Stroke In Atrial Fibrillation Research Articles

Early vs late anticoagulation in acute ischemic stroke with indications outside atrial fibrillation

BackgroundCurrent literature lacks guidance on the safety of administering anticoagulation in acute ischemic stroke with emergent indications that require anticoagulation other than atrial fibrillation. Therefore, we tend to rely on studies investigating acute ischemic stroke in atrial fibrillation for anticoagulation recommendations. MethodsWe retrospectively reviewed data for patients with acute ischemic stroke who had a non-atrial fibrillation emergent indication for anticoagulation (e.g., intra-arterial thrombus, intracardiac thrombus, acute coronary syndrome, acute limb ischemia, deep vein thrombosis and pulmonary embolism) diagnosed within 3 days of acute ischemic stroke. Patients who received anticoagulation ≤ 3 days of stroke onset (Group A) were compared to those who either received it afterwards or did not receive it at all (Group B). ResultsOut of the 558 patients, only 88 patients met our inclusion criteria. Of the total cohort, 55.7 % patients were males, and basic demographics were similar in both groups except for milder strokes in Group A (national institute of health stroke scale 6 vs. 12.5, p = 0.03). Only 2 patients in Group A and 1 patient in Group B developed intracranial hemorrhage, which was not statistically significant. Group A patients had a lower incidence of both new diagnosis (2 % vs. 34.2 % %, p < 0.001) and propagation of an established venous thromboembolism. They also had a lower rate of any thromboembolic complication (2 % vs. 42 %, p < 0.001). ConclusionEarly anticoagulation (i.e., ≤ 3 days) in non-atrial fibrillation ischemic stroke patients with an emergent indication may be safe and carry a lower risk of thromboembolic complications than later anticoagulation.

Early Rhythm Control and Incident Dementia in Patients With Atrial Fibrillation and Prior Stroke.

Although early rhythm control (ERC) in patients with atrial fibrillation (AF) reduces the risk of stroke, there is no evidence thus far on whether ERC reduces the risk of developing dementia in patients with AF and prior stroke. This study sought to evaluate whether ERC reduces the risk of developing dementia in patients with new-onset AF and prior stroke. Using the Korean nationwide claims database, we identified patients with new-onset AF and prior stroke between 2010 and 2016. Patients who received rhythm control therapy within 1 year after AF onset were defined as the ERC group, otherwise patients were categorized as the usual care group. A propensity score weighting method was used to balance the 2 groups. Incident dementia defined by relevant diagnostic codes was evaluated. A total of 41,370 patients were included (mean age 70 ± 11 years; mean CHA2DS2-VASc score 5.3±1.6): 10,213 in the ERC group and 31,157 in the usual care group. Compared with usual care, ERC was associated with lower risks of all dementia, Alzheimer's dementia, and vascular dementia (weighted HRs [95%CIs], 0.825 [0.776-0.876], 0.831 [0.774-0.893], and 0.800 [0.702-0.913], respectively, all P< 0.001). The benefit of ERC was slightly accentuated in the younger age group (<65 years). The beneficial effect of ERC in reducing the risk of dementia was consistent regardless of the characteristics of prior stroke. ERC might be beneficial in the prevention of dementia in patients with AF and prior stroke. To prevent the progression of cognitive dysfunction, ERC should be considered in this population.

Ischaemic stroke in women with atrial fibrillation: temporal trends and clinical implications.

Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P < .001), and the incidence decreased both in men and women. In 2007-08, female sex was independently associated with a 20%-30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF.

Evaluación dinámica de las escalas CHA2DS2-VASc y HAS-BLED para predecir ictus isquémico y hemorragia mayor en pacientes con fibrilación auricular

Introduction and objectivesStroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline to predict outcomes years later. We investigated whether dynamic changes in CHA2DS2-VASc and HAS-BLED scores over time modify risk prediction. MethodsWe included patients with AF who were stable while taking vitamin K antagonists. During a 6-year follow-up, all ischemic strokes/transient ischemic attacks (TIAs) and major bleeding events were recorded. CHA2DS2-VASc and HAS-BLED were recalculated every 2-years and tested for clinical outcomes at 2-year periods. ResultsWe included 1361 patients (mean CHA2DS2-VASc and HAS-BLED 4.0±1.7 and 2.9±1.2). During the follow-up, 156 (11.5%) patients had an ischemic stroke/TIA and 269 (19.8%) had a major bleeding event. Compared with the baseline CHA2DS2-VASc, the CHA2DS2-VASc recalculated at 2 years had higher predictive ability for ischemic stroke/TIA during the period from 2 to 4 years. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) showed improvements in sensitivity and better reclassification. The CHA2DS2-VASc recalculated at 4 years had better predictive performance than the baseline CHA2DS2-VASc during the period from 4 to 6 years, with an improvement in IDI and an enhancement of the reclassification. The recalculated HAS-BLED at 2-years had higher predictive ability than the baseline score for major bleeding during the period from 2 to 4 years, with significant improvements in sensitivity and reclassification. A slight enhancement in sensitivity was observed with the HAS-BLED score recalculated at 4 years compared with the baseline score. ConclusionsIn AF patients, stroke and bleeding risks are dynamic and change over time. The CHA2DS2-VASc and HAS-BLED scores should be regularly reassessed, particularly for accurate stroke risk prediction.

Relationship between wait times and post–atrial fibrillation ablation outcomes: A population-based study

BackgroundRhythm control is a cornerstone of atrial fibrillation (AF) management. Shorter time between diagnosis of AF and receipt of catheter ablation is associated with greater rates of therapy success. Previous work considered diagnosis-to-ablation time as a binary or categorical variable and did not consider the unique risk profile of patients after a referral for ablation was made. ObjectiveThe purpose of this study was to comprehensively assess the impact of diagnosis-to-ablation and referral-to-ablation time on postprocedural outcomes at a population level. MethodsThis observational cohort study included patients who received catheter ablation to treat AF in Ontario, Canada. Patient demographics, medical comorbidities, AF diagnosis date, ablation referral date, and ablation date were collected. The primary outcomes of interest included a composite of death and hospitalization/emergency department visit for AF, heart failure, or ischemic stroke. Multivariable Cox models assessed the impact of diagnosis-to-ablation and referral-to-ablation times on the primary outcome. ResultsOur cohort included 7472 patients who received ablation for de novo AF between April 1, 2016, and March 31, 2022. Median [interquartile range] diagnosis-to-ablation time was 718 [399–1274] days and median referral-to-ablation time was 221 [117–363] days. Overall, 911 patients (12.2%) had the composite endpoint within 1 year of ablation. Increasing diagnosis-to-ablation time was associated with a greater incidence for the primary outcome (hazard ratio [HR]1.02; 95% confidence interval [CI] 1.01–1.02 per month). Increasing referral-to-ablation time did not impact the primary outcome (HR 1.00; 95% CI 0.98–1.01 per month). ConclusionDelays between AF diagnosis and ablation referral may contribute to adverse postprocedural outcomes and provide an opportunity for health system quality improvements.

Management of DOAC-related bleeding in cancer patients: a single center-case series.

Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient's specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients.

Using machine learning to identify proteomic and metabolomic signatures of stroke in atrial fibrillation

Atrial fibrillation (AF) is a common cardiac arrhythmia, with stroke being its most detrimental comorbidity. The exact mechanism of AF related stroke (AFS) still needs to be explored. In this study, we integrated proteomics and metabolomics platform to explore disordered plasma proteins and metabolites between AF patients and AFS patients. There were 22 up-regulated and 31 down-regulated differentially expressed proteins (DEPs) in AFS plasma samples. Moreover, 63 up-regulated and 51 down-regulated differentially expressed metabolites (DEMs) were discovered in AFS plasma samples. We integrated proteomics and metabolomics based on the topological interactions of DEPs and DEMs, which yielded revealed several related pathways such as arachidonic acid metabolism, serotonergic synapse, purine metabolism, tyrosine metabolism and steroid hormone biosynthesis. We then performed a machine learning model to identify potential biomarkers of stroke in AF. Finally, we selected 6 proteins and 6 metabolites as candidate biomarkers for predicting stroke in AF by random forest, the area under the curve being 0.976. In conclusion, this study provides new perspectives for understanding the progressive mechanisms of AF related stroke and discovering innovative biomarkers for determining the prognosis of stroke in AF.

Atrial Fibrillation Burden: Impact on Stroke Risk and Beyond.

Atrial fibrillation (AF) is an important independent risk factor for stroke. Current guidelines handle AF as a binary entity with risk driven by the presence of clinical risk factors, which guides the decision to treat with an oral anticoagulant. Recent studies in the literature suggest a dose-response relationship between AF burden and stroke risk, in both clinical AF and subclinical atrial fibrillation (SCAF), which differs from current guidance to disregard burden and utilize clinical risk scores alone. Within clinical classification and at the same risk levels in various scores, the risk of stroke increases with AF burden. This opens the possibility of incorporating burden into risk profiles, which has already shown promise. Long-term rhythm monitoring is needed to elucidate SCAF in patients with stroke. Recent data from randomized trials are controversial regarding whether there is an independent risk from AF episodes with a duration of less than 24 h, including the duration of SCAF greater than six minutes but less than 24 h.

Atrial Fibrillation Complicating Acute Myocardial Infarction: Prevalence, Impact, and Management Considerations.

Atrial fibrillation (AF) and myocardial infarction (MI) often coexist, and this overlapping nature leads to heightened morbidity and increases the need for comprehensive risk management strategies. The precise trajectory and implications of atrial fibrillation complicating myocardial infarction remain subjects of debate, with divergent reports presenting varying accounts. This review seeks to provide an in-depth exploration of the existing literature to cover the predictors, implication, and available management of new onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI). Clinical risk factors, laboratory markers, echocardiographic findings, and angiographic data can be used to assess patients at risk of developing NOAF post-AMI. The diagnosis of NOAF post MI has been associated with overall worse short- and long-term prognosis with increased risk for mortality, cardiogenic shock, stroke, and bleeding, along with reduced rates of coronary angiography and percutaneous coronary intervention, and higher risk of future recurrence of AF and ischemic stroke. Despite the paucity of preventative treatment, the optimal management of acute coronary syndrome and the use of guideline directed therapy do decrease the risk of development of atrial fibrillation post myocardial infarction.

Dynamic assessment of CHA2DS2-VASc and HAS-BLED scores for predicting ischemic stroke and major bleeding in atrial fibrillation patients

Introduction and objectivesStroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline to predict outcomes years later. We investigated whether dynamic changes in CHA2DS2-VASc and HAS-BLED scores over time modify risk prediction. MethodsWe included patients with AF who were stable while taking vitamin K antagonists. During a 6-year follow-up, all ischemic strokes/transient ischemic attacks (TIAs) and major bleeding events were recorded. CHA2DS2-VASc and HAS-BLED were recalculated every 2-years and tested for clinical outcomes at 2-year periods. ResultsWe included 1361 patients (mean CHA2DS2-VASc and HAS-BLED 4.0±1.7 and 2.9±1.2). During the follow-up, 156 (11.5%) patients had an ischemic stroke/TIA and 269 (19.8%) had a major bleeding event. Compared with the baseline CHA2DS2-VASc, the CHA2DS2-VASc recalculated at 2 years had higher predictive ability for ischemic stroke/TIA during the period from 2 to 4 years. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) showed improvements in sensitivity and better reclassification. The CHA2DS2-VASc recalculated at 4 years had better predictive performance than the baseline CHA2DS2-VASc during the period from 4 to 6 years, with an improvement in IDI and an enhancement of the reclassification. The recalculated HAS-BLED at 2-years had higher predictive ability than the baseline score for major bleeding during the period from 2 to 4 years, with significant improvements in sensitivity and reclassification. A slight enhancement in sensitivity was observed with the HAS-BLED score recalculated at 4 years compared with the baseline score. ConclusionsIn AF patients, stroke and bleeding risks are dynamic and change over time. The CHA2DS2-VASc and HAS-BLED scores should be regularly reassessed, particularly for accurate stroke risk prediction.

Factor Xa inhibitors versus warfarin in severely obese patients with venous thromboembolism or atrial fibrillation

Objectives: Clinical data for the safety and efficacy of Factor Xa (FXa) inhibitors in severely obese patients is limited. Additional information is needed to assess the risks and benefits of using FXa inhibitors in this patient population. Materials and Methods: A single-center and retrospective chart review was conducted in severely obese patients (body mass index [BMI] &gt;40 kg/m2 or weight &gt;120 kg), who received rivaroxaban, apixaban or warfarin for venous thromboembolism (VTE) treatment or prevention of stroke and systemic embolism in non-valvular atrial fibrillation (AF). The primary endpoint was treatment failure, defined as recurrent VTE in VTE treatment or stroke, transient ischemic attack or systemic embolism in AF within one year of anticoagulation initiation. Secondary endpoints included a composite of major bleeding rates and clinically relevant non-major bleeding (CRNMB) rates. Results: Seventy-three patients were included in the final analysis consisting of 43 patients in the FXa inhibitor arm (apixaban [n = 33] and rivaroxaban [n = 10]) and 30 patients in the warfarin arm. The rate of treatment failure was similar between the FXa inhibitor and warfarin groups (4.7% vs. 6.7%; P = 0.814). Although not statistically significant, major bleeding and CRNMB occurred less frequently in patients receiving FXa inhibitors compared to warfarin (9.3% vs. 23.3%; P = 0.182). Subgroup analysis in patients with BMI &gt;50 kg/m2 or weight &gt;150 kg demonstrated similar efficacy and safety outcomes. The use of non-recommended dosing was more common in the apixaban group compared to the rivaroxaban group. Conclusion: FXa inhibitors (apixaban and rivaroxaban) appear to have similar efficacy and safety compared to warfarin in severely obese patients. Larger prospective studies are needed to confirm these results.

Epidemiology, prognosis, and challenges in the management of hyperthyroidism-related atrial fibrillation.

Atrial fibrillation (AF) is a common condition with a global estimated prevalence of 60 million cases, and the most common cardiac complication of hyperthyroidism, occurring in 5-15% of overtly hyperthyroid patients. Additionally, subclinical hyperthyroidism and high-normal free T4 have been associated with an increased risk in the development of AF. Hyperthyroidism-related AF is a reversible cause of AF, and the majority of patients spontaneously revert to sinus rhythm in 4-6 months during or after restoration of euthyroidism. Therefore, restoring thyroid function is an indispensable element in hyperthyroidism-related AF management. Rate control with beta-blockers consists another first-line therapy, reserving rhythm control in cases of persistent hyperthyroidism-related AF. It is still controversial whether hyperthyroidism is an independent risk factor of stroke in nonvalvular AF. As a result, initiating anticoagulation should be guided by the clinical thromboembolic risk score CHA2DS2-VASc score in the same way it is applied in patients with non-hyperthyroidism-related AF. Treatment with the novel direct oral anticoagulants appears to be as beneficial and may be safer than warfarin in patients with hyperthyroidism-related AF. In this review, we address the epidemiology, prognosis, and diagnosis of hyperthyroidism-related AF, and we discuss the management strategies and controversies in patients with hyperthyroidism-related AF.

LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation.

The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signaling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and hematologic disorders including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk-/- mice are susceptible to atrial fibrillation (AF) and that rs3184504 is associated with AF and AF-related stroke in humans. During inflammation, reactive lipid dicarbonyls are a major component of oxidative injury, and we further hypothesized that these mediators are critical drivers of the AF substrate in Lnk-/- mice. Lnk-/- or wild-type (WT) mice were treated with vehicle or 2-hydroxybenzylamine (2-HOBA), a dicarbonyl scavenger, for 3 months. Compared to WT, Lnk-/- mice displayed increased AF duration that was prevented by 2-HOBA. In the Lnk-/- atria, action potentials were prolonged with reduced transient outward K+ current, increased late Na+ current, and reduced peak Na+ current, proarrhythmic effects that were inhibited by 2-HOBA. Mitochondrial dysfunction, especially for complex I, was evident in Lnk-/- atria, while scavenging lipid dicarbonyls prevented this abnormality. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were elevated in Lnk-/- plasma and atrial tissue, respectively, both of which caused electrical and bioenergetic remodeling in vitro. Inhibition of soluble TNF-α prevented electrical remodeling and AF susceptibility, while IL-1β inhibition improved mitochondrial respiration but had no effect on AF susceptibility. In a large database of genotyped patients, rs3184504 was associated with AF, as well as AF-related stroke. These findings identify a novel role for LNK in the pathophysiology of AF in both experimental mice and in humans. Moreover, reactive lipid dicarbonyls are critical to the inflammatory AF substrate in Lnk-/- mice and mediate the proarrhythmic effects of pro-inflammatory cytokines, primarily through electrical remodeling.

Practicality and Safety of Electrical Pulmonary Vein Isolation and Left Atrial Appendage Ligation in Lung Transplant Recipients With Pretransplant Atrial Fibrillation.

Lung transplant surgery creates surgical pulmonary vein isolation (PVI) as a routine part of the procedure. However, many patients with pretransplant atrial fibrillation continue to have atrial fibrillation at 1 y. We hypothesized that the addition of electrical PVI and left atrial appendage isolation/ligation (LAL) to the lung transplant procedure restores sinus rhythm at 1 y in patients with pretransplant atrial fibrillation. We retrospectively reviewed all adult lung transplant recipients at the University of California Los Angeles from April 2006 to August 2021. All patients with pretransplant atrial fibrillation underwent concomitant PVI/LAL and were compared with lung transplant recipients without preoperative atrial fibrillation. In-hospital outcomes; 1-y survival; and the incidence of stroke, cardiac readmissions, repeat ablations, and sinus rhythm (composite endpoint) were examined at 1 y for the PVI/LAL cohort. Sixty-one lung transplant recipients with pretransplant atrial fibrillation underwent concomitant PVI/LAL. No patient in the PVI/LAL cohort required cardiac-related readmission or catheter ablation for atrial fibrillation within 1 y of transplantation. Freedom from the composite endpoint of death, stroke, cardiac readmission, and repeat ablation for atrial fibrillation at 1 y was 85% (95% confidence interval, 73%-92%) for lung transplant recipients treated with PVI/LAL. The addition of PVI/LAI to the lung transplant operation in patients with pretransplant atrial fibrillation was safe and effective in maintaining sinus rhythm and baseline risk of stroke at 1 y.

High brain natriuretic peptide level is associated with severe stroke in patients taking oral anticoagulants: A sub-analysis of the PASTA registry study

BackgroundBrain natriuretic peptides (BNP) are an important diagnostic and prognostic marker in patients with heart failure. However, the relationship between BNP levels and stroke severity in patients with atrial fibrillation (AF) remains unelucidated. In this study, we aimed to investigate the association between stroke severity at admission and BNP levels. MethodsIn this prospective observational study, we used data from 513 patients with AF and acute ischemic stroke treated with oral anticoagulants (OAC) registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study. The patients were divided into two groups: high-BNP (≥200 pg/mL) and low-BNP level (<200 pg/mL) groups. We compared the clinical characteristics between the two groups and determined the effect of BNP levels on stroke severity on admission. ResultsAmong the 513 enrolled patients, 248 (females, n = 30; median age, 82 years) and 265 (females, n = 76; median age, 71 years) were assigned to the high- and low-BNP level groups, respectively. The high-BNP level group had a higher proportion of patients with severe stroke (National Institutes of Health Stroke Scale score, ≥10) on admission (49.2% vs. 32.8%, p = 0.002) and major vessel occlusion (57.5% vs. 39.2%, p < 0.0001) than that had by the low-BNP level group. Multivariate analysis showed that high BNP level was independently associated with severe stroke on admission (odds ratio 1.07, 95% confidence interval 1.00–1.15; p = 0.0478). ConclusionsHigh BNP level compared with low BNP level was associated with severe stroke and major vessel occlusion, even before OAC treatment.

The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study.

The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction>0.2500 for all). Similar findings were yielded when assessing theABC-stroke score as a continuous variable. In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study. URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

Abstract 66: Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation: Primary Results of the START Trial

Introduction: Clinical practice guidelines recommend initiation of anticoagulation within 2 weeks after stroke due to atrial fibrillation (AF). It is unknown whether there is an optimal day within that 14-day period that balances the risks of recurrent embolic vs serious hemorrhagic events. Methodology: The Lone Start Stroke START trial is a pragmatic, prospective, multi-center, response-adaptive randomized Phase 2 study of 200 patients prescribed a direct oral anticoagulant (DOAC) for secondary prevention of stroke due to AF. Patients were randomized into one of 4 Arms: Day 3-4 from stroke onset, Day 6, Day 10, or Day 14. The primary outcome was an ischemic (stroke or systemic embolus) or hemorrhagic (ICH or major systemic hemorrhage) event observed within 30 days from the index stroke time of onset. Posterior probabilities that each arm was the best were calculated at predefined intervals and randomization allocations were adjusted to favor the Arms with higher probabilities. Results: The median age was 75 (IQR 65-81), median NIHSS at presentation was 7 (IQR 4-14), median lesion diameter was 3.1 cm (IQR 2.0-4.4) at the time of randomization. The sample was 50% female, 17.5% non-white, and 16.5% Hispanic. Apixaban was the prescribed DOAC in 89% of the patients. No ischemic events were observed for Arm 1, and no hemorrhage events were observed for Arm 4. Arm 1 (3-4 days) had a posterior 41.1% probability of being the best among the four, with probabilities of 26.4%, 17.1%, and 15.4 % respectively, for the other arms. Response adapted randomization was feasible and favored the earlier two arms. Expected event rates for each arm are presented in the Table. The timing and severity of the outcome events will be presented at the conference. Conclusion: Although the START trial did not identify a clearly superior day to initiate DOAC for secondary stroke prevention in AF, the evidence suggests that initiating DOAC early is better than at later times within the first 2 weeks after stroke onset.

Association of Prediabetes and Recurrent Stroke in Atrial Fibrillation Patients: A Population-Based Analysis of Hospitalizations and Outcomes.

Prediabetes is a risk factor for ischemic stroke in atrial fibrillation (AF) patients, yet, its impact on recurrent stroke in AF patients remains understudied. Using the 2018 National Inpatient Sample, we investigated the link between Prediabetes and recurrent stroke in AF patients with prior stroke or transient ischemic attack (TIA). Among 18,905 non-diabetic AF patients, 480 (2.5%) had prediabetes. The prediabetic group, with a median age of 78, exhibited a two-fold higher risk of recurrent stroke compared to the non-prediabetic cohort (median age 82), as evidenced by both unadjusted (OR 2.14, 95% CI 1.72-2.66) and adjusted (adjusted for socio-demographics/comorbidities, OR 2.09, 95% CI 1.65-2.64, p < 0.001). The prediabetes cohort, comprising more male and Black patients, demonstrated associations with higher Medicaid enrollment, admissions from certain regions, and higher rates of hyperlipidemia, smoking, peripheral vascular disease, obesity, and chronic obstructive pulmonary disease (all p < 0.05). Despite higher rates of home health care and increased hospital costs in the prediabetes group, the adjusted odds of all-cause mortality were not statistically significant (OR 0.55, 95% CI 0.19-1.56, p = 0.260). The findings of this study suggest that clinicians should be vigilant in managing prediabetes in AF patients, and strategies to prevent recurrent stroke in this high-risk population should be considered.

Effect of atherosclerosis on the relationship between atrial fibrillation and ischemic stroke incidence among patients on hemodialysis

In patients undergoing hemodialysis, the impact of atrial fibrillation (AF) through cardiac thromboembolism on the development of ischemic stroke may be influenced by the severity of atherosclerosis present. However, there are no large-scale reports confirming whether the severity of atherosclerosis influences the relationship between AF and stroke development in patients requiring hemodialysis. We aimed to investigate the effects of atherosclerotic disease on the relationship between AF and new-onset ischemic stroke. This nationwide longitudinal study based on dialysis facilities across Japan used data collected from the Japanese Renal Data Registry at the end of 2019 and 2020. The exposure was AF at the end of 2019, identified using a resting 12-lead electrocardiography. The primary outcome was the incidence of cerebral infarction (CI) after 1 year. To examine whether the number of atherosclerotic diseases modified the association between AF and the outcome, we estimated the odds ratios (ORs) using a logistic regression model and then assessed the presence of global interaction using Wald test. Following the study criteria, data from 151,350 patients (mean age, 69 years; men, 65.2%; diabetic patients, 48.7%) were included in the final analysis. A total of 9841 patients had AF (prevalence, 6.5%). Between 2019 and 2020, 4967 patients (3.2%) developed ischemic stroke. The adjusted OR of AF for new-onset CI was 1.5, which showed a decreasing trend with an increasing number of atherosclerotic diseases; the interaction was not significant (P = 0.34). While age, diabetes mellitus, smoking, systolic blood pressure, and serum C-reactive protein concentration were positively associated with CI, intradialytic weight gain, body mass index, and serum albumin level were negatively associated. While we demonstrated the association between AF and new-onset CI among Japanese patients on hemodialysis, we failed to demonstrate the evidence that the association was attenuated with an increasing numbers of atherosclerotic complications.

Cardiovascular Events and Mortality in Patients on Hemodialysis: The Prognostic Value of the CHA2DS2-VASc Score.

Background and Objectives: Cardiovascular events are the major cause of morbidity and mortality in patients on hemodialysis (HD). Identifying risk factors can help in the effort to reduce cardiovascular risk and improve life expectancy. The objective of this study was to evaluate the ability of the CHA2DS2-VASc score-the risk index of stroke in atrial fibrillation (AF)-to predict strokes, major cardiovascular events, and mortality in patients with end-stage kidney disease. Materials and Methods: The CHA2DS2-VASc and HAS-BLED scores (the bleeding risk from the use of anticoagulation in AF) were calculated in 237 HD patients, 99 women with a median age of 76 (15) years, at the time they commenced HD. The scores' ability to predict long term cardiovascular morbidity and mortality was estimated, both in those with and without AF. Among the exclusion criteria were the change of dialysis method or loss of follow-up, HD due to acute renal failure, and incompliance with medical instructions, thus the sample is not representative of a broader population. Results: The CHA2DS2-VASc score was higher in AF (n = 69) compared to non-AF (n = 168) patients, 5 (2.5) vs. 4 (2), p < 0.0001, respectively. An increased CHA2DS2-VASc score was correlated with cardiovascular events, namely, heart failure (p = 0.007, p = 0.024), stroke (p < 0.0001, p < 0.0001), and risk of all-cause mortality (p < 0.0001, p < 0.0001) in AF and non-AF groups, respectively. The C statistics indicated that the referred score showed modest discrimination in AF and non-AF patients on HD for heart failure, stroke, and all-cause mortality, however for cardiovascular mortality this was found only in the AF group. Conclusions: An increased CHA2DS2-VASc score at the time of HD initiation can predict strokes, heart failure, and all-cause mortality in HD patients independent of the presence of AF. The risk of cardiovascular mortality could only be predicted in patients with AF.