Lower Risk Of Recurrent Stroke Research Articles

Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial.

To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation. Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex. In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women. ARISTOTLE ClinicalTrials.gov number, NCT00412984.

Seven-year follow-up of percutaneous closure of patent foramen ovale

BackgroundObservational studies favor percutaneous closure of patent foramen ovale (PFO) over medical treatment to reduce recurrent stroke while randomized trials fail to demonstrate significant superiority of percutaneous PFO closure. Few long-term studies are available post PFO closure. This study reports long-term clinical outcomes after percutaneous PFO closure. MethodsBetween 1997 and 2006, 86 consecutive eligible patients with cerebrovascular events, presumably related to PFO, underwent percutaneous PFO closure. All 86 patients were invited to a long-term follow-up, which was carried out during 2011 and 2012. ResultsPercutaneous PFO closure was successfully performed in 85 of 86 patients. The follow-up rate was 100%. No cardiovascular or cerebrovascular deaths occurred. Two patients (both women) died from lung cancer during follow-up. Follow-up visits were conducted for 64 patients and the remaining 20 patients were followed up by phone. The mean follow-up time was 7.3years (5 to 12.4years). Mean age at PFO closure was 49years. One patient had a minor stroke one month after PFO closure and a transient ischemic attack (TIA) two years afterwards. One other patient suffered from a TIA six years after closure. No long-term device-related complications were observed. ConclusionsPercutaneous PFO closure was associated with very low risk of recurrent stroke and is suitable in most patients. We observed no mortality and no long-term device-related complications related to PFO closure, indicating that percutaneous PFO closure is a safe and efficient treatment even in the long term.

Abstract 197: Do the CHADS 2 , CHA 2 DS 2 -VASc and HAS-BLED Scores Predict Recurrent Stroke and GI Bleeding in Patients with Acute Ischemic Stroke or TIA and Atrial Fibrillation?

Background: In patients with atrial fibrillation (AF) the CHADS 2 and CHA 2 DS 2 -VASc score are used to provide a risk for subsequent stroke and the HAS-BLED score for hemorrhage. These scores were derived from large cohorts of patients with AF, however, only 8 - 25% of the patients had a past history of stroke. We wanted to determine whether these prediction scores had utility in patients with AF who have had a recent stroke or TIA. Methods: We selected patients with AF and a first stroke or TIA from the 2002-3, 2004-5, 2008-9 and 2010-11 Ontario Stroke Audits (OSA). The OSA includes data from a simple random sample of 15 - 20% of stroke and TIA patients presenting to all Ontario hospitals identified using ICD-10 diagnostic codes I60, I61, I63, I64, H34.1 and G45. Recurrent ischemic stroke, hemorrhagic stroke and major GI hemorrhage were obtained by linking the OSA data to administrative databases for hospital admissions in the subsequent year. Results: There were 3,960 patients with AF in the OSA who were discharged alive following their first acute stroke or TIA. The median age was 80. At discharge 41% of the patients were prescribed anticoagulants, 24% antiplatelet therapy, 25% both and 9% were prescribed no antithrombotic therapy. The one year readmission rate for stroke was 5.3% (including 0.4% hemorrhagic stroke) and 1.9% for major hemorrhage. Multivariable logistic regression models did not show any significant association between the CHADS 2 and CHA 2 DS 2 -VASc scores and the risk of recurrent stroke. The HAS-BLED score failed to predict hemorrhagic stroke or major bleeding and the risk of major bleeding for the entire group at one year was low (1.9%). Patients prescribed anticoagulants at discharge had fewer recurrent strokes (OR 0.55; 95% CI 0.34 - 0.90, p=0.02), a lower one year mortality (OR 0.42; 95% CI 0.31 - 0.56, p &lt;0.001) and the same risk of major bleeding as compared to patients not receiving anticoagulants. Conclusions: The CHADS 2 , CHA 2 DS 2 -VASc and HAS-BLED scores did not predict recurrent stroke or hemorrhage in patients following an acute stroke or TIA. Anticoagulation at discharge was associated with a lower risk of recurrent stroke and death without a significant increase in the risk of major hemorrhage.

Abstract 2292: Dipyridamole Induced Headache Indicates Lower Recurrence Risk in Secondary Prevention of Ischemic Stroke

Background Headache is a common adverse event in patients treated with dipyridamole (DP) for secondary stroke prevention. The headache resembles migraine, possibly indicating that vessel walls and endothelium of cerebral vessels are still intact and able to dilate. Purpose We hypothesized that patients who develop headache on DP will have a lower risk of recurrent stroke compared to patients without headache. Methods We analysed data from PROFESS (N=20,332) comparing aspirin plus DP with clopidogrel. Prospective data on headache as an adverse event within 7 days of start of medication or reason for discontinuation of study drug and recurrent stroke incidence were collected. We compared the relative risk of recurrent stroke in patients who did and did not get headache and who did or did not discontinue study medication due to headache. Analyses were repeated in the smaller ESPS 2 study (N=6,602) investigating aspirin, aspirin plus DP, DP or placebo in secondary stroke prevention. Results In PROFESS 3067 patients taking aspirin plus DP complained of headache in the first 7 days while 6988 did not. In the aspirin plus DP group, the recurrent stroke risk after 2.5 years was 8.2% in patients with and 9.4% in patients without headache resulting in a RR of 0.90 (95% CI 0.81-1.01, p= 0.07). In the clopidogrel treated group there was no difference in stroke risk between patients with and without headache RR = 1.00 (95% CI 0.82-1.23). In PROFESS, 518 patients taking aspirin plus DP discontinued treatment due to headache in the first 90 days. Their risk of recurrent stroke was 5.0%. In patients who did not discontinue aspirin plus DP due to headache in the first 90 days, the recurrent stroke risk was 9.2% resulting in a RR of 0.53 (95% CI 0.36-0.79, p=0.001). In the clopidogrel treated patients the RR was 0.89(95% CI 0.36-2.20); 7.9% of 63 clopidogrel patients who discontinued due to headache within 90 days of randomization had stroke vs. 8.9% in all other patients. In ESPS 2, 129 patients taking aspirin plus DP discontinued treatment due to headache in the first 90 days. Their rate of recurrent stroke was 6.2%. In patients who did not discontinue aspirin plus DP due to headache in the first 90 days, the recurrent stroke rate was 9.8% resulting in a RR of 0.63 (95% CI 0.31-1.26, p=0.18). Conclusions In PROFESS patients who developed headache on aspirin plus DP for secondary stroke prevention had a reduced risk of stroke recurrence in comparison with those who did not or were treated with clopidogrel. These results are directionally supported by similar but non-significant findings on treatment discontinuation of aspirin plus DP in ESPS 2. Headache in clopidogrel treated patients did not demonstrate any protective effects, suggesting specificity. These results suggest that DP-induced headache may be a marker for more reactive vessel walls in cerebral arteries.

Abstract 2668: Lacunar Strokes In Patients With Symptomatic Intracranial Stenosis

Background and Purpose: Lacunar strokes are conventionally attributed to a distinct microvascular pathophysiology, but the “lacunar hypothesis” has been challenged since some small deep infarcts are identified in patients with sources of cardioembolism or large vessel atherosclerotic disease. We hypothesized that patients with intracranial stenosis with a lacunar stroke presentation would have a lower risk of recurrent stroke than those with an index non-lacunar stroke, and that their recurrent strokes would predominantly be lacunar. Methods: We analyzed subjects enrolled with an index stroke into the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. The index and endpoint strokes were classified as lacunar or non-lacunar by central adjudication. The primary endpoint was recurrent ischemic stroke. Cox proportional hazard models were generated with stratification for severity of stenosis. Results: 347 subjects were enrolled after an index stroke, 38 were lacunar and 309 were non-lacunar. Over a mean follow-up of 1.8 years there was no significant difference in stroke recurrence between patients whose index stroke was lacunar (7/38; 18%) vs. non-lacunar (69/309; 22%) (HR 0.79, 95%CI: 0.36-1.71). Further, no significant differences were found when groups were stratified by 50-69% stenosis (HR 0.50, 95%CI:0.12-2.1) and ≥70% stenosis (HR 0.87, 95%CI: 0.34-2.2) but power was limited. Of the 7 recurrent strokes in patients whose index stroke was lacunar, all 7 were non-lacunar and 3 were in the territory of the stenotic artery. Of the 69 recurrent strokes in patients whose index stroke was non-lacunar, 6 (9%) were lacunar of which 4 were in the territory of the stenotic artery. Conclusions: The risk of recurrent stroke due to intracranial stenosis was similar in patients who presented with lacunar vs. non-lacunar strokes, and all recurrent strokes in patients presenting with lacunar stroke were non-lacunar. These findings suggest that the pathophysiology of index and recurrent strokes in patients presenting with a lacunar stroke and intracranial stenosis is related to the stenosis and not microvascular disease. Therefore, patients with intracranial stenosis who present with lacunar strokes should be included in future trials investigating secondary stroke prevention for symptomatic intracranial stenosis.

Use of Secondary Medical Prophylaxis and Clinical Outcome Among Patients With Ischemic Stroke

Although secondary medical prevention strategies in patients with stroke are well established, only sparse data exist regarding their effectiveness in routine care. We examined the effectiveness in a nationwide, population-based follow-up study. Using data from the Danish National Indicator Project (DNIP), 28,612 patients hospitalized for ischemic stroke in 2003 to 2006 were identified. Information on drug use and outcomes was by individual-level record linkage with national medical databases. Hazard ratios were computed for death, myocardial infarction, and recurrent stroke according to drug use after hospital discharge. Treatment with antiplatelets, oral anticoagulants, antihypertensives, or statins was associated with a lower risk of the combined end point of death, myocardial infarction, or recurrent stroke during a mean follow-up period of 2.7 years (adjusted hazard ratios [HRs] from 0.44 [95% CI, 0.39-0.49] to 0.94 [95% CI, 0.89-0.99]). All drug classes were associated with lower risk of death (adjusted HRs from 0.36 [95% CI, 0.32-0.41] to 0.85 [95% CI, 0.80-0.90]), with oral anticoagulant treatment in patients with atrial fibrillation being particularly effective in elderly women (>80 years; adjusted HR, 0.35; 95% CI, 0.28-0.45). Oral anticoagulant treatment was associated with a lower risk of recurrent stroke (adjusted HR, 0.58; 95% CI, 0.47-0.73), and statins were associated with a lower risk of myocardial infarction (adjusted HR, 0.84; 95% CI, 0.73-0.97) and recurrent stroke (adjusted HR, 0.86; 95% CI, 0.79-0.92). Secondary medical prophylaxis after ischemic stroke was associated with improved outcome in routine settings. Although these findings are of an observational nature, they tend to support the results from previous randomized trials.

Antithrombotische und Antikoagulanzientherapie nach Schlaganfall und transitorisch ischämischer Attacke

Patients with a transient ischemic attack (TIA) or ischemic stroke are at high risk for a recurrent stroke. Platelet inhibitors can reduce this risk in patients with non-cardioembolic stroke or TIA. Aspirin is used for secondary prevention in patients with a low risk of recurrent stroke while the combination of aspirin and dipyridamole or clopidogrel is recommended in patients with a higher risk. Patients with atrial fibrillation have a five-fold increased risk of stroke. In comparison to placebo oral anticoagulation reduces the risk of stroke by 60-70% in primary and secondary stroke prevention. Aspirin can still reduce the relative stroke risk by 22% in patients with atrial fibrillation who have contraindications against anticoagulation. Given the limitations of oral anticoagulation with vitamin K antagonists a new generation of anticoagulants is currently being investigated which include factor Xa inhibitors and direct thrombin antagonists. Dabigatran has been shown to be as efficacious as warfarin given at a lower dose and significantly more efficacious when administered at a higher dosage. Both cerebral and intracranial hemorrhages were reduced by 60-80% in patients treated with dabigatran when compared to warfarin.

Recurrent Events in Transient Ischemic Attack and Minor Stroke

The risk of a recurrent stroke after transient ischemic attack (TIA) or minor stroke is high. Clinical trials are needed to assess acute treatment options in these patients. We sought to evaluate the type of recurrent events and to identify which subsets of patients are at risk for recurrent events. One hundred and eighty patients with TIA or minor stroke were examined within 12 hours and underwent brain MRI within 24 hours. Any neurological deterioration was recorded, and a combination of clinical and MRI factors were used to create a combined event classification. Subgroups of patients analyzed included classical TIA, patients with NIHSS=0, and patients with NIHSS >0 in ED. Overall there were 38 events in 36 patients (20% event rate); 20 were symptomatic and 18 were silent (only evident because of the follow up MRI). 18/20 (90%) symptomatic events were associated with progression of presenting symptoms, compared to 2/20 (10%) with a clear recurrent stroke distinct from the original event. We found a low risk of recurrent stroke among classical definition TIA patients (1.1%). Patients with an NIHSS=0 in the ED, had an intermediate event rate (6.6%) between TIA (classical - 1.1%) and NIHSS >0 (14.4%; chi(2) test for trend, P=0.02). All clinical categories of patient (TIA, stroke, NIHSS=0) accumulated silent lesions on MRI. Most events were classified as stroke progression or infarct growth rather than a recurrent stroke. A low risk of recurrence was found in patients with classical TIA and those with no neurological deficits on initial assessment.

Maternal and perinatal outcome in women with a history of stroke

Objective The purpose of this study was to determine recurrence risk and pregnancy outcome in 23 women with a history of stroke. Study design We conducted a descriptive study of 23 women (35 pregnancies) with a history of stroke. Charts were reviewed from 1990 through 2002. The data were analyzed for the antenatal treatment strategies, recurrence risk for stroke, and pregnancy outcome. Results There were 23 study patients with 35 subsequent pregnancies. Associated risk factors of the stroke were thrombophilia (5 women), sickle cell disease (3 women), maternal cardiac malformations (3 women), hypertension (3 women), oral contraceptive use (2 women), cerebral arteriovenous malformations (2 women), head trauma (1 woman), meningitis (1 woman), endocarditis (1 woman), and idiopathic reason (2 women). Four women with 9 subsequent pregnancies had a stroke that was associated with a previous pregnancy or postpartum incident. Two of these 9 pregnancies received anticoagulation (heparin, 1 pregnancy; heparin plus aspirin, 1 pregnancy). Nineteen women with 26 subsequent pregnancies had a stroke before pregnancy. Nine of these 26 pregnancies received anticoagulation (heparin, 5 pregnancies; aspirin, 3 pregnancies; heparin plus aspirin, 1 pregnancy). The remaining pregnancies did not receive prophylactic anticoagulation. Overall, there were 21 term deliveries, 8 preterm deliveries, 5 miscarriages, and 1 fetal death. Three of 34 pregnancies (9%) were small for gestational age infants. There were no recurrent thrombotic episodes during pregnancy or after delivery. Maternal complications included admission to the intensive care unit for uncontrolled hypertension in 1 patient. Conclusion Women with a history of stroke have a low risk of recurrent stroke (0%). This information is useful for the prepregnancy counseling of such individuals. The need for prophylactic anticoagulation in patients with a previous stroke cannot be answered by this study.

Maternal and perinatal outcome in women with a history of stroke

Objective The purpose of this study was to determine recurrence risk and pregnancy outcome in 23 women with a history of stroke. Study design We conducted a descriptive study of 23 women (35 pregnancies) with a history of stroke. Charts were reviewed from 1990 through 2002. The data were analyzed for the antenatal treatment strategies, recurrence risk for stroke, and pregnancy outcome. Results There were 23 study patients with 35 subsequent pregnancies. Associated risk factors of the stroke were thrombophilia (5 women), sickle cell disease (3 women), maternal cardiac malformations (3 women), hypertension (3 women), oral contraceptive use (2 women), cerebral arteriovenous malformations (2 women), head trauma (1 woman), meningitis (1 woman), endocarditis (1 woman), and idiopathic reason (2 women). Four women with 9 subsequent pregnancies had a stroke that was associated with a previous pregnancy or postpartum incident. Two of these 9 pregnancies received anticoagulation (heparin, 1 pregnancy; heparin plus aspirin, 1 pregnancy). Nineteen women with 26 subsequent pregnancies had a stroke before pregnancy. Nine of these 26 pregnancies received anticoagulation (heparin, 5 pregnancies; aspirin, 3 pregnancies; heparin plus aspirin, 1 pregnancy). The remaining pregnancies did not receive prophylactic anticoagulation. Overall, there were 21 term deliveries, 8 preterm deliveries, 5 miscarriages, and 1 fetal death. Three of 34 pregnancies (9%) were small for gestational age infants. There were no recurrent thrombotic episodes during pregnancy or after delivery. Maternal complications included admission to the intensive care unit for uncontrolled hypertension in 1 patient. Conclusion Women with a history of stroke have a low risk of recurrent stroke (0%). This information is useful for the prepregnancy counseling of such individuals. The need for prophylactic anticoagulation in patients with a previous stroke cannot be answered by this study.

Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack

Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) have been identified as potential risk factors for stroke, but information about the risk of recurrent cerebral ischemia is scarce. The aim of this retrospective study was to assess the absolute risk of recurrent cerebrovascular events in 132 patients under 60 years of age with patent foramen ovale, atrial septal aneurysm (diagnosed by transesophageal echocardiography with a contrast study), or both and an otherwise unexplained stroke or transient ischemic attack (TIA). During a mean follow-up of 22.6 ± 16 months, six patients had a recurrent stroke ( n = 2) or a TIA ( n = 4). No systemic embolism was observed. The actuarial risk of having a recurrent stroke was 2.3% (95% confidence interval, 0.6% to 8.2%) at 2 years, whereas the risk of having a stroke or a TIA was 6.7% (95% confidence interval, 3.1% to 14.2%) at 2 years. The average annual rates of recurrence were 1.2% and 3.4%, respectively. In patients with both PFO and ASA, the actuarial risk of a first recurrent stroke was 9.0% (95% confidence interval, 2.4% to 28.5%) at 2 years, with an average annual rate of recurrence of 4.4%. As a group, patients with patent foramen ovale, atrial septal aneurysm, or both and an otherwise unexplained stroke or TIA appear to have a low risk of recurrent stroke whatever the prophylactic antithrombotic therapy used. The association of ASA and PFO may be an indicator of a higher risk of recurrent stroke.