Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

BACKGROUND: Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. METHODS/DESIGN: The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. CONCLUSION: The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design are combined with the strengths of a national clinical quality register in allowing simplified enrolment and follow-up of study patients. In addition, the register adds the possibility of directly assessing the external validity of the study findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02961348 . Registered on 8 November 2016.

To Treat or Not to Treat: Anticoagulants as Secondary Preventives to the Oldest Old With Atrial Fibrillation.

BACKGROUND AND PURPOSE: Anticoagulant treatment is effective for preventing recurrent ischemic strokes in patients who have atrial fibrillation. This benefit is paid by a small increase of hemorrhages. Anticoagulant-related hemorrhages seem to increase with age, but there are few studies showing whether the benefits of treatment persist in old age. METHODS: For this observational study, 4 different registers were used, among them Riksstroke, the Swedish Stroke Register. Patients who have had a recent ischemic stroke, were 80 to 100 years of age, and had atrial fibrillation, were included from 2006 through 2013. The patients were stratified into 3 age groups: 80 to 84, 85 to 89, and ≥90 years of age. Information on stroke severity, risk factors, drugs, and comorbidities was gathered from the registers. The patients were followed with respect to ischemic or hemorrhagic stroke, other hemorrhages, or death. RESULTS: Of all 23 356 patients with atrial fibrillation, 6361 (27%) used anticoagulants after an ischemic stroke. Anticoagulant treatment was associated with less recurrent ischemic stroke in all age groups. Hemorrhages increased most in the ≥90-year age group, but this did not offset the overall beneficial effect of the anticoagulant. Apart from age, no other cardiovascular risk factor or comorbidity was identified that influenced the risk of anticoagulant-associated hemorrhage. Drugs other than anticoagulants did not influence the incidence of major hemorrhage. CONCLUSIONS: Given the patient characteristics in this study, there is room for more patients to be treated with anticoagulants, without hemorrhages to prevail. In nonagenarians, hemorrhages increased somewhat more, but this did not affect the overall outcome in this age stratum.

[Anticoagulants after acute ischemic stroke with atrial fibrillation]. / Antikoagulantia efter akut ischemisk stroke med förmaksflimmer - Frågan om rätt tidpunkt för insättning kräver randomiserad klinisk prövning.

Early or delayed onset of oral anticoagulant therapy in patients with acute ischemic stroke with atrial fibrillation is an unsolved issue. Retrospectively, 294 patient records at two hospitals were scrutinized according to a protocol consisting of 20 items regarding choice of therapy (warfarin or NOAC), time for onset of therapy, CT findings of bleeding, capacity to swallow, and occurrence of clinical deterioration during the acute phase. Out of 249 patients who survived the acute phase, 116 (47%) patients were given a new prescription of warfarin or NOAC at discharge, while 43 (17 %) continued with anticoagulant therapy already prescribed before the onset of stroke. The median value for new prescriptions in relation to stroke admission was 5 days. The pattern was similar for warfarin and NOAC. Patients in whom anticoagulant therapy was started early were characterized by good capacity to swallow and no signs of bleeding on initial CT. The question ¼early or delayed onset of oral anticoagulant therapy after acute ischemic stroke with atrial fibrillation« needs to be tested in a randomized clinical trial.

Effects of candesartan in acute stroke on vascular events during long-term follow-up: results from the Scandinavian Candesartan Acute Stroke Trial (SCAST).

BACKGROUND: Randomized-controlled trials have shown no beneficial short-term effects of blood pressure lowering treatment in the acute phase of stroke. AIM: We aimed to see whether blood pressure lowering treatment with candesartan in the acute phase can lead to benefits that become apparent over a longer period of follow-up. METHODS: The Scandinavian Candesartan Acute Stoke Trial was a randomized- and placebo-controlled trial of candesartan in 2,029 patients with acute stroke and systolic blood pressure ≥140 mmHg. Trial treatment was given for seven-days, and the primary follow-up period was six-months. We have used the national patient registries and the cause of death registries in the Scandinavian countries to collect data on vascular events and deaths up to three-years from randomization. The primary end-point was the composite of stroke, myocardial infarction, or vascular death, and we used Cox proportional hazards regression model for analysis. RESULTS: Long-term data were available for 1,256 of the 1,286 patients (98%) from Scandinavia. The risk of the primary composite end-point did not differ significantly between the groups (candesartan 178/632 events, placebo 203/624 events, hazard ratio = 0·87, 95% confidence interval 0·71-1·07). There were also no statistically significant differences for the secondary end-points stroke and all-cause death, or in any of the pre-specified subgroups. CONCLUSIONS: Treatment with candesartan in the acute phase of stroke was not associated with clear long-term clinical benefits. This result supports the conclusion from trials with short-term follow-up, that blood pressure lowering treatment with candesartan should not be given routinely to patients with acute stroke and raised blood pressure.

Benefit of anticoagulation unlikely in patients with atrial fibrillation and a CHA2DS2-VASc score of 1.

BACKGROUND: Patients with atrial fibrillation (AF) and ≥1 point on the stroke risk scheme CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) are considered at increased risk for future stroke, but the risk associated with a score of 1 differs markedly between studies. OBJECTIVES: The goal of this study was to assess AF-related stroke risk among patients with a score of 1 on the CHA2DS2-VASc. METHODS: We conducted this retrospective study of 140,420 patients with AF in Swedish nationwide health registries on the basis of varying definitions of "stroke events." RESULTS: Using a wide "stroke" diagnosis (including hospital discharge diagnoses of ischemic stroke as well as unspecified stroke, transient ischemic attack, and pulmonary embolism) yielded a 44% higher annual risk than if only ischemic strokes were counted. Including stroke events in conjunction with the index hospitalization for AF doubled the long-term risk beyond the first 4 weeks. For women, annual stroke rates varied between 0.1% and 0.2% depending on which event definition was used; for men, the corresponding rates were 0.5% and 0.7%. CONCLUSIONS: The risk of ischemic stroke in patients with AF and a CHA2DS2-VASc score of 1 seems to be lower than previously reported.

High prevalence of atrial fibrillation among patients with ischemic stroke.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a common cause of devastating but potentially preventable stroke. Estimates of the prevalence of AF among patients with stroke vary considerably because of difficulties in detection of intermittent, silent AF. Better recognition of AF in this patient group may help to identify and offer protection to individuals at risk. Our aim was to determine the nationwide prevalence of AF among patients with ischemic stroke, as well as their use of oral anticoagulation. METHODS: Cross-sectional study of unselected patients in cross-linked nationwide Swedish health registers. All 94 083 patients with a diagnosis of ischemic stroke in the nationwide stroke register Riks-Stroke between 2005 and 2010 were studied. Information about previously diagnosed AF, and comorbidity, was obtained from the nationwide Patient Register and cross-referenced with the national Drug Register containing data on all dispensed pharmacological prescriptions in Sweden. RESULTS: Combination of data from Riks-Stroke and from the Patient Register showed that 31 428 (33.4%) patients with ischemic stroke had previously known, or newly diagnosed, AF. Of those, only 16.2% had received warfarin in a pharmacy within 6 months before stroke onset. After hospital discharge, only 35.0% of the survivors received warfarin within the first 3 months after discharge. The likelihood for underlying AF was strongly correlated to the CHA2DS2-VASC score, which is a point based scheme for assessment of stroke risk in AF but which also predicts likelihood of AF. In this scheme points are given for age, previous stroke or transient ischemic attack, hypertension, heart failure, diabetes, vascular disease and female sex. CONCLUSIONS: Access to nationwide register data shows that AF is more common among patients with ischemic stroke than those previously reported. Few patients with stroke and AF had anticoagulant treatment before the event, and few got it after the event. CHA2DS2-VASc could be a useful monitoring tool to intensify efforts to diagnose AF among patients with cryptogenic stroke.

Warfarin-associated intracerebral hemorrhage after ischemic stroke.

BACKGROUND AND PURPOSE: The aim was to investigate the risk of intracerebral hemorrhage (ICH) in patients with ischemic stroke taking warfarin and whether this risk changed over time. METHODS: Between 2001 and 2008, the Swedish Stroke Register registered 12,790 patients with ischemic stroke discharged on warfarin. The patients was studied in two 4-year periods (inclusion 2001-2004: follow-up until 2005 and inclusion 2005-2008: follow-up until 2009) for which rates of subsequent ICH were calculated. Adjusted hazard ratios, comparing the second period with the first period, were estimated in Cox regression models. RESULTS: Of 6039 patients, 58 patients (1.0%) in the first period and 69 of 6751 patients (1.0%) in the second period had subsequent ICH. Annual rates of ICH ranged from 0.37% in the first period to 0.39% in the second period (adjusted hazard ratio, 1.04; 95% confidence interval, 0.73-1.48). CONCLUSIONS: In this nationwide study, the risk of warfarin-associated ICH among ischemic stroke patients was low and did not change during the 2000s.

Trends in stroke treatment and outcome between 1995 and 2010: observations from Riks-Stroke, the Swedish stroke register.

BACKGROUND: Continuous changes in stroke treatment and care, as well as changes in stroke characteristics, may alter stroke outcome over time. The aim of this paper is to describe time trends for treatment and outcome data, and to discuss if any such changes could be attributed to quality changes in stroke care. METHODS: Data from Riks-Stroke, the Swedish stroke register, were analyzed for the time period of 1995 through 2010. The total number of patients included was 320,181. The following parameters were included: use of computed tomography (CT), stroke unit care, thrombolysis, medication before and after the stroke, length of stay in hospital, and discharge destination. Three months after stroke, data regarding walking, toileting and dressing ability, as well social situation, were gathered. Survival status after 7, 27 and 90 days was registered. RESULTS: In 1995, 53.9% of stroke patients were treated in stroke units. In 2010 this proportion had increased to 87.5%. Fewer patients were discharged to geriatric or rehabilitation departments in later years (23.6% in 2001 compared with 13.4% in 2010), but more were discharged directly home (44.2 vs. 52.4%) or home with home rehabilitation (0 vs. 10.7%). The need for home help service increased from 18.2% in 1995 to 22.1% in 2010. Regarding prevention, more patients were on warfarin, antihypertensives and statins both before and after the stroke. The functional outcome measures after 3 months did improve from 2001 to 2010. In 2001, 83.8% of patients were walking independently, while 85.6% were independent in 2010. For toileting, independence increased from 81.2 to 84.1%, and for dressing from 78.0 to 80.4%. Case fatality (CF) rates after 3 months increased from 18.7% (2001) to 20.0% (2010). This trend is driven by patients with severe strokes. CONCLUSIONS: Stroke outcomes may change over a relatively short time period. In some ways, the quality of care has improved. More stroke patients have CT, more patients are treated in stroke units and more have secondary prevention. Patients with milder strokes may have benefited more from these measures than patients with severe strokes. Increased CF rates for patients with severe stroke may be caused by shorter hospital stays, shorter in-hospital rehabilitation periods and lack of suitable care after discharge from hospital.

Reduced risk of death with warfarin - results of an observational nationwide study of 20 442 patients with atrial fibrillation and ischaemic stroke.

BACKGROUND: Warfarin is demonstrated to be superior in efficacy over antiplatelet agents for the prevention of stroke, but the relationship between warfarin and mortality is less clear. Our aim was to investigate this relationship in a large cohort of unselected patients with atrial fibrillation and ischaemic stroke. METHODS: This observational study was based on patients who were discharged alive and registered in the Swedish Stroke Register in 2001 through 2005. Vital status was retrieved by linkage to the Swedish Cause of Death Register. We calculated a propensity score for the likelihood of warfarin prescription at discharge from hospital. The risk of death and 95% confidence intervals were estimated in Cox regression models. RESULTS: Out of the 20 442 patients with atrial fibrillation and ischaemic stroke (mean age = 79·5 years), 31% (n = 6399) were prescribed warfarin. After adjustment for the propensity score, warfarin was associated with a reduced risk of death (0·67; 95% confidence interval, 0·63-0·71). The crude rate (per 100 person-years) of fatal non-haemorrhagic stroke was lower in patients who received warfarin (1·60; 95% confidence interval, 1·34-1·89) compared to those who received antiplatelet (6·83; 95% confidence interval, 6·42-7·25). The rates (per 100 person-years) of fatal haemorrhagic stroke were 0·21 (95% confidence interval, 0·12-0·32) and 0·43 (95% confidence interval, 0·34-0·55) in patients prescribed warfarin and antiplatelet therapy, respectively. CONCLUSIONS: In addition to its established benefit for stroke prevention, warfarin therapy in patients with atrial fibrillation and ischaemic stroke was associated with a reduced risk of death, without an increased risk of fatal haemorrhagic stroke.

Hemorrhage after ischemic stroke - relation to age and previous hemorrhage in a nationwide cohort of 58,868 patients.

BACKGROUND: In randomized controlled trials of secondary prevention after stroke, the risk of hemorrhage varies between 1% and 5% per year in patients with antithrombotic therapy, i.e. anticoagulants and antiplatelets. AIM: To explore the rate and the risk of hemorrhage after stroke in a nationwide cohort. METHODS: We identified 58 868 first ever ischemic stroke patients in the Swedish Stroke Register during 2001 to 2005 (=index stroke) and followed them by record linkage to the National Patient Register. Rates of hemorrhage and hazard ratios, for comparisons of rates between subgroups, were calculated. RESULTS: Of the 58 586 ischemic stroke patients identified, 5527 (9·4%) had a history of hemorrhage. During follow-up (mean 2·0 years), 2876 patients endured a hemorrhage, giving an average hemorrhage rate of 2·6 (95% confidence interval 2·5-2·7) per 100 person-years. After index stroke, 11% of the patients were discharged with anticoagulants, and 79% with antiplatelets. Given the differences in baseline characteristics, the hemorrhage rates (per 100 person-years) were 2·5 (95% confidence interval 2·2-2·8), 2·4 (95% confidence interval 2·3-2·5), and 3·8 (95% confidence interval 3·5-4·2) in patients prescribed anticoagulants, antiplatelets, and no antithrombotics, respectively. There was an increased risk of hemorrhage in patients ≥75 years compared with those <75 years (hazard ratio = 1·61, 95% confidence interval 1·49-1·73) and in patients with previous hemorrhages compared with those without (hazard ratio = 1·82, 95% confidence interval 1·64-2·02). CONCLUSIONS: When antithrombotics were used in large-scale clinical practice, the observed rates of hemorrhage were similar with anticoagulant therapy but increased with antiplatelet therapy compared with rates reported in randomized controlled trials. Old age and previous hemorrhage were associated with an increased risk of hemorrhage after an ischemic stroke.

Comparison of cardiovascular risk factors and survival in patients with ischemic or hemorrhagic stroke.

BACKGROUND: Differences in risk factor profiles between patients with ischemic and hemorrhagic stroke may have an impact on subsequent mortality. AIM: To explore cardiovascular disease risk factors, including the CHADS(2) score, with survival after ischemic or hemorrhagic stroke. METHODS: Between 2001 and 2005, 87 111 (83%) ischemic stroke, 12 497 (12%) hemorrhagic stroke, and 5435 (5%) patients with unspecified stroke were identified in the Swedish Stroke Register. Data on gender, age, and cardiovascular disease risk factors were linked to the Swedish Hospital Discharge and Cause of Death Registers. Adjusted odds and hazard ratios and 95% confidence interval were calculated using logistic and Cox proportional hazard regression models. RESULTS: Hemorrhagic stroke patients were younger than ischemic stroke patients. All cardiovascular disease risk factors studied, alone or combined in the CHADS(2) score, were associated with higher odds ratios for ischemic stroke vs. hemorrhagic stroke. Higher CHADS(2) scores and all studied risk factors except hypertension were associated with higher odds ratio for death by ischemic stroke than hemorrhagic stroke. Ischemic stroke was associated with lower early mortality (within 30 days) vs. hemorrhagic stroke (hazard ratio = 0·28, confidence interval 0·27 to 0·29). CONCLUSIONS: Patients with hemorrhagic stroke had a higher risk of dying within the first 30 days after stroke, but the risk of death was similar in the two groups after one-month. Hypertension was the only cardiovascular disease risk factor associated with an increased mortality rate for hemorrhagic stroke as compared to ischemic stroke.

First-ever atrial fibrillation documented after hemorrhagic or ischemic stroke: the role of the CHADS(2) score at the time of stroke.

BACKGROUND: The CHADS(2) score (C, congestive heart failure [CHF]; H, hypertension [HT]; A, age ≥75 y; D, diabetes mellitus; S(2) , prior stroke or transient ischemic attack) is used to assess the risk of ischemic stroke in patients with atrial fibrillation (AF). However, its role in patients without documented AF is not well explored. HYPOTHESIS: The goal of the current study was to explore if the incidence of hospitalization with first-ever AF after stroke increased with increasing CHADS(2) score. METHODS: We identified 57636 patients with nonfatal stroke and no documented AF in the Swedish Stroke Register (Riks-Stroke) during 2001-2004 and followed them for a mean of 2.2 years through record linkage to the Inpatient and Cause of Death registers. Cox regression hazard models were used to estimate the relative risk (RR) of new AF following stroke and its association with different CHADS(2) scores. RESULTS: Overall, 2769 patients were hospitalized with new AF (4.8%, 21.7 per 1000 person-years). The incidence increased from 9.6 per 1000 person-years in CHADS(2) score 0 to 42.7 in CHADS(2) score 6, conferring a RR of 4.2 (95% confidence interval [CI]: 2.5-6.8). For CHADS(2) scores 3-5, the RRs were approximately 3 (vs CHADS(2) score 0). Adjusted RRs were 1.9 (95% CI: 1.7-2.1) for CHF, 1.4 (95% CI: 1.3-1.5) for HT, 2.1 (95% CI: 2.0-2.3) for age ≥75 years, 0.9 (95% CI: 0.8-1.0) for diabetes, and 1.0 (95% CI: 0.91-1.07) for previous stroke. The risk of AF was higher in ischemic than in hemorrhagic stroke. CONCLUSIONS: In this retrospective register study, the incidence of AF following stroke was strongly influenced by higher CHADS(2) scores where age ≥75 years, CHF, and HT were the contributing CHADS(2) components.

The Riks-Stroke story: building a sustainable national register for quality assessment of stroke care.

BACKGROUND: Riks-Stroke, the Swedish Stroke Register, is the world's longest-running national stroke quality register (established in 1994) and includes all 76 hospitals in Sweden admitting acute stroke patients. The development and maintenance of this sustainable national register is described. METHODS: Riks-Stroke includes information on the quality of care during the acute phase, rehabilitation and secondary prevention of stroke, as well as data on community support. Riks-Stroke is unique among stroke quality registers in that patients are followed during the first year after stroke. The data collected describe processes, and medical and patient-reported outcome measurements. The register embraces most of the dimensions of health-care quality (evidence-based, safe, provided in time, distributed fairly and patient oriented). RESULT: Annually, approximately 25,000 patients are included. In 2009, approximately 320,000 patients had been accumulated (mean age 76-years). The register is estimated to cover 82% of all stroke patients treated in Swedish hospitals. Among critical issues when building a national stroke quality register, the delicate balance between simplicity and comprehensiveness is emphasised. Future developments include direct transfer of data from digital medical records to Riks-Stroke and comprehensive strategies to use the information collected to rapidly implement new evidence-based techniques and to eliminate outdated methods in stroke care. CONCLUSIONS: It is possible to establish a sustainable quality register for stroke at the national level covering all hospitals admitting acute stroke patients. Riks-Stroke is fulfilling its main goals to support continuous quality improvement of Swedish stroke services and serve as an instrument for following up national stroke guidelines.

The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial.

BACKGROUND: Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. METHODS: Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered, number NCT00120003 (ClinicalTrials.gov), and ISRCTN13643354. FINDINGS: 2029 patients were randomly allocated to treatment groups (1017 candesartan, 1012 placebo), and data for status at 6 months were available for 2004 patients (99%; 1000 candesartan, 1004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg [SD 23/14] in the candesartan group on day 7 vs 152/84 mm Hg [22/14] in the placebo group; p<0·0001). During 6 months' follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events, vs placebo, 111 events; adjusted hazard ratio 1·09, 95% CI 0·84-1·41; p=0·52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1·17, 95% CI 1·00-1·38; p=0·048 [not significant at p≤0·025 level]). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo. INTERPRETATION: There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect. FUNDING: South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.

Discarding heparins as treatment for progressive stroke in Sweden 2001 to 2008.

BACKGROUND AND PURPOSE: High-dose heparin has been used extensively to treat patients with progressive ischemic stroke, but the scientific support is poor and the current stroke guidelines advise against its use. We studied how heparin treatment for progressive stroke has been discarded in Sweden. METHODS: All 78 hospitals in Sweden that admit acute stroke patients participate in Riks-Stroke, the Swedish Stroke Register. During 2001 to 2008, information on the use of high-dose heparin was available for 155,344 patients with acute ischemic stroke. The determinants as to region, patient characteristics, and stroke service settings were analyzed. RESULTS: Use of heparin for progressive stroke declined from 7.5% (2001) to 1.6% (2008) of all patients with ischemic stroke. The marked regional differences present in 2001 were reduced over time. The use of heparin declined at a similar rate in all types of hospital settings, in stroke units vs nonstroke units, and in neurological vs medical wards. Independent predictors of use of heparin included younger age, first-ever stroke, independence in activities of daily living before stroke, atrial fibrillation, no aspirin treatment, and lowered consciousness on admission. CONCLUSIONS: There is no immediate, stepwise effect of new scientific information and national guidelines on clinical practice. Rather, the phasing out of heparin has followed a linear course over several years, with less variation between hospitals. We speculate that open comparisons between hospitals in a national stroke register may have helped to reduce the variations in clinical practice.