Delta cTnI did not aid in distinguishing type 1 MI from the more common type 2 MI. Patients diagnosed with type 2 MIs, which represented more than half of all index MIs, had increased risk of death after discharge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2048872614538411DOI Listing
December 2014

Vitamin K antagonists and risk of subdural hematoma: meta-analysis of randomized clinical trials.

Stroke 2014 Jun 13;45(6):1672-8. Epub 2014 May 13.

From the Population Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada (B.J.C., R.G.H.); and Biostatistics Consultant, Minot, ND (L.A.P.).

Background And Purpose: Subdural hematomas are an important bleeding complication of anticoagulation. We quantify the risk of subdural hematoma associated with anticoagulation with vitamin K antagonists (VKAs) compared with other oral antithrombotic therapies.

Methods: Randomized trials were identified from the Cochrane Central Register of Controlled Trials and were included if published since 1980 and compared oral VKAs with antiplatelet therapy or with direct-acting oral anticoagulants. Two reviewers independently extracted data with differences resolved by joint review.

Results: Nineteen randomized trials were included that involved 92 156 patients and 275 subdural hematomas. By meta-analysis, VKAs were associated with a significantly increased risk of subdural hematoma (odds ratios, 3.0; 95% confidence interval, 1.5-6.1) compared with antiplatelet therapy (9 trials, 11 603 participants). The risk of subdural hematoma was also significantly higher with VKAs versus factor Xa inhibitors (meta-analysis odds ratios, 2.9; 95% confidence interval, 2.1-4.1; 5 trials, 49 687 patients) and direct thrombin inhibitors (meta-analysis odds ratios, 1.8; 95% confidence interval, 1.2-2.7; 5 trials, 30 866 patients) versus VKAs. The absolute rate of subdural hematoma among 24 485 patients with atrial fibrillation treated with VKAs pooled from 6 trials testing direct-acting oral anticoagulants was 2.9 (95% confidence interval, 2.5-3.5) per 1000 patient-years.

Conclusions: VKA use significantly increases the risk of subdural hematoma by ≈3-fold relative to antiplatelet therapy. Direct-acting oral anticoagulants are associated with a significantly reduced risk of subdural hematomas versus VKAs. Based on indirect comparisons to VKAs, the risks of subdural hematoma are similar with antiplatelet monotherapies and factor Xa inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.114.005430DOI Listing
June 2014

Clinical-MRI correlations in a multiethnic cohort with recent lacunar stroke: the SPS3 trial.

Int J Stroke 2014 Dec 27;9(8):1057-64. Epub 2014 May 27.

Department of Medicine, Division of Neurology, Brain Research Center, University of British Columbia, Vancouver, Canada.

Background: Neuroimaging manifestations of small vessel disease are heterogeneous, and correlation with patient features has not been adequately characterized.

Aim: Our goal was to correlate magnetic resonance imaging findings with clinical features in a large multiethnic cohort with recent lacunar stroke.

Methods: Patient characteristics were correlated with neuroimaging results in the Secondary Prevention of Small Subcortical Stroke study participants.

Results: Among 3005 patients, mean age was 63 years; 62% were men; and 51%, 30%, and 16% were non-Hispanic White, Hispanic, and Black, respectively. Recent lacunar infarcts were distributed between the subcortical hemisphere (31%), thalamus (26%), brainstem/cerebellum (26%), and basal ganglia/internal capsule (16%). Multiple lacunar infarcts (i.e., acute and remote) were present in 40% and associated with increased age (OR 1·3 per 20 years, 95% CI 1·1, 1·5), male gender (OR 1·5, CI 1·3, 1·7), hypertension (OR 1·5, CI 1·2, 1·8), increased systolic blood pressure (OR 1·2 per 20 mmHg, CI 1·1, 1·3), and prior stroke (OR 3·8, CI 2·9, 5·0). Moderate-severe white matter hyperintensities were present in 50% and associated with increased age (OR 4·3 per 20 years, CI 3·4, 5·4), hypertension (OR 1·8, CI 1·4, 2·3), increased systolic blood pressure (OR 1·3 per 20 mmHg, CI 1·1, 1·5), increased diastolic blood pressure (OR 1·2 per 10 mm, CI 1·0, 1·3), and prior stroke (OR 3·3, CI 2·3, 4·5). Infarct location varied significantly by race-ethnicity (P < 0·001), with Blacks and Hispanics having more infarcts in the brainstem/cerebellum than non-Hispanic Whites, and by gender with women more often having thalamic lacunes than men (P ≤ 0·001).

Conclusions: In patients with recent lacunar stroke, infarct location and number have distinctie associations with gender, vascular risk factors, and race-ethnicity, demonstrating the complex pathogenesis of lacunar stroke and cerebral small artery disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12282DOI Listing
December 2014

The relevance of living supports on antiplatelet adherence and trial participation: the SPS3 trial.

Int J Stroke 2014 Jun 24;9(4):443-8. Epub 2014 Mar 24.

Division of Neurology, Brain Research Center, The University of British Columbia, Vancouver, BC, Canada.

Background: While living with others has been associated with improved functional outcome after acute stroke, it is unclear if this affects adherence to stroke prevention measures.

Aims: We examined the relationship between living arrangements and adherence to antiplatelet therapy assignment and participation status in an international randomized trial for secondary stroke prevention.

Method: Antiplatelet therapy adherence, trial retention outcomes, and baseline characteristics for participants enrolled in the Secondary Prevention of Small Subcortical Strokes study were compared between those who lived alone vs. with others (n = 2374). Participant status at end-of-trial was categorized into (1) on assigned antiplatelet, (2) off assigned antiplatelet by participant request, or (3) participant withdrew consent/lost to follow-up. Multivariable multivariate logistic regression was used to identify patient features at entry predictive of participant status at trial end.

Results: Living arrangement, alone vs. with other(s), was not significantly associated with participant status. Participants enrolled in the United States/Canada (odds ratio 3.1, confidence intervals 2.0-5.0, vs. Latin America), taking more (7+) prescription medications (odds ratio 1.7, confidence intervals 1.1-2.7, vs. 0-2 medications), and scoring lower on the Stroke Specific Quality of Life scale (odds ratio 1.3, confidence intervals 1.1-1.5, per 10 points) were more likely to withdraw or become lost to follow-up in the study vs. completing the study on assigned antiplatelet therapy. Participants enrolled in the United States/Canada (odds ratio 5.0, confidence intervals 2.4-10.0, vs. Latin America) and taking fewer (0-2) medications (odds ratio 1.9, confidence intervals 1.2-3.1 vs. 3-6 medications) were more likely to request discontinuation of assigned antiplatelet medication vs. completing the study.

Conclusion: Living with others was not independently predictive of protocol adherence in this cohort. Number of medications and Stroke Specific Quality of Life scale score may be more indicative of likelihood of trial participation and acceptance of long-term antiplatelet regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167670PMC
June 2014

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

J Stroke Cerebrovasc Dis 2014 Apr 22;23(4):618-24. Epub 2013 Jun 22.

Department of Neurology, University of Minnesota, Minneapolis, Minnesota.

Background: Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status.

Methods: Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes.

Results: Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status.

Conclusions: In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858405PMC
April 2014

Effect of addition of clopidogrel to aspirin on stroke incidence: Meta-analysis of randomized trials.

Int J Stroke 2015 Jul 22;10(5):686-91. Epub 2013 May 22.

Department of Medicine (Neurology), Brain Research Center, University of British Columbia, Vancouver, BC, Canada.

Background: It remains controversial whether dual antiplatelet therapy reduces stroke more than aspirin alone.

Aim: We aimed to assess the effects of adding clopidogrel to aspirin on the occurrence of stroke and major haemorrhage in patients with vascular disease.

Methods: Meta-analysis of published randomized trials comparing the combination of clopidogrel and aspirin vs. aspirin alone that reported stroke and major bleeding.

Results: Thirteen randomized trials were included with a total of 90 433 participants (mean age 63 years; 63% male) with a mean follow-up of 1·0 years and 2011 strokes. Stroke was reduced 19% by dual antiplatelet therapy (odds ratio = 0·81, 95% confidence interval 0·74-0·89) with no evidence of heterogeneity of effect across different trial populations (I(2) index = 5%, P = 0·4 for heterogeneity). Dual antiplatelet therapy reduced ischemic stroke by 23% (odds ratio = 0·77; 95% confidence interval 0·70-0·85); there was a nonsignificant 12% increase in intracerebral haemorrhage (odds ratio = 1·12, 95% confidence interval 0·86-1·46). Among 1930 participants with recent (<30 days) brain ischemia from four trials, stroke was reduced by 33% (odds ratio = 0·67, 95% confidence interval 0·46-0·97) by dual antiplatelet therapy vs. aspirin alone. The risk of major bleeding was increased by 40% (odds ratio = 1·40, 95% confidence interval 1·26-1·55) by dual antiplatelet therapy.

Conclusions: This meta-analysis demonstrates a substantial relative risk reduction in stroke by clopidogrel plus aspirin vs. aspirin alone that is consistent across different trial cohorts. Major haemorrhage is increased by dual antiplatelet therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijs.12050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971006PMC
July 2015

Aspirin therapy and risk of subdural hematoma: meta-analysis of randomized clinical trials.

J Stroke Cerebrovasc Dis 2013 May 16;22(4):444-8. Epub 2013 Feb 16.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: Subdural hematomas are an important bleeding complication of antithrombotic therapies. We sought to characterize the risk of subdural hematoma associated with antiplatelet therapy.

Methods: Trials were gathered from the Cochrane Central Register of Controlled Trials and from recent meta-analyses of trials regarding antiplatelet therapy for the primary prevention of stroke. Randomized trials published since 1980 comparing antiplatelet therapy with placebo or control and reporting subdural hematoma were included in the analysis. For recent large trials that did not report subdural hematomas, unpublished results were sought. Two reviewers independently extracted data on study design and subdural hematomas, with differences resolved by joint review and consensus.

Results: Four published trials were identified that compared aspirin with placebo/control involving 6565 participants (mean age 66 years) with 8 total subdural hematomas. Unpublished data from 5 aspirin trials with 90,689 participants reported 18 total subdural hematomas. The incidence of subdural hematomas varied from 0.02 per 1000 patient-years for primary prevention trials of middle-aged health professionals to 1 to 2 per 1000 patient-years for older patients with atrial fibrillation. Pooled data from all 9 trials revealed an odds ratio of 1.6 (95% confidence interval 0.8-3.5; heterogeneity P = .8; I(2) index 0%) for antiplatelet therapy and risk of subdural hematoma.

Conclusions: Based on the limited available data, it is uncertain whether aspirin therapy increases the risk of subdural hematoma: the observed 1.6-fold increased risk was not statistically significant. The incidence of subdural hematoma during aspirin therapy is low but varies widely depending upon the age of the patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.01.007DOI Listing
May 2013

Cognitive impairment in lacunar strokes: the SPS3 trial.

Ann Neurol 2012 Sep;72(3):351-62

Division of Neurology, Department of Medicine, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Lacunar strokes are a leading cause of cognitive impairment and vascular dementia. However, adequate characterization of cognitive impairment is lacking. The aim of this study was to estimate the prevalence and characterize the neuropsychological impairment in lacunar stroke patients.

Methods: All English-speaking participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (National Clinical Trial 00059306) underwent neuropsychological testing at baseline. Raw scores were converted to z scores using published norms. Those with impairment (z ≤ -1.5) in memory and/or nonmemory domains were classified as having mild cognitive impairment (MCI).

Results: Among the 1,636 participants, average z scores on all tests were < 0, with the largest deficits seen on tests of episodic memory (range of means, -0.65 to -0.92), verbal fluency (mean, -0.89), and motor dexterity (mean, -2.5). Forty-seven percent were classified as having MCI (36% amnestic, 37% amnestic multidomain, 28% nonamnestic). Of those with modified Rankin score 0-1 and Barthel score = 100, 41% had MCI. Younger age (odds ratio [OR] per 10-year increase, 0.87), male sex (OR, 1.3), less education (OR, 0.13-0.66 for higher education levels compared to 0-4 years education), poststroke disability (OR, 1.4), and impaired activities of daily living (OR, 1.8) were independently associated with MCI.

Interpretation: In this large, well-characterized cohort of lacunar stroke patients, MCI was present in nearly half, including many with minimal or no physical disabilities. Cognitive dysfunction in lacunar stroke patients may commonly be overlooked in clinical practice but may be as important as motor and sensory sequelae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.23733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198173PMC
September 2012

Sex, stroke, and atrial fibrillation.

Arch Neurol 2012 Dec;69(12):1641-3

Context: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause.

Objective: To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level.

Design, Setting, And Patients:   Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases.

Main Outcome Measures:   Risk of stroke.

Results: The cohort comprised 39 398 men (47.2%) and 44 115 women (52.8%). At admission, women were older and had a higher CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS2 score, and warfarin treatment.

Conclusion: Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archneurol.2012.2691DOI Listing
December 2012

Diagnosis of ST-elevation myocardial infarction in the presence of left bundle branch block with the ST-elevation to S-wave ratio in a modified Sgarbossa rule.

Ann Emerg Med 2012 Dec 31;60(6):766-76. Epub 2012 Aug 31.

Hennepin County Medical Center, Minneapolis, MN, USA.

Study Objective: Sgarbossa's rule, proposed for the diagnosis of acute myocardial infarction in the presence of left bundle branch block, has had suboptimal diagnostic utility. We hypothesize that a revised rule, in which the third Sgarbossa component (excessively discordant ST-segment elevation as defined by ≥5 mm of ST-segment elevation in the setting of a negative QRS) is replaced by one defined proportionally by ST-segment elevation to S-wave depth (ST/S ratio), will have better diagnostic utility for ST-segment elevation myocardial infarction (STEMI) equivalent, using documented coronary occlusion on angiography as reference standard.

Methods: We collected admission ECGs for all patients with an acutely occluded coronary artery and left bundle branch block at 3 institutions. The ECGs of emergency department patients with chest pain or dyspnea and left bundle branch block, but without coronary occlusion, were used as controls. The R or S wave, whichever was most prominent, and ST segments, relative to the PR segment, were measured to the nearest 0.5 mm. The ST/S ratio was calculated for each lead that has both discordant ST deviation of greater than or equal to 1 mm and an R or S wave of opposite polarity; others were set to 0. The cut point for the most negative ST/S ratio with at least 90% specificity was determined. The revised rule is unweighted, requiring just 1 of 3 criteria. Diagnostic utilities of the original and revised Sgarbossa rules were computed and compared. McNemar's test was used to compare sensitivities and specificities.

Results: The study and control groups included 33 and 129 ECGs, respectively. The cut point selected for relative discordant ST-segment elevation was -0.25. Excessive absolute discordant ST-segment elevation of 5 mm was present in at least one lead in 30% of ECGs in patients with confirmed coronary occlusion versus 9% of the control group, whereas excessive relative discordant ST-segment elevation less than -0.25 was present in 79% vs. 9% [corrected].Sensitivity of the revised rule in which ST-segment elevation with an ST/S ratio less than or equal to -0.25 replaces ST-segment elevation greater than or equal to 5 mm was significantly greater than either the weighted (P<.001) or unweighted (P=.008) Sgarbossa rule: 91% (95% confidence interval [CI] 76% to 98%) versus 52% (95% CI 34% to 69%) versus 67% (95% CI 48% to 82%). Specificity of the revised rule was lower than that of the weighted rule (P=.002) and similar to that of the unweighted rule (P=1.0): 90% (95% CI 83% to 95%) versus 98% (95% CI 93% to 100%) versus 90% (95% CI 83% to 95%). Positive and negative likelihood ratios for the revised rule were 9.0 (95% CI 8.0 to 10) and 0.1 (95% CI 0.03 to 0.3). The revised rule was significantly more accurate than both the weighted (16% difference; 95% CI 5% to 27%) and unweighted (12% difference; 95% CI 2% to 22%) Sgarbossa rules.

Conclusion: Replacement of the absolute ST-elevation measurement of greater than or equal to 5 mm in the third component of the Sgarbossa rule with an ST/S ratio less than -0.25 greatly improves diagnostic utility of the rule for STEMI. An unweighted rule using this criterion resulted in excellent prediction for acute coronary occlusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annemergmed.2012.07.119DOI Listing
December 2012
-->