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

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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Long-term clinical outcomes after major bleeding in patients with atrial fibrillation: the Fushimi AF registry

European Heart Journal - Quality of Care and Clinical Outcomes ◽

10.1093/ehjqcco/qcaa082 ◽

2020 ◽

Author(s):

Hisashi Ogawa ◽

Yoshimori An ◽

Kenjiro Ishigami ◽

Syuhei Ikeda ◽

Kosuke Doi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Clinical Outcomes ◽

Major Bleeding ◽

Bleeding Event ◽

Community Based ◽

Increased Risk ◽

All Cause Mortality

Abstract Aims Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P < 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P < 0.01), history of major bleeding (7.7% vs. 4.0%; P < 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P < 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06–3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16–3.41; P < 0.01)]. Conclusion In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. Trial registration https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834. (last accessed 22 October 2020)

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The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients

EP Europace ◽

10.1093/europace/euz273 ◽

2019 ◽

Vol 22 (4) ◽

pp. 547-557 ◽

Cited By ~ 9

Author(s):

Daehoon Kim ◽

Pil-Sung Yang ◽

Eunsun Jang ◽

Hee Tae Yu ◽

Tae-Hoon Kim ◽

...

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Clinical Outcomes ◽

Vitamin K ◽

Major Bleeding ◽

Oral Anticoagulant ◽

Vitamin K Antagonist ◽

Increased Risk ◽

Optimal Drug

Abstract Aims To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Methods and results Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013–16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69–0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72–0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91–1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93–1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03–1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. Conclusions In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.

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Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes

Cardiovascular Diabetology ◽

10.1186/s12933-020-01128-y ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Nam Ju Heo ◽

Sang Youl Rhee ◽

Jill Waalen ◽

Steven Steinhubl

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Clinical Symptoms ◽

Screening Program ◽

Renal Involvement ◽

Newly Diagnosed ◽

Mortality And Morbidity ◽

Increased Risk

Abstract Background Diabetes is an independent risk factor for atrial fibrillation (AF), which is associated with increases in mortality and morbidity, as well as a diminished quality of life. Renal involvement in diabetes is common, and since chronic kidney disease (CKD) shares several of the same putative mechanisms as AF, it may contribute to its increased risk in individuals with diabetes. The objective of this study is to identify the relationship between CKD and the rates of newly-diagnosed AF in individuals with diabetes taking part in a screening program using a self-applied wearable electrocardiogram (ECG) patch. Materials and methods The study included 608 individuals with a diagnosis of diabetes among 1738 total actively monitored participants in the prospective mHealth Screening to Prevent Strokes (mSToPS) trial. Participants, without a prior diagnosis of AF, wore an ECG patch for 2 weeks, twice, over a 4-months period and followed clinically through claims data for 1 year. Definitions of CKD included ICD-9 or ICD-10 chronic renal failure diagnostic codes, and the Health Profile Database algorithm. Individuals requiring dialysis were excluded from trial enrollment. Results Ninety-six (15.8%) of study participants with diabetes also had a diagnosis of CKD. Over 12 months of follow-up, 19 new cases of AF were detected among the 608 participants. AF was newly diagnosed in 7.3% of participants with CKD and 2.3% in those without (P < 0.05) over 12 months of follow-up. In a univariate Cox proportional hazard regression analysis, the risk of incident AF was 3 times higher in individuals with CKD relative to those without CKD: hazard ratios (HR) 3.106 (95% CI 1.2–7.9). After adjusting for the effect of age, sex, and hypertension, the risk of incident AF was still significantly higher in those with CKD: HR 2.886 (95% CI 1.1–7.5). Conclusion Among individuals with diabetes, CKD significantly increases the risk of incident AF. Identification of AF prior to clinical symptoms through active ECG screening could help to improve the clinical outcomes in individuals with CKD and diabetes.

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Particulate Matter and Temperature: Increased Risk of Adverse Clinical Outcomes in Patients With Atrial Fibrillation

Mayo Clinic Proceedings ◽

10.1016/j.mayocp.2020.05.046 ◽

2020 ◽

Vol 95 (11) ◽

pp. 2360-2369 ◽

Cited By ~ 1

Author(s):

José Miguel Rivera-Caravaca ◽

Vanessa Roldán ◽

Vicente Vicente ◽

Gregory Y.H. Lip ◽

Francisco Marín

Keyword(s):

Atrial Fibrillation ◽

Particulate Matter ◽

Clinical Outcomes ◽

Increased Risk

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Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction

Open Heart ◽

10.1136/openhrt-2021-001726 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001726

Author(s):

Anthony P Carnicelli ◽

Ruth Owen ◽

Stuart J Pocock ◽

David B Brieger ◽

Satoshi Yasuda ◽

...

Keyword(s):

Quality Of Life ◽

Myocardial Infarction ◽

Atrial Fibrillation ◽

Clinical Outcomes ◽

Oral Anticoagulants ◽

Adverse Outcomes ◽

Increased Risk ◽

History Of ◽

The Impact

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

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Association Between Alkaline Phosphatase and Clinical Outcomes in Patients With Spontaneous Intracerebral Hemorrhage

Frontiers in Neurology ◽

10.3389/fneur.2021.677696 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sijia Li ◽

Wenjuan Wang ◽

Qian Zhang ◽

Yu Wang ◽

Anxin Wang ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Clinical Outcomes ◽

Functional Outcomes ◽

Adverse Outcomes ◽

Spontaneous Intracerebral Hemorrhage ◽

Mortality And Morbidity ◽

The Third ◽

Increased Risk

Background: Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Alkaline phosphatase (ALP) is related to increased risk of cardiovascular events and is also closely associated with adverse outcomes after ischemic or hemorrhagic stroke. However, there are limited data about the effect of ALP on clinical outcomes after ICH. Therefore, we aimed to investigate the relationship between serum ALP level and prognosis in ICH patients.Methods: From January 2014 to September 2016, 939 patients with spontaneous ICH were enrolled in our study from 13 hospitals in Beijing. Patients were categorized into four groups based on the ALP quartiles (Q1, Q2, Q3, Q4). The main outcomes were 30-day, 90-day, and 1-year poor functional outcomes (modified Rankin Scale score of 3–6). Multivariable logistic regression and interaction analyses were performed to evaluate the relationships between ALP and clinical outcomes after ICH.Results: In the logistic regression analysis, compared with the third quartile of ALP, the adjusted odds ratios of the Q1, Q2, and Q4 for 30-day poor functional outcome were 1.31 (0.80–2.15), 1.16 (0.71–1.89), and 2.16 (1.32–3.55). In terms of 90-day and 1-year poor functional outcomes, the risks were significantly higher in the highest quartile of ALP compared with the third quartile after adjusting the confounding factors [90-day: highest quartile OR = 1.86 (1.12–3.10); 1-year: highest quartile OR = 2.26 (1.34–3.80)]. Moreover, there was no significant interaction between ALP and variables like age or sex.Conclusions: High ALP level (>94.8 U/L) was independently associated with 30-day, 90-day, and 1-year poor functional outcomes in ICH patients. Serum ALP might serve as a predictor for poor functional outcomes after ICH onset.

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Management of Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting

Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery ◽

10.1097/imi.0000000000000570 ◽

2018 ◽

Vol 13 (6) ◽

pp. 383-390 ◽

Cited By ~ 1

Author(s):

Ali J. Khiabani ◽

Taylan Adademir ◽

Richard B. Schuessler ◽

Spencer J. Melby ◽

Marc R. Moon ◽

...

Keyword(s):

Atrial Fibrillation ◽

Coronary Artery ◽

Coronary Artery Bypass ◽

Artery Bypass ◽

Maze Procedure ◽

Success Rates ◽

Surgical Ablation ◽

Mortality And Morbidity ◽

Randomized Controlled Studies ◽

Increased Risk

Untreated atrial fibrillation is associated with an increased risk of all-cause mortality and morbidity. Despite the current guidelines recommending surgical ablation of atrial fibrillation at the time of coronary artery bypass surgery, most patients with concomitant atrial fibrillation and coronary artery disease do not receive surgical ablation for their atrial fibrillation. This review reports the efficacy of different surgical ablation techniques used for the treatment of atrial fibrillation during coronary artery bypass. PubMed was systematically searched for studies reporting outcomes of concomitant surgical ablation in coronary artery bypass patients between January 2002 and March 2018. Data were independently extracted and analyzed by two investigators. Twenty-four studies were included. Twelve studies exclusively reported outcomes of surgical ablation in patients undergoing coronary artery bypass, whereas the remaining 12 reported outcomes of concomitant cardiac surgery with subgroup analysis. Only four studies performed the concomitant Cox-Maze procedure. Freedom from atrial tachyarrhythmia was reported as high as 98% at 1 year and 76% at 5 years with Cox-Maze procedure, whereas lesser lesion sets had more variable outcomes, ranging from 35% to 93%. In most studies, the addition of surgical ablation was not associated with increased morbidity and mortality. Although the Cox-Maze procedure had the greatest short- and long-term success rates, most studies comprising the evidence documenting the safety and efficacy of adding surgical ablation were of low or moderate quality. There was a great deal of heterogeneity among study populations, follow-up times, methods, and definition of failure. To establish a consensus regarding a surgical ablation technique for atrial fibrillation in coronary artery bypass population, larger multicenter randomized controlled studies need to be designed.

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

Thrombosis and Haemostasis ◽

10.1160/th12-12-0942 ◽

2013 ◽

Vol 110 (07) ◽

pp. 153-161 ◽

Cited By ~ 18

Author(s):

Robert Ploen ◽

Markus Zorn ◽

Li Sun ◽

Wei Zhou ◽

Roland Veltkamp

Keyword(s):

Atrial Fibrillation ◽

Dabigatran Etexilate ◽

High Dose ◽

Severe Bleeding ◽

Rodent Models ◽

Stroke Patients ◽

Increased Risk ◽

Ischaemia And Reperfusion ◽

Secondary Haemorrhage ◽

Metalloproteinase 9

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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P4758Label adherence of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation: A nationwide study

European Heart Journal ◽

10.1093/eurheartj/ehz745.1134 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H T Yu ◽

P S Yang ◽

E Jang ◽

T H Kim ◽

J S Uhm ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Clinical Outcomes ◽

Vitamin K ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Systemic Embolism ◽

Increased Risk ◽

All Cause Mortality

Abstract Background Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications. Purpose We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes in real-world clinical practice. Methods We evaluated 53,649 AF patients treated with a NOAC using Korean National Health Insurance Service database during the period from January 2013 to December 2016. NOAC doses were classified as either underdosed or overdosed, consistent with U.S. Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality. Results Overall, 16,757 NOAC-treated patients (31.2%) were underdosed, 4,492 were overdosed (8.4%), and 32,400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (71±8 and 75±7 years of age vs. 70±9 years of age, respectively; p<0.001), more likely female (39% and 53% vs. 38%, respectively; p<0.001), and had higher CHA2DS2-VASc scores (4.6±1.7 and 5.3±1.7 vs. 4.5±1.8, respectively; p<0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 vs. 4.03 events/100 patient-years, p<0.001), major bleeding (4.77 vs. 2.94 events/100 patient-years, p<0.001), and all-cause mortality (5.43 vs. 3.05 events/100 patient-years, p<0.001) compared with label-adherent use. Figure 1 Conclusion In routine clinical practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with increased risk for stroke or systemic embolism, major bleeding, and all-cause mortality in Asian patient with AF.

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Differential effect of mechanical thrombectomy and intravenous thrombolysis in atrial fibrillation associated stroke

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-016720 ◽

2020 ◽

pp. neurintsurg-2020-016720

Author(s):

Feras Akbik ◽

Ali Alawieh ◽

C Michael Cawley ◽

Brian M Howard ◽

Frank C Tong ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Clinical Outcomes ◽

Intracranial Hemorrhage ◽

Functional Outcomes ◽

Mechanical Thrombectomy ◽

Intravenous Thrombolysis ◽

Anterior Circulation ◽

Increased Risk ◽

First Pass

BackgroundAtrial fibrillation (AF) associated ischemic stroke has worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Limited data exist about the effect of AF on procedural and clinical outcomes after mechanical thrombectomy (MT).ObjectiveTo determine whether recanalization efficacy, procedural speed, and clinical outcomes differ in AF associated stroke treated with MT.MethodsWe performed a retrospective cohort study of the Stroke Thrombectomy and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4169 patients who underwent MT for an anterior circulation stroke, 1517 (36.4 %) of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.ResultsAF predicted faster procedural times, fewer passes, and higher rates of first pass success on multivariate analysis (p<0.01). AF had no effect on intracranial hemorrhage (aOR 0.69, 95% CI 0.43 to 1.12) or 90-day functional outcomes (aOR 1.17, 95% CI 0.91 to 1.50) after MT, although patients with AF were less likely to receive IVT (46% vs 54%, p<0.0001).ConclusionsIn patients treated with MT, comorbid AF is associated with faster procedural time, fewer passes, and increased rates of first pass success without increased risk of intracranial hemorrhage or worse functional outcomes. These results are in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF associated stroke treated with supportive care and or IVT. These data suggest that MT negates the AF penalty in ischemic stroke.

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