Age and risk of stroke in atrial fibrillation: evidence for guidelines?

AIM: Guidelines for the clinical management of patients with atrial fibrillation suggest that treatment strategies for prescribing oral anticoagulant therapy should implicate change at age 60, 65 and 75 years. We examined if there is any threshold concerning risk of stroke by age. METHODS: We identified 141,493 subjects, aged 40-89 years, with an incident hospital diagnosis of nonvalvular atrial fibrillation or flutter and no previous or concomitant diagnosis of stroke in the Danish National Registry of Patients from January 1, 1980, to December 31, 2002. The subjects were followed in the Danish National Registry of Patients for the occurrence of an incident diagnosis of stroke of any nature and in the Danish Civil Registration System for emigration and vital status. We examined the risk of stroke by age in men and women using Cox regression models, which included age categorized in intervals, linear splines of age with cut points at age 60 and 75 years, or at age 65 and 75 years. We also analyzed age as a continuous variable in linear and polynomial regression models. RESULTS: During follow-up 15,964 incident strokes were reported to the Danish National Registry of Patients. The risk of stroke increased by increasing age at baseline. We did not find any evidence for a threshold concerning risk of stroke by age, and the best model fit was obtained in a third-order polynomial regression model. CONCLUSION: The risk of stroke increased gradually by increasing age, and we could not detect any threshold concerning risk of stroke by age.     

Seasonal variation in stroke and stroke-associated mortality in patients with a hospital diagnosis of nonvalvular atrial fibrillation or flutter. A population-based study in Denmark

AIM: There are few data on seasonal variation in stroke and seasonal variation in mortality after stroke in patients with atrial fibrillation. We examined the seasonal pattern in stroke occurrence and the effect of the season on mortality after stroke in patients with a history of nonvalvular atrial fibrillation. METHODS: We identified all individuals, aged 40-89 years, with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) in the 1980-2002 period and no history of heart valve disease and a previous or concomitant diagnosis of atrial fibrillation or flutter in the Danish National Registry of Patients. Subjects were followed in the Danish Civil Registration System for emigration and vital status. We used periodic regression models to estimate the peak-trough ratio stratified by sex, age and comorbid medical conditions. Seasonal effect on mortality after stroke was analyzed in a Cox proportional hazards model. RESULTS: The relative incidence of stroke estimated as the ratio of the incidence in the month of the peak (January) to the incidence in the month of the trough (July) was 1.11 (95% confidence interval: 1.07-1.15). The relative incidence of stroke was similar for men and women, did not differ by age (stratified by age 75 years) and was essentially similar for comorbid conditions considered. There was no seasonal effect on mortality after stroke. CONCLUSIONS: The occurrence of stroke in patients with atrial fibrillation is modestly higher during the winter. Stroke-associated mortality does not vary by season.     

Ability of the DANCAMI to predict the risk ischemic stroke and mortality in patients with atrial fibrillation/flutter

ObjectivesComparison of the danish comorbidity index for acute myocardial infarction (DANCAMI), the charlson comorbidity index (CCI), the elixhauser comorbidity index (ECI), and the CHA₂DS₂-VASc score to predict ischemic stroke, cardiovascular mortality, and all-cause mortality after atrial fibrillation/flutter.Materials and MethodsA population-based cohort study of all Danish patients with incident atrial fibrillation/flutter during 2000–2020 (n=361,901). C-Statistics were used to evaluate the discriminatory performance for predicting 1 and 5-year risks of the outcomes for a baseline model (including age and sex) +/- the individual indices.ResultsFor the DANCAMI, the 5-year risk did not increase with comorbidity burden for ischemic stroke (5.9% for low vs. 5.6% for severe) but did increase for cardiovascular mortality (10% for low vs. 16% for severe) and all-cause mortality (33% for low vs. 61% for severe). C-Statistics for predicting 5-year ischemic stroke risk were similar for all models (0.64). C-Statistics for predicting 5-year cardiovascular mortality risk were also similar for the baseline (0.76), the DANCAMI (0.77), the CCI (0.76), the ECI (0.76), and the CHA₂DS₂-VASc (0.76) models. C-Statistics for predicting 5-year all-cause mortality risk were lower for the baseline (0.71) and the CHA₂DS₂-VASc (0.71) models than for the DANCAMI (0.75), the CCI (0.74), and the ECI (0.74) models. The 1-year C-Statistics were comparable.ConclusionThe DANCAMI predicted ischemic stroke and cardiovascular mortality risks similar to the CCI, the ECI, and the CHA₂DS₂-VASc. The DANCAMI predicted all-cause mortality risk similar to the CCI and the ECI, but better than the baseline and the CHA₂DS₂-VASc.     

Burden of Premature Atrial Complexes and Risk of Recurrent Stroke and Death in Patients with Mild to Moderate Ischemic Stroke

BackgroundPremature atrial complexes (PACs) meet increased attention as a potential intermediary between sinus rhythm and atrial fibrillation (AF). Patients with even high numbers of PACs do not fulfill current guidelines for oral anticoagulation treatment though an associated stroke risk is suspected. Objective: We aimed to determine whether a high number of PACs or runs of AF less than 30 seconds in 2-day continuous electrocardiogram (ECG) recording was associated with risk of recurrent ischemic stroke/transient ischemic attack (TIA) or death in a large cohort of patients with acute ischemic stroke or TIA and no prior AF.MethodsWe performed 48 hours continuous ECG recording within 1 week after ischemic stroke/TIA. PACs were reported as mean number of PACs per hour. Patients were followed in Danish Stroke Registry, Danish Civil Registration System, and Danish National Patient Registry. Cox Regression analysis was used to calculate hazard ratios.ResultsWe included 1507 patients with TIA (40%) or ischemic stroke (60%), of which 98.7% had mild to moderate strokes. Mean age was 72.9 (7.8) years, 43.4% were females. Follow-up was 2.3 (1.3) years. Hazard ratio for recurrent stroke/TIA or death did not differ between quartiles of PAC burden, nor did any of the 2 components of this composite endpoint. Nonsustained AF less than 30 seconds was not associated with higher risk of recurrent stroke/TIA or death.ConclusionsIn a large cohort of patients with recent ischemic stroke or TIA, burden of PACs or nonsustained AF less than 30 seconds were not associated to higher risk of recurrent stroke/TIA or death.     

Severity of coronary atherosclerosis and stroke incidence in 7-year follow-up

The purpose of this prospective study was to investigate the association between the severity of coronary atherosclerosis in angiography and the risk of stroke in symptomatic coronary artery disease (CAD) patients without atrial fibrillation or atrial flutter. Associations between stroke and coronary artery disease were examined in 1,183 subjects without a history of stroke and who were referred for diagnostic coronary angiography. Association between stoke and coronary artery disease was determined using the COX proportional hazard regression model. During the follow-up period (mean 6.7 years), 50 strokes occurred. In the group with strokes there was a higher prevalence of multi-vessel coronary artery disease (62 vs. 46 %, p < 0.01). In the COX proportional hazard regression model, multi-vessel CAD was significantly associated with the stroke hazard ratio (HR) of 1.8 (CI 1.03–3.43), determined from a 7-year period of observation. Symptomatic patients with multi-vessel CAD are thus at a high risk of stroke development.     

Pharmacotherapy for Patients with Atrial Fibrillation and Cerebral Microbleeds

Background: Patients with cerebral microbleeds have increased risk of intracranial hemorrhage and ischemic stroke. No trial specifically informs antithrombotic therapy for patients with cerebral microbleeds and atrial fibrillation. We investigated the safety of anticoagulation versus no anticoagulation with regard to cerebrovascular outcomes and mortality. Methods: All consecutive atrial fibrillation patients from 2015 to 2018 with MRI evidence of ≥1 cerebral microbleed at time of imaging were reviewed. Patients were treated with warfarin, direct oral anticoagulants, or neither. Primary outcome was all-cause mortality informed by National Death Registry and the composite of ischemic and hemorrhagic stroke. All statistical tests were 2-sided and significant at P < .05. Results: The median interval from patient identification until the end of electronic health record surveillance was 9.93 months (interquartile range, 2.83-19.17 months). We identified 308 atrial fibrillation patients with cerebral microbleeds; 128(41.6%) were on warfarin, 88(28.6%) on direct oral anticoagulants, and 92(29.9%) on neither. Over the surveillance interval, 87 deaths, 51 ischemic strokes, and 14 hemorrhagic strokes occurred. The estimated likelihoods of the composite stroke outcome and ischemic stroke only did not differ significantly among the 3 groups. However, patients taking direct oral anticoagulants had a significantly smaller likelihood of all-cause mortality than patients who were not anticoagulated (adjusted hazard ratio: .44[.23, .83], P=.012). Conclusions: In patients with coprevalent atrial fibrillation and cerebral microbleeds, we did not detect differences in subsequent ischemic stroke, hemorrhagic stroke, or both, comparing warfarin, direct oral anticoagulants, or neither. Patients treated with direct oral anticoagulants had better survival than nonanticoagulated patients.     

Atrial fibrillation after stroke in the elderly

To examine the relationship between atrial fibrillation and mortality after stroke, we studied 186 men and 167 women from the Waikato Stroke Registry whose mean age was 75.2 +/- 7.5 years. Twenty-three percent (82 of 353) had atrial fibrillation or flutter on their admission electrocardiogram. This group differed significantly from that with sinus rhythm in three respects: 1) They were older (p less than 0.01); 2) they had more severe current stroke deficit as evidenced by lower limb power (p less than 0.05) and Mini-Mental State Score (p less than 0.001), higher incidence of homonomous hemianopia (p less than 0.05), and lower incidence of lacunar syndrome stroke (p less than 0.001); and 3) they had a significantly higher incidence of cardiomegaly and congestive heart failure (p less than 0.01). Functional outcome was insignificantly better in the group with sinus rhythm. During a mean follow-up period of 18 months, mortality was significantly higher in the group with atrial fibrillation (p = 0.001). Proportional hazards modeling, however, showed that the apparently poorer survival in those patients with atrial fibrillation could be explained by factors other than cardiac rhythm, such as age, Mini-Mental State Score, level of consciousness, and interstitial edema on admission chest radiograph. Thus, atrial fibrillation was not an independent predictor of survival after stroke.     

Risk factors for stroke and other embolic events in patients with nonrheumatic atrial fibrillation

Factors associated with stroke and other cardiac embolic events in subjects with nonrheumatic atrial fibrillation were examined in a retrospective study of 91 patients from a teaching hospital clinic. There were 28 first strokes during 355 person-years of follow-up (7.9 per 100 person-years). Patients who had experienced one or more previous events were approximately 2.3 times more likely to have a subsequent event (hazard ratio 2.3, 95% confidence interval 1.5-3.4) than patients who had experienced no events. A univariate analysis of factors associated with a first stroke of any cause or other embolic event showed that age of greater than 75 years (hazard ratio 2.5) and systolic blood pressure of greater than 160 mm Hg (hazard ratio 6.4) were significant factors. After adjusting for the effect of age and systolic blood pressure, previous events still carried an increased risk for subsequent events. Subject with nonrheumatic atrial fibrillation who have had one or more embolic events are at high risk of further emboli. They require special consideration when treatment is being planned.     

The Danish Multiple Sclerosis Registry: a 50-year follow-up.

The Danish Multiple Sclerosis Registry was established in 1948 in continuation with a nationwide survey of the prevalence of Multiple Sclerosis (MS) in Denmark. The register has since collected information on MS patients from all Danish departments of neurology, practising neurologists, MS rehabilitation centres, the National Patient Registry, the Danish MS Society, and departments of neuropathology. The registry is linked with the Danish Central Population Registry. The completeness has been estimated at more than 90%. All cases are reclassified by two neurologists as to diagnosis and year of onset. 12 070 cases with a confirmed diagnosis of MS are kept in the databases. They were prevalent in 1949 or have had onset in the period 1948 - 1993. The registry is continuously updated with new information on registered cases and new cases. The crude average annual incidence rate 1980 - 89 was 4.99/105; the prevalence rate was 112/105 by 1 January 1990. Cross-linking with other registers have enabled analytical prospective epidemiological studies, and the registry has provided population based unbiased samples of patients for a number of clinical studies.     

Epidemiology of multiple sclerosis: incidence and prevalence rates in Denmark 1948–64 based on the Danish Multiple Sclerosis Registry

The Danish Multiple Sclerosis Registry (DMSR) is a national register based upon the ethnically homogeneous Danish population of about 5 millions. The DMSR was founded in 1956 following a nationwide Danish prevalence survey of MS in 1949 and a continuous registration of incident cases of MS since January 1, 1948. Included in DMSR are all Danish cases of MS (or suspicion of MS) diagnosed by a neurologist or a department of neurology. The sources of notification are the 22 neurological departments in Denmark, the National Patient Registry, the neuropathological departments, the Registry of Causes of Death, and, up to 1975, the Disablement Insurance Court. Notified cases which do not comply with the standardized diagnostic criteria of the DMSR are excluded. An estimate of the completeness of the DMSR is 90-95% and the validity is around 94%. Age- and sex-specific incidence rates of MS for the interval 1948-64 are presented. The crude annual incidence rate of MS in Denmark was in the year 1948-64 4.42 per 100,000 population, 22% higher in females than males. There was a significant geographical variation of incidence rates and a significant downward trend in incidence rates during the interval, whereas the prevalence rates showed a slight increase.     

Antithrombotic and interventional treatment options in cardioembolic transient ischaemic attack and ischaemic stroke

Peer-reviewed data pertaining to anti-thrombotic and interventional therapy for transient ischaemic attack (TIA) or ischaemic stroke patients with non-valvular atrial fibrillation, atrial flutter, interatrial septal abnormalities, or left ventricular thrombus were reviewed. Long-term oral anticoagulant therapy with warfarin is the treatment of choice for secondary stroke prevention following TIA or minor ischaemic stroke in association with persistent or paroxysmal non-valvular atrial fibrillation or atrial flutter. If warfarin is contraindicated, long-term aspirin is a safe, but much less effective alternative treatment option in this subgroup of patients with cerebrovascular disease. Management of young patients with TIA or stroke in association with an interatrial septal defect is controversial. Various treatment options are outlined, but readers are encouraged to include these patients in one of the ongoing randomised clinical trials in this area. It is reasonable to consider empirical anticoagulation in patients with TIA or ischaemic stroke in association with left ventricular thrombus formation following myocardial infarction or in association with idiopathic dilated cardiomyopathy. If warfarin is prescribed, one should aim for a target international normalised ratio of 2.5 (range 2-3) to achieve the best balance between adequate secondary prevention of cardioembolic events and the risk of major haemorrhagic complications.     

High case-fatality rates in the Warsaw stroke registry

We studied 1-year survival in 297 patients with first-even-in-lifetime ischemic stroke (FEL-IS) selected from a population-based study of stroke in the Mokotow district of Warsaw. Case fatality rates were 29% at 30 days and 51% at 1 year. These case fatality rates are significantly higher than in other industrialized countries. Early deaths were primarily caused by neurological sequelae of stroke or complications of immobility, whereas late deaths (>30 days) were primarily caused by stroke recurrence or complications of immobility. Predictors of survival were analyzed by life table methods. Adverse predictors of 1-year survival included greater age, low activities of daily living scores, atrial fibrillation, greater weakness, congestive heart failure, and untreated hypertension. Patients with stroke recurrence were more likely to die in the first year. We hypothesize that stroke severity contributes to high case-fatality rates by increasing death caused by both direct neurological sequelae and complications of immobility. Medical comorbidity probably contributes to high case-fatality rates in Poland by increasing stroke recurrence rates and by increasing deaths caused by immobility. We hypothesize that high case-fatality rates in Poland could be reduced by improved rehabilitation of stroke patients to avoid deaths caused by immobility and by better control of medical comorbidity in stroke patients.     

Early apixaban therapy after ischemic stroke in patients with atrial fibrillation

Journal of Neurology - The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown. We aimed to objectively assess the rate of radiological hemorrhagic...     

Stroke in parents who lost a child: a nationwide follow-up study in Denmark

The association between psychological stress and stroke remains uncertain. We therefore examined whether or not one of the most extreme psychological stressors, the death of a child, was associated with the risk of stroke in a nationwide population-based follow-up study. All 21,062 parents who lost a child in Denmark during 1980-1996 were compared with 293,745 parents who had not lost a child. The overall adjusted relative risk (RR) of stroke was 1.00 (95% CI = 0.83-1.20) among the exposed after up to 18 years of follow-up. The RRs for fatal stroke and nonfatal stroke were 0.69 (95% CI = 0.37-1.26) and 1.03 (95% CI = 0.85-1.24), respectively. The RRs for hemorrhagic and nonhemorrhagic stroke were 1.02 (95% CI = 0.77-1.36) and 0.94 (95% CI = 0.74-1.20), respectively. The risk of stroke did not differ irrespective of whether the death of the child was unexpected or not. The death of a child was not associated with any substantially increased risk of stroke in the bereaved parents.     

Occult lung cancer manifesting within the first year after stroke

BackgroundLung cancer and stroke share smoking as a major cause of disease. We investigated prevalence and risk of occult lung cancer with manifestation during the first year after stroke.MethodsAll patients >40 years of age with incident stroke in Denmark 2003–2015 were identified through the Danish Stroke Registry (n=85,893) and matched 1:10 on age and sex to the Danish background population without a history of stroke (n=858,740). Linking data to the Danish Cancer Registry we determined prevalence of occult primary lung cancer defined as the event of previously unknown lung cancer during a one-year follow-up in the stroke and the background population. Cox regression models with adjustments for demographics, co-morbidities and stroke risk factors were used to study risk compared to the background population.ResultsPrevalence (per 1000 person-years) of occult lung cancer in the stroke cohort was 5.3; in the background cohort 2.6. Prevalence separately for current smokers (n=26,055) was 9.6; ex-smokers (n=20,035) 6.5; never-smokers (n=27,268) 1.4. Risk of occult lung cancer (adjusted) was increased HR 1.95 in the stroke population. In the stroke population adjusting for stroke risk factors age (HR 1.24 per 10 years) and smoking (HR 7.1 in current smokers; HR 1.6 in ex-smokers) were the only significant risk factors for occult lung cancer.ConclusionsOccult lung cancer is rarely found in stroke patients who have never smoked. It is not uncommon in smokers in whom 1% of current smokers had occult lung cancer that became manifest within the first year after stroke.     

Stroke incidence and risk factors for stroke in Copenhagen, Denmark

Stroke incidence in Copenhagen, Denmark was recorded in a random population sample of 19,327 persons invited for two health examinations with 5 years' interval from 1976 to 1983. Stroke incidence increased exponentially with age. After adjustment to the age and sex distribution of the Danish population in 1980, the estimated incidence of first stroke was 1.41/1000 women and 2.48/1000 men; the total incidence was 1.94/1000 population. Risk factor analysis was based on the initial examination of 13,088 persons greater than 35 years old without previous stroke who responded to the first invitation, in whom 295 first strokes were subsequently observed. We used the regression model of Cox. However, our use of this model differs from the somewhat automatic procedures normally used to develop prognostic models. Evaluation of the causative effect of a particular risk factor requires that the direction of mutual influences between the factor in question and other risk factors is established/postulated. Among the 16 potential risk factors for stroke we examined, significant effects were found for age, sex, household income, smoking habits, systolic blood pressure, diabetes, plasma cholesterol concentration, ischemic heart disease, and atrial fibrillation. No significant effect could be demonstrated for a positive family history of stroke, years of school education, marital status, alcohol consumption, daily use of tranquilizers, body mass index, or postmenopausal hormone treatment.     

Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal

INTRODUCTION: Patients with nonvalvular atrial fibrillation are at increased risk for systemic embolism, predominantly disabling stroke. To study how stroke and mortality rates vary with different degrees of anticoagulation reflected by the international normalised ratio (INR) we critically assess information from different sources. MATERIALS AND METHODS: 1. Computerized search of the medical literature published between 1980 and July 2004 was performed using MEDLINE applied to various combinations of the search terms of atrial fibrillation, warfarin, anticoagulation, anticoagulation intensity, and INR, not restricted by language. 2. We performed a record linkage analysis with death hazard estimated as a continuous function of INR based on 21,967 patients. Similarly the risk of admission to hospital or death due to diseases of the vessels of the brain was estimated. 3. Re-analysis of data earlier published by Hylek et al. from year 2003.RESULTS AND CONCLUSIONS: 1. One randomised study showed a significantly lower risk of stroke for mean INR 2.4 compared to mean INR 1.3 combined with aspirin. Remaining studies found INRs of 2-2.5 to be as efficacious as higher anticoagulation intensities.2. Mortality as well as risk of admission to hospital or death due to diseases of the vessels of the brain followed U-shaped curves with minimum at INR 2.2 and 2.4, respectively. At high INR the risk increased 2.3 times per 1 unit increase of INR for death and 1.7 times for events in the vessels of the brain.3. The re-analysing of data of Hylek et al. indicated that there might be a substantial increase of the risk of intracranial hemorrhage when INR is increased from 2.5 to 4.We conclude that INRs in the interval 2.0--2.5 give the lowest risk of stroke and death in patients with nonvalvular atrial fibrillation.     

Low-dose warfarin in atrial fibrillation leads to more thromboembolic events without reducing major bleeding when compared to adjusted-dose--a meta-analysis

The use of warfarin with a range INR of 2.0-3.0 is recommended in prevention of stroke for nonvalvular atrial fibrillation (AF) patients, in particular those older than 75 years. The risk of bleeding that is associated with this range of INR has led to evaluate lower ranges (low-dose or fixed minidose) in terms of risks and benefits. A meta-analysis of all randomized controlled trials evaluating 'low-intensity' 'minidose' or 'low-dose anticoagulant' treatment for prevention of thromboembolic events in AF was conducted by two independent reviewers. Study quality was evaluated in a blinded fashion. Four original studies were retrieved. Outcome events were determined in various treatment groups: ischemic stroke, systemic embolism, thromboses (ischemic stroke, systemic embolism or myocardial infarction), vascular death, major hemorrhage and hemorrhagic death. Results obtained with a random effects model were expressed as a common relative risk. Adjusted-dose warfarin compared with lower dose warfarin (INR < or = 1.6) in 2108 randomised patients significantly reduced the risk of any thrombosis: Relative risk (RR): 0.50 (95% CI; 0.25 to 0.97). The RR was 0.46 (95%CI; 0.2 to 1.07) for ischemic stroke. Inversely lower dose did not statistically decrease the risk for major hemorrhage compared to adjusted-dose: RR adjusted-dose vs lower dose: 1.23 (95% CI; 0.67-2.27). The RR was 0.97 (95 % CI 0.27-3.54) for hemorrhagic death. Our meta-analysis showed that adjusted-dose compared with low-dose or minidose warfarin therapy (INR < or =1.6) was more effective to prevent ischemic thromboembolic events in patients with atrial fibrillation.     

Secondary prevention in non-valvular atrial fibrillation patients: a practical approach with edoxaban

Patients with atrial fibrillation and prior stroke or transient ischemic attack exhibit a very high risk of recurrence. Secondary prevention with oral anticoagulants is mandatory. Overall, clinical guidelines recommend the use of target-specific oral anticoagulants over vitamin K antagonists for secondary prevention of stroke in patients with atrial fibrillation. However, many patients with atrial fibrillation and previous stroke are not receiving the appropriate antithrombotic treatment, perhaps due to the perceived risks of anticoagulation including the risk of hemorrhagic transformation of an ischemic stroke. The ENGAGE AF-TIMI 48 trial showed that although edoxaban 60 mg and warfarin reduced the risk of stroke to a similar extent, edoxaban exhibited a lesser risk of bleeding, particularly intracranial hemorrhage. Importantly, these data were independent of the presence of prior stroke or transient ischemic attack. Therefore, edoxaban can be used in both primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. The aim of this review was to update the available evidence about edoxaban in the clinical management of secondary prevention in individuals with non-valvular atrial fibrillation.     

Heparin in acute stroke with atrial fibrillation: clinical relevance of very early treatment.

BACKGROUND: The risk-benefit ratio of early vs late heparinization for acute stroke with nonvalvular atrial fibrillation remains unsettled. OBJECTIVE: To clarify the relationship between timing to heparinization and functional outcome in acute cardioembolic stroke. DESIGN: Consecutive case series. SETTING: Referral center. PATIENTS: In 231 patients with stroke and nonvalvular atrial fibrillation, intravenous or subcutaneous heparin administered with the goal of achieving an activated partial thromboplastin time (APTT) 1.5 to 2.0 times control values. Delay to the initiation of heparin therapy was less than 6 hours from the onset of symptoms in 74 patients and between 6 and 48 hours in 157 patients. Functional outcome (Rankin scale) was assessed 9 +/- 3 (mean +/- SD) days from stroke onset using multivariate analysis and including in the model treatment delay, risk factors (eg, age, hypertension, diabetes, hypercholesterolemia, previous stroke, and heart disease), initial neurological severity, and baseline computed tomographic findings (eg, early signs of infarction and white matter abnormalities). Clinical symptoms on admission (Mathew score) and baseline radiological findings were evaluated in all subjects. The bleeding rate was assessed on subsequent computed tomographic (CT) scans (obtained 7 +/- 2 days after stroke). The relationship between APTT ratios and stroke recurrence or hemorrhagic worsening was also tested. MAIN OUTCOME MEASURES: Functional outcome at hospital discharge and incidence of early recurrent strokes and bleeding complications. RESULTS: Mortality (9%), hemorrhagic worsening (3.4%), and early stroke recurrence (2.1%) occurred in the hospital. Complete recovery was associated with age younger than 70 years (odds ratio [OR], 0.21; 95% confidence interval [CI], 0.05-0.70), a baseline Mathew score higher than 74 (OR, 11.5; 95% CI, 4.95-26.70), normal baseline CT findings (OR, 8.86; CI, 3.99-19.60), and early heparinization (OR, 1.7; 95% CI, 1.10-2.50). Targeted APTT ratios were achieved at 24 hours in fewer than 50% of patients. Whereas stroke recurrence was associated with lower mean APTT ratios, higher mean APTT ratios were observed in patients with symptomatic bleeding, especially on the day of bleeding. Age, admission stroke severity, blood pressure, and baseline CT findings did not predict hemorrhagic worsening. CONCLUSIONS: Delaying anticoagulation in alert patients with stroke and nonvalvular atrial fibrillation is not endorsed by the initial severity of symptoms or the early signs of infarction on CT scan. Functional recovery is improved the sooner heparin is administered. These findings suggest that heparin also has therapeutic properties. However, close APTT monitoring is warranted to lessen the incidence of untoward complications.