Anticoagulation with dabigatran does not increase secondary intracerebral haemorrhage after thrombolysis in experimental cerebral ischaemia

SummaryDabigatran etexilate (DE) has recently been introduced for stroke prevention in atrial fibrillation, but management of acute ischaemic stroke during therapy with DE is a challenge. Thrombolysis is contrain-dicated because of a presumed increased risk of intracerebral haemorrhagic complications. We studied in different ischaemia models whether DE increases secondary haemorrhage after thrombolysis. C57BL/6 mice were anticoagulated with high-dose DE or warfarin. After 2 hour (h) or 3 h transient filament MCAO, rt-PA was injected. At 24 h after MCAO, secondary haemorrhage was quantified using a macroscopic haemorrhage score and haemoglobin spectrophotometry. Post-ischaemic blood-brain-barrier (BBB) damage was assessed using Evans blue. To increase the validity of findings, the duration of anticoagulation was prolonged in mice (5 x DE over 2 days), and the effect of DE after thrombolysis was also examined in thromboembolic MCAO in rats. Pretreatment with warfarin resulted in significantly more secondary haemorrhage (mean haemorrhage score 2.6 ± 0.2) compared to non-anticoagulated animals (1.7 ± 0.3) and DE (9 mg/kg, 1.6 ± 0.3) in 2 h ischaemia. Also after a 3 h period of ischaemia, haemorrhage was more severe in animals anticoagulated with warfarin compared to 9 mg/kg DE and non-anticoagulated control. Prolonged or enteral dabigatran pretreatment led to identical results. Also, thrombolysis after thromboembolic MCAO in rats did not induce more severe bleeding in DE-treated animals. Mice pretreated with warfarin had higher BBB permeability and increased activation of matrix-metalloproteinase 9. In conclusion, DE does not increase the risk of secondary haemorrhage after thrombolysis in various rodent models of ischaemia and reperfusion. The implications of this finding for stroke patients have to be determined in the clinical setting.

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Abstract 14793: Association Between Cardiac Ejection Fraction and the Size of Stroke

Circulation ◽

10.1161/circ.142.suppl_3.14793 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Muhammad M Alvi ◽

Tamra Ranasinghe ◽

Yasser Kabbani ◽

Mohamad Adnan Alkhouli ◽

Abdul Rahman Tarabishy

Keyword(s):

Atrial Fibrillation ◽

Ejection Fraction ◽

Thrombus Formation ◽

Infarct Volume ◽

Inverse Correlation ◽

Stroke Patients ◽

Increased Risk ◽

Median Volume ◽

Cardiac Ejection Fraction ◽

Low Ejection Fraction

Introduction: Heart failure with low ejection fraction (EF) is a known risk factor for stroke. Low EF is associated with increased risk of thrombus formation and is accompanied with 2 to 3 fold increased risk of stroke. This can happen even in the absence of atrial fibrillation. Hypothesis: Our hypothesis was that size of the stroke will be larger in patients with reduction in EF as compared with cardioembolic strokes in preserved EF. The worse the EF, the more stagnation of blood and poor cardiac output leading higher risk of thrombus formation. It’s also likely that the group with reduced EF form a larger thrombus leading to larger stroke as compared to the group with preserved EF. Methods: For our analysis, we retrospectively reviewed charts for 49 acute ischemic stroke patients without atrial fibrillation. We used transthoracic echocardiogram to determine the EF. There are 25 patients with preserved EF, cutoff > 50%. There were 24 patients in reduced EF group. Both groups were matched for age and cardiovascular risk factors. Infarct volume was manually calculated from T1 MRI using BrainLab software. Results: There is an inverse correlation between EF and infarct volume (r=-.283, p=.048) meaning patients with reduced EF had greater infarct volume. Median infarct volume is higher in reduced EF group (median volume = 36 cm 3 ) compared to patients with preserved EF (median volume = 11 cm 3 ) (p=.117). Conclusions: In our patient’s sample, there seems to be an inverse correlation between EF and size of stroke. Patients with reduced EF were associated with larger strokes. Larger studies need to be performed to establish a correlation.

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Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽

10.1161/str.52.suppl_1.p12 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Shadi Yaghi ◽

Eva Mistry ◽

Adam H De Havenon ◽

Christopher Leon Guerrero ◽

Amre Nouh ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Infarct Volume ◽

Intravenous Thrombolysis ◽

The United States ◽

Hemorrhagic Transformation ◽

Stroke Patients ◽

Increased Risk ◽

Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

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Antithrombotic Medication for Cardioembolic Stroke Prevention

Stroke Research and Treatment ◽

10.4061/2011/607852 ◽

2011 ◽

Vol 2011 ◽

pp. 1-23 ◽

Cited By ~ 4

Author(s):

M. Àngels Font ◽

Jerzy Krupinski ◽

Adrià Arboix

Keyword(s):

Atrial Fibrillation ◽

Dabigatran Etexilate ◽

Cardioembolic Stroke ◽

Thrombin Inhibitors ◽

Dose Titration ◽

Modern World ◽

Direct Thrombin Inhibitors ◽

Nonvalvular Atrial Fibrillation ◽

Increased Risk ◽

Clinically Significant

Embolism of cardiac origin accounts for about 20% of ischemic strokes. Nonvalvular atrial fibrillation is the most frequent cause of cardioembolic stroke. Approximately 1% of population is affected by atrial fibrillation, and its prevalence is growing with ageing in the modern world. Strokes due to cardioembolism are in general severe and prone to early recurrence and have a higher long-term risk of recurrence and mortality. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardioembolism and no contraindications for anticoagulation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke. Anticoagulation therapy's associated risk of hemorrhage and monitoring requirements have encouraged the investigation of alternative therapies for individuals with atrial fibrillation. New anticoagulants being tested for prevention of stroke are low-molecular-weight heparins (LMWH), unfractionated heparin, factor Xa inhibitors, or direct thrombin inhibitors like dabigatran etexilate and rivaroxaban. The later exhibit stable pharmacokinetics obviating the need for coagulation monitoring or dose titration, and they lack clinically significant food or drug interaction. Moreover, they offer another potential that includes fixed dosing, oral administration, and rapid onset of action. There are several concerns regarding potential harm, including an increased risk for hepatotoxicity, clinically significant bleeding, and acute coronary events. Therefore, additional trials and postmarketing surveillance will be needed.

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Impact of the Total Number of Carotid Plaques on the Outcome of Ischemic Stroke Patients with Atrial Fibrillation

Journal of Clinical Medicine ◽

10.3390/jcm8111897 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1897 ◽

Cited By ~ 1

Author(s):

Hyungjong Park ◽

Minho Han ◽

Young Dae Kim ◽

Joonsang Yoo ◽

Hye Sun Lee ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Intima Media Thickness ◽

Major Adverse Cardiovascular Events ◽

Stroke Patients ◽

Term Outcome ◽

Long Term Outcome ◽

Increased Risk ◽

Prognostic Utility

Background: Atrial fibrillation (AF) shares several risk factors with atherosclerosis. We investigated the association between total carotid plaque number (TPN) and long-term prognosis in ischemic stroke patients with AF. Methods: A total of 392 ischemic stroke patients with AF who underwent carotid ultrasonography were enrolled. TPN was assessed using B-mode ultrasound. The patients were categorized into two groups according to best cutoff values for TPN (TPN ≤ 4 vs. TPN ≥ 5). The long-term risk of major adverse cardiovascular events (MACE) and mortality according to TPN was investigated using a Cox hazard model. Results: After a mean follow-up of 2.42 years, 113 patients (28.8%) had developed MACE and 88 patients (22.4%) had died. MACE occurred more frequently in the TPN ≥ 5 group than in the TPN ≤ 4 group (adjusted hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.01–2.21; p < 0.05). Moreover, the TPN ≥ 5 group showed an increased risk of all-cause mortality (adjusted HR, 2.69; 95% CI, 1.40–5.17; p < 0.05). TPN along with maximal plaque thickness and intima media thickness showed improved prognostic utility when added to the variables of the CHAD2DS2-VASc score. Conclusion: TPN can predict the long-term outcome of ischemic stroke patients with AF. Adding TPN to the CHAD2DS2-VASc score increases the predictability of outcome after stroke.

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The Risk of Myocardial Infarction in Patients with Atrial Fibrillation Taking a Direct Thrombin Inhibitor: Myths and Reality

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2020-04-17 ◽

2020 ◽

Vol 16 (2) ◽

pp. 301-306

Author(s):

B. A. Tatarsky ◽

N. V. Kazennova ◽

D. A. Napalkov

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Observational Studies ◽

Randomized Clinical Trials ◽

Dabigatran Etexilate ◽

Vascular Complications ◽

Thrombin Inhibitor ◽

Definitive Answer ◽

Increased Risk ◽

Meta Analyses

The purpose of this review is to analyze the results of randomized clinical trials, meta-analyses of cohort and observational studies in real clinical practice on the influence of dabigatran etexilate on the risk of myocardial infarction in patients with atrial fibrillation. A pivotal RE-LY study on dabigatran use in patients with atrial fibrillation did not show statistically significant differences in the frequency of myocardial infarction between any of the doses of dabigatran and warfarin, and the risk of coronary events did not depend on the presence of coronary heart disease or myocardial infarction in the patient's history. Subsequently, a number of meta-analyses have reported an increased risk of myocardial infarction when dabigatran was administered to patients with atrial fibrillation. In general, these studies were characterized by conflicting data, which did not allow to draw any definite conclusions regarding the use of dabigatran in relation to the risk of myocardial infarction. Two FDA cohort observational studies were published in 2014 and 2017, and the former was significantly criticized by experts, and the results of the second study did not provide a definitive answer to the question about the importance of the effect of dabigatran on the development of myocardial infarction in patients with atrial fibrillation. Even more "confusing" the problem arose after the publication of meta-analyses of randomized trials, which showed that the risk of myocardial infarction was increased in patients treated with direct oral anticoagulants compared to patients treated with warfarin. This review provides high quality evidence for the efficacy of dabigatran in preventing myocardial infarction and other vascular complications in patients with atrial fibrillation.

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Newly Detected Atrial Fibrillation after Acute Stroke: A Narrative Review of Causes and Implications

Cardiology ◽

10.1159/000502971 ◽

2019 ◽

Vol 144 (3-4) ◽

pp. 112-121 ◽

Cited By ~ 1

Author(s):

Youcheng Wang ◽

Yongsheng Qian ◽

Daniel Smerin ◽

Shujuan Zhang ◽

Qingyan Zhao ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Stroke ◽

Adverse Outcomes ◽

Stroke Recurrence ◽

Stroke Patients ◽

Increased Risk ◽

Definition Of ◽

Humoral Regulation

Cardiac arrhythmias occur frequently in patients with acute stroke, with atrial fibrillation (AF) being the most common. Newly detected AF may lead to increased risk of ischemic stroke, which in turn generates stroke recurrence and adverse outcomes. Currently, most studies are focusing on the role of AF in ischemic stroke and attributing cryptogenic ischemic stroke to previously undetected AF. However, in these studies, subjects used to have neither symptoms of palpitation nor evidence of AF. A better understanding of this association will contribute to the management and therapy for patients after clinical decisions regarding stroke patients. Currently, the definition of newly detected AF has not come to an agreement, and the pathophysiology remains incompletely understood, possibly involving complex alterations in both the autonomic network and humoral regulation. Therefore, this review aims to introduce the definition and epidemiology of newly detected AF after stroke with updated information and elucidate the potential pathophysiology, such as autonomic imbalance, catecholamine surge, poststroke systematic inflammation, and microvesicles and microRNAs.

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Exposure Response Supports Therapeutic Drug Monitoring for Dabigatran Etexilate in Patients with Atrial Fibrillation

TH Open ◽

10.1055/s-0039-1693486 ◽

2019 ◽

Vol 03 (03) ◽

pp. e210-e215 ◽

Cited By ~ 1

Author(s):

Bryan H. Simpson ◽

David M. Reith ◽

Natalie J. Medlicott ◽

Alesha J. Smith

Keyword(s):

Atrial Fibrillation ◽

Dabigatran Etexilate ◽

Pharmacokinetic Parameters ◽

Population Pharmacokinetic ◽

Response Relationship ◽

Effective Response ◽

Exposure Response ◽

Quartile Range ◽

Increased Risk ◽

Risk Of Hemorrhage

Background Dabigatran etexilate has become widely used for the prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF). Currently, there is limited information in real-world patients relating to dabigatran etexilate exposure and response. Methods This retrospective cohort study used administrative health data for NVAF patients dispensed dabigatran etexilate between July 1, 2011 and December 31, 2015. Outcomes of cerebrovascular accident (CVA), systemic embolism, and hemorrhage were extracted. Simulated pharmacokinetic parameters were obtained using a published population pharmacokinetic model of dabigatran etexilate. Area under the curve calculated for a 24-hour period at steady state (AUCss), the exposure parameter, was derived using these simulations and the dosing data and the exposure–response relationship were investigated. The risk of adverse outcomes at AUCss quartiles was compared using Poisson regression and expressed using incidence rate ratios (95% confidence interval) adjusted for known potential confounders. Results In total, 2,660 NVAF patients had been dispensed dabigatran etexilate. For these patients there was a decreased risk of hemorrhage (0.51, 0.32–0.79) when dabigatran AUCss was in the second quartile range of 1.70 to 1.96 mg h/L and thromboembolism/CVA (0.34, 0.16–0.76) when in the third quartile range of 1.97 to 2.26 mg h/L. An increased risk of hemorrhage (1.68, 1.18–2.38) was observed when AUCss was in the fourth quartile range of 2.27 to 12.76 mg h/L. Conclusion An exposure–response relationship for dabigatran etexilate was described, where the most effective response was observed when AUCss was in the range of 1.70 to 2.26 mg h/L. Hence, it is feasible to develop guidance for optimal dosing to improve outcomes for patients with NVAF.

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Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation

Thrombosis and Haemostasis ◽

10.1160/th14-02-0118 ◽

2014 ◽

Vol 111 (05) ◽

pp. 981-988 ◽

Cited By ~ 74

Author(s):

Torben Larsen ◽

Lars Rasmussen ◽

Gregory Y. H. Lip ◽

Flemming Skjøth

Keyword(s):

Atrial Fibrillation ◽

Gastrointestinal Bleeding ◽

Ischaemic Stroke ◽

Major Bleeding ◽

Stroke Prevention ◽

Dabigatran Etexilate ◽

Indirect Comparison ◽

High Dose ◽

Efficacy And Safety ◽

Comparison Analysis

SummaryLarge Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF) have compared non-vitamin K antagonist oral anticoagulants (NOACs) against warfarin, with the edoxaban trial only recently reported. In the absence of head to head trials directly comparing these NOACs against each other, we compared the efficacy and safety of edoxaban to other agents by an indirect comparison analysis. We performed an indirect comparison analysis of edoxaban (2 dose strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and rivaroxaban (1 dose), for their relative efficacy and safety against each other. For high-dose edoxaban vs apixaban, there were no significant differences in efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban was associated with less major or clinically relevant non-major bleeding (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70–0.90) and gastrointestinal bleeding (HR 0.72; 95% CI 0.53–0.99). For dabigatran 110 mg twice daily, there were no significant differences in the main efficacy or safety endpoints. Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR 0.75; 95% CI 0.56–0.99), stroke (HR 0.73; 95% CI 0.55–0.96) and haemorrhagic stroke (HR 0.48; 95% CI 0.23–0.99). There were no significant differences between high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but rivaroxaban had more major and/or clinically relevant non-major bleeding. When compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR 0.70; 95% CI 0.55–0.89), stroke (HR 0.70; 95% CI 0.55–0.92) and ischaemic stroke (HR 0.65; 95% CI 0.50–0.89), but more major bleeding (HR 1.47; 95% CI 1.20–1.80). For dabigatran 110 mg bid, there were no significant differences in the efficacy endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal) bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower stroke/SE and ischaemic stroke, but higher bleeding rates. In the present analysis, we have provided for the first time, comparisons of efficacy and safety of edoxaban against other NOACs. Notwithstanding the significant limitations of an indirect comparison analysis, some differential effects are evident with the NOACs for stroke prevention, allowing us to allow the prescriber a ‘choice’ to be able to fit the drug to the patient clinical profile (and vice versa).Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

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Statin Therapy in Post-Operative Atrial Fibrillation: Focus on the Anti-Inflammatory Effects

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8030024 ◽

2021 ◽

Vol 8 (3) ◽

pp. 24

Author(s):

Homa Nomani ◽

Amir Hooshang Mohammadpour ◽

Željko Reiner ◽

Tannaz Jamialahmadi ◽

Amirhossein Sahebkar

Keyword(s):

Atrial Fibrillation ◽

Cardiac Surgery ◽

Safety Concern ◽

Artery Bypass ◽

Treatment Strategies ◽

Kidney Injury ◽

High Dose ◽

Increased Risk ◽

Effective Option ◽

Anti Inflammatory

Background: Atrial fibrillation (AF) occurring after cardiac surgery, post-operative AF (POAF), is a serious and common complication of this treatment. POAF may be life-threatening and the available preventive strategies are insufficient or are associated with significantly increased risk of adverse effects, especially in long-term use. Therefore, more appropriate treatment strategies are needed. Methods: In this paper, the efficacy, safety, and other aspects of using statins in the prevention of POAF focusing on their anti-inflammatory effects are reviewed. Results: Recent studies have suggested that inflammation has a significant role in POAF, from the first AF episode to its serious complications including stroke and peripheral embolism. On the other hand, statins, the most widely used medications in cardiovascular patients, have pleiotropic effects, including anti-inflammatory properties. Therefore, they may potentially be effective in POAF prevention. Statins, especially atorvastatin, appear to be an effective option for primary prevention of POAF, especially in patients who had coronary artery bypass grafting (CABG), a cardiac surgery treatment associated with inflammation in the heart muscle. However, several large studies, particularly with rosuvastatin, did not confirm the beneficial effect of statins on POAF. One large clinical trial reported higher risk of acute kidney injury (AKI) following high-dose rosuvastatin in Chinese population. In this study, rosuvastatin reduced the level of C-reactive protein (CRP) but did not reduce the rate of POAF. Conclusion: Further studies are required to find the most effective statin regimen for POAF prevention with the least safety concern and the highest health benefits.

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Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels

European Neurology ◽

10.1159/000513767 ◽

2021 ◽

pp. 1-7

Author(s):

Taoli Lu ◽

Xu Yang ◽

Yanli Cai ◽

Chenchen Xie ◽

Bei Zhang

Keyword(s):

Atrial Fibrillation ◽

Clinical Outcomes ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Mortality And Morbidity ◽

Statin Group ◽

Medical Centers ◽

Increased Risk ◽

Electrocardiogram Monitoring ◽

Metalloproteinase 9

Background: Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. Methods: This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. Results: Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (p < 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006–1.018; p < 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007–1.02; p < 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022–1.053; p < 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022–1.55; p < 0.001). Conclusion: Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.

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