Recurrent Ischemic Events Research Articles

Baseline P2Y12 reactivity, kidney function, and CYP2C19 genotype determine clopidogrel responsiveness in acute stroke

Clopidogrel is the most-widely used platelet P2Y12-inhibitor for secondary-prevention of ischemic stroke. Platelet P2Y12 reactivity before and after inhibitors can be measured with blood sampling by commercialized system. We aimed to evaluate (1) whether high-on-clopidogrel platelet P2Y12 reactivity (HCPR) is associated with short-term vascular events and (2) the predictors of HCPR in acute stroke. The inclusion criterion was patients with acute stroke who received clopidogrel within 12–48 h after the onset. Platelet reactivity was assayed at baseline and after clopidogrel treatment using the VerifyNow system. The primary endpoint was recurrent ischemic events within 21 days after stroke. Among 190 patients, 32(16.9%) had recurrent ischemic stroke. Multivariate analyses showed that HCPR was significantly associated with the short-term events with an odds-ratio of 2.5 (95% CI 1.1–5.7, p = 0.027). Patients with HCPR had significantly higher frequencies of high baseline platelet P2Y12 reactivity, impaired kidney function, and carrying one or two CYP2C19 loss-of-function alleles. A poor clopidogrel response score combining these factors was developed. Ten percent of patients with score 0, 20.3% of those with score 1, 38.3% of those with score 2, and 66.7% of those with score 3 had HCPR (χ2-test, p < 0.001). Multivariate analyses showed that, compared with the score-0 group, the score-2 and -3 groups had higher risks of HCPR with hazard-ratios of 5.4 (95% CI 1.5–20.3, p = 0.012) and 17.4 (95% CI 3.4–88.9, p = 0.001) for developing recurrent ischemic strokes. The study emphasized the role of HCPR in ischemic stroke. We also developed an HCPR risk score, which could be used in clinical practice or trials, potentially with more precision, to weigh the clinical benefit of a tailored antiplatelet-strategy for patients with stroke.

Association between lipoprotein(a) and long-term outcomes after percutaneous coronary intervention for lesions with in-stent restenosis

ObjectivesThis study aimed to evaluate the association between increased lipoprotein (a) [Lp(a)] and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). BackgroundElevated Lp(a) is demonstrated to be associated with recurrent ischemic events after PCI. However, the impact of Lp(a) in patients with ISR remains undetermined. MethodsBetween January 2017 and December 2018, a total of 2086 patients who underwent PCI for ISR were consecutively enrolled. Patients were categorized as elevated group (> 30 mg/dL, n=834) and non-elevated group (≤ 30 mg/dL, n=1252) according to baseline Lp(a) levels. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. ResultsDuring a median follow-up of 36 months, the primary outcome occurred in 202 of 1252 patients (26.7%) in the elevated Lp(a) group and 237 of 834 patients (21.8%) in the non-elevated Lp(a) group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of all-cause death (4.1% vs. 2.5%, P = 0.002 by Log-rank test; aHR: 1.77; 95% CI: 1.07-2.94; P = 0.03) and repeat revascularization (22.3% vs. 19.5%, P = 0.04 by Log-rank test; aHR: 1.18; 95% CI: 0.94-1.49; P = 0.16). Adding continuous or categorical Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. The results were consistent across subgroups. ConclusionsIn the current cohort of patients who underwent PCI for ISR, elevated Lp(a) at baseline is associated with higher risk of long-term MACE.

Patent foramen ovale closure in non-elderly and elderly patients with cryptogenic stroke: a hospital-based cohort study.

The efficacy of patent foramen ovale (PFO) closure in the elderly population is unclear. We aimed to investigate the efficacy and safety of PFO closure in non-elderly and elderly patients. Patients over 18 years of age with cryptogenic stroke (CS) or transient ischemic attack and PFO were prospectively enrolled and classified into two groups according to treatment: (1) closure of PFO (the PFOC group) and (2) medical treatment alone (the non-PFOC group). The primary outcome was a composite of recurrent cerebral ischemic events and all-cause mortality during the follow-up period. A modified Ranking Scale [mRS] at 180 days was recorded. The safety outcomes were procedure-related adverse events and periprocedural atrial fibrillation. The results between the PFOC and non-PFOC groups in non-elderly (<60 years) and elderly (≥60 years) patients were compared. We enrolled 173 patients, 78 (45%) of whom were elderly. During a mean follow-up of 2.5 years, the incidence of primary outcome was significantly lower in the PFOC group (6.2% vs. 17.1%, hazard ratio[HR] = 0.35, 95% CI 0.13-0.97, p = 0.043) in adjusted Cox regression analysis. Compared with the non-PFOC group, the PFOC group had a numerically lower risk of the primary outcome in both the elderly (HR 0.26, 95% CI 0.07-1.01, p = 0.051) and the non-elderly (HR 0.61, 95% CI 0.11-3.27, p = 0.574) groups. In addition, patients with PFO closure in the elderly group had a lower median mRS at 180 days (p = 0.002). The rate of safety outcome was similar between the non-elderly and elderly groups. PFO closure was associated with a reduced risk of the primary outcome in patients with PFO and CS in our total cohort, which included non-elderly and elderly patients. Compared to those without PFO closure, elderly patients with PFO closure had a better functional outcome at 180 days. PFO closure might be considered in selected elderly patients with PFO.

Stroke recurrence is associated with unfavorable intracranial venous outflow in patients with symptomatic intracranial atherosclerotic large vessel severe stenosis or occlusion.

The purpose of this study was to investigate the predictive value of intracranial venous outflow for recurrent cerebral ischemic events (RCIE) in patients with symptomatic intracranial atherosclerotic large-vessel severe stenosis or occlusion (sICAS-S/O). This retrospective study included sICAS-S/O patients with anterior circulation who underwent dynamic computed tomography angiography (dCTA) and computed tomography perfusion (CTP). Arterial collaterals were evaluated using the pial arterial filling score for dCTA data, tissue-level collaterals (TLC) were assessed using the high-perfusion intensity ratio (HIR, Tmax >10 s/Tmax >6 s), and cortical veins were evaluated using the multi-phase venous score (MVS) for the vein of Labbé (VOL), sphenoparietal sinus (SPS), and superficial cerebral middle vein (SCMV). The relationships between multi-phase venous outflow (mVO), TLC, and 1-year RCIE were analyzed. Ninety-nine patients were included, 37 of whom had unfavorable mVO (mVO-) and 62 of whom had favorable mVO (mVO+). Compared with the mVO+ patients, mVO- patients had a higher admission National Institutes of Health Stroke Scale (NIHSS) score (median, 4 [interquartile range (IQR), 0-9] vs. 1 [IQR, 0-4]; p = 0.048), larger ischemic volume (median, 74.3 [IQR, 10.1-177.9] vs. 20.9 [IQR, 5-86.4] mL; p = 0.042), and worse tissue perfusion (median, 0.04 [IQR, 0-0.17] vs. 0 [IQR, 0-0.03]; p = 0.007). Multivariate regression analysis showed that mVO- was an independent predictor of 1-year RCIE. For patients with sICAS-S/O of the anterior circulation, unfavorable intracranial venous outflow is a potential imaging indicator for predicting higher 1-year RCIE risk.

Low-dose rivaroxaban: can cardiovascular events be reduced?

Despite available effective guideline-based preventive therapies, patients with vascular diseases remain at high-risk of recurrent ischaemic events. Novel therapeutic strategies are therefore needed in order to further reduce the residual risk that is present in these high-risk patients. The Cardiovascular Outcomes for People using Anticoagulation Strategies trial demonstrated that, in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), a combination of rivaroxaban 2.5 mg/bid (vascular dose) and acetylsalicylic acid (ASA) 100 mg once daily, the so-called dual pathway inhibition (DPI), reduced cardiovascular death, stroke, or myocardial infarction by 24% and mortality by 18%, as compared with ASA-alone. The rationale that can explain the improvement of cardiovascular outcome is that platelet aggregation and fibrin formation are involved in arterial thrombosis and rivaroxaban is able to target both ways and has a synergic effect with ASA. The aim of this review is to discuss the potential mechanisms and added benefits of DPI, in patients with PAD and CAD.

Is Dual Antiplatelet Therapy Underutilized Following TIA and Minor Stroke? (S3.006)

<h3>Objective:</h3> Our aim was to identify the variations in single vs dual antiplatelet prescribing practices at the time of discharge within a major Stroke Clinical Network. <h3>Background:</h3> Initiation of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel plays a significant role in the secondary prevention of recurrent acute ischemic events following high risk transient ischemic attack (TIA) and minor acute ischemic stroke (AIS). However, some patients do not receive the same targeted therapy on discharge and are only maintained on single antiplatelet therapy. <h3>Design/Methods:</h3> The GWTG registry was queried for patients &gt;18 years old with a TIA or a minor AIS (NIHSS ≤5), who were admitted to a single hospital network between January 2018 and December 2021. Demographics collected including age, race, gender, and BMI. Patients on concurrent anticoagulation were excluded. We evaluated antiplatelet discharge practices at the tertiary stroke center vs the entire network, among men vs. women, African Americans (AA) vs whites, age 18–70 vs &gt;70 years, and across BMI. <h3>Results:</h3> Among 2953 patients with a TIA or minor AIS, the mean age was 67.3 (SD +/− 13.8 years), with 42% &gt;70 years of age. 47.8% were women; 37% were AA; 60% were white. DAPT was prescribed at the time of discharge to 40% of patients overall. Gender was a significant factor with men (43%) more likely to get prescribed DAPT than females (37%) (p=.002). While BMI did not have a lone effect on number of antiplatelets (AP) prescribed, when it was included as a covariate, there was a significant effect on the number of AP prescribed; with the higher the BMI, the less likely patients were to receive DAPT. <h3>Conclusions:</h3> We identified underutilization of DAPT following TIA and minor stroke across a health system, especially in women. Targeted intervention to increase DAPT use could lead to reduced rate of short-term stroke recurrence. <b>Disclosure:</b> Dr. Solomonow has nothing to disclose. Dr. Marks has nothing to disclose. Karen Yarbrough has nothing to disclose. Dr. Mehndiratta has nothing to disclose. Dr. Chaturvedi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Chaturvedi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Calgary. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Ramar &amp; Paradiso. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Cole, Scott, Kissane. The institution of Dr. Chaturvedi has received research support from NINDS.

Managing Recurrent Ischemic Cerebrovascular Events in Patients with Atrial Fibrillation Compliant with Oral Anticoagulant Therapy (P6-5.001)

<h3>Objective:</h3> To evaluate if oral anticoagulant therapy change (OAC change) or adding antiplatelet therapy to anticoagulation (AC+AP) in patients with nonvalvular atrial fibrillation (AF) and acute ischemic stroke (AIS) or transient ischemic attack (TIA) despite OAC compliance, is associated with lower risk of recurrent cerebrovascular events compared to patients that continued the same anticoagulant regimen. <h3>Background:</h3> Patients with AF still have an appreciable risk of AIS or TIA despite compliance with OAC. Yet little is known about the best management options in this population. <h3>Design/Methods:</h3> We reviewed all consecutive patients with AF on OAC that presented with AIS/TIA to our tertiary academic stroke center between 2011–2021. Baseline characteristics, type of index event, antithrombotic therapy before and after index event, subsequent recurrent AIS/TIA or major bleeding events were extracted. Fisher’s exact or Log-rank tests and logistic regression models were used to compare outcomes between OAC unchange vs OAC change, and AC+AP vs AC only groups. <h3>Results:</h3> 185 patients (mean age 78.3 ± 12 years) were included. 61% were males and 79 (42.7%) had AIS at index event. 17 (9%) had OAC change and 100 (79%) received AP+AC. 39 (21.15%) had recurrent AIS/TIA, and 28 (15.1%) had major bleeding following the index event. No significant difference was observed between OAC unchange versus OAC change groups regarding recurrent AIS/TIA (HR = 0.607, 95% CI: 0.229–1.609, p = 0.316) or major bleeding events (OR = 1.541, 95% CI: 0.391–10.299, p = 0.586). Additionally, no significant difference was observed between AC+AP versus AC groups regarding recurrent AIS/TIA (HR= 0.863, 95% CI: 0.430–1.732, p = 0.679) or major bleeding events (OR= 0.894, 95% CI: 0.377–2.135, p = 0.798). <h3>Conclusions:</h3> In patients with AF and acute ischemic cerebrovascular events despite OAC compliance, changing anticoagulant or adding antiplatelet agent may not decrease risk of future cerebrovascular events. <b>Disclosure:</b> Dr. Harahsheh has nothing to disclose. Mr. Elshaigi has nothing to disclose. Dr. Alhayek has nothing to disclose. Vanesa Vanderhye has nothing to disclose. Dr. O’Carroll has nothing to disclose. Dr. Dumitrascu has nothing to disclose.

Physician Approaches to the Initial Management of an Intraluminal Thrombus in Recently Symptomatic Carotid Artery Stenosis: Results from the Hot Carotid Study (S20.005)

Physician Approaches to the Initial Management of an Intraluminal Thrombus in Recently Symptomatic Carotid Artery Stenosis: Results from the Hot Carotid Study (S20.005)

Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease.

Right ventricular (RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction (HFpEF). Coronary artery disease (CAD) can contribute to the pathophysiological characteristics of HFpEF. This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD. This prospective study included 250 consecutive acute HFpEF patients with CAD. Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value, based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). The primary endpoint was a composite of all-cause death, recurrent ischemic events, and HF hospitalizations. TAPSE/PASP ≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling (area under the curve, 0.731; sensitivity, 61.4%; and specificity, 76.6%). Of the 250 patients, 150 and 100 patients could be grouped into the RV-arterial coupling (TAPSE/PASP >0.43) and uncoupling (TAPSE/PASP ≤0.43) groups, respectively. Revascularization strategies were slightly different between groups; the RV-arterial uncoupling group had a lower rate of complete revascularization (37.0% [37/100] vs . 52.7% [79/150], P <0.001) and a higher rate of no revascularization (18.0% [18/100] vs . 4.7% [7/150], P <0.001) compared to the RV-arterial coupling group. The cohort with TAPSE/PASP ≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP >0.43. Multivariate Cox analysis showed TAPSE/PASP ≤0.43 as an independent associated factor for the primary endpoint, all-cause death, and recurrent HF hospitalization (hazard ratios [HR]: 2.21, 95% confidence interval [CI]: 1.44-3.39, P <0.001; HR: 3.32, 95% CI: 1.30-8.47, P = 0.012; and HR: 1.93, 95% CI: 1.10-3.37, P = 0.021, respectively), but not for recurrent ischemic events (HR: 1.48, 95% CI: 0.75-2.90, P = 0.257). RV-arterial uncoupling, based on TAPSE/PASP, is independently associated with adverse outcomes in acute HFpEF patients with CAD.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world

BackgroundThe risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. MethodsWe used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50–99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. ResultsAmong 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%–5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. ConclusionsIn patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.

Single-center experience of endovascular treatment for patients with progressive posterior circulation cerebral infarction exceeding 24 h.

Evidence of endovascular treatment (ET) for patients with progressive infarction of the posterior circulation exceeding 24 h is lacking. To evaluate the efficacy and safety of ET for progressive posterior circulation cerebral infarction. This retrospective study evaluated the ET for 18 patients with posterior circulation infarction caused by vertebrobasilar artery occlusion from July 2017 to November 2018. The conditions of patients worsened despite receiving intravenous thrombolysis or combination therapy with clopidogrel and aspirin. The time from the onset of cerebral infarction to puncture was >24 h. The preoperative National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and related risk factors of patients at 3 months were analyzed postoperatively. The preoperative NIHSS score was 10.6 (IQR: 6.5), and the time from onset to puncture was 163.5 ± 144.7 h. Postoperative blood flow was modified thrombolysis in cerebral infarction (mTICI) grade 2b or above. During the follow-up period, 1 patient died of basilar artery re-occlusion and pulmonary infection, and 1 died of postoperative hyperperfusion hemorrhage, with a mortality rate of 11.1% (2/18). No recurrent ischemic events were observed in any of the 16 patients during the 3-month follow-up period. The mean mRS score was 1.3 (IQR: 2.3), and 75% patients (12/16) had an mRS score of 0-2. There were no significant differences in age, gender, clinical characteristics, and stroke subtype between patients with mRS scores ≤2 and >2. In patients with progressive posterior circulation cerebral infarction caused by vertebral basilar artery occlusion, ET is effective and safe even if the time from onset to puncture exceeds 24 h.

399 Role of Plaque Inflammation in Symptomatic Carotid Stenosis

INTRODUCTION: Prior studies have shown that plaque inflammation on FDG-PET and the SCAIL score were associated with recurrent ischemic events. However, the findings have thus far not been widely validated. METHODS: This was a single-center prospective cohort study that included patients with (1) recent TIA or ischemic stroke within the past 30 days, (2) ipsilateral carotid artery stenosis of ≥50%, and (3) not considered for early carotid revascularization. The (1) maximum standardized uptake value (SUVmax) of the symptomatic carotid plaque, (2) stenosis severity of the symptomatic carotid artery, and (3) the SCAIL score (a composite score consisting of the degree of plaque inflammation and stenosis severity) were measured for all patients. The outcomes were (1) a 90-day ipsilateral ischemic stroke and (2) a 90-day ipsilateral symptomatic TIA or major adverse cardiovascular event (MACE). RESULTS: Of 131 included patients, 21 (16.0%) patients had a 90-day ischemic stroke, and 41 (31.3%) patients had a 90-day TIA or MACE. Symptomatic plaque SUVmax (AUC = 0.92; 95% CI = 0.82–1.00) was superior to the SCAIL score (AUC = 0.79; 95% CI = 0.65, 0.92) in predicting 90-day ischemic stroke. Symptomatic plaque SUVmax (AUC = 0.84; 95% CI = 0.76, 0.92) was also superior to the SCAIL score (AUC = 0.76; 95% CI = 0.66, 0.85) in predicting 90-day TIA or MACE. CONCLUSIONS: Plaque inflammation may serve as a reliable biomarker for risk stratification and selection of patients for carotid revascularization and/or anti-inflammatory therapy.

5613251 RAPIDLY PROGRESSING MOYAMOYA SYNDROME IN SICKLE CELL DISEASE -- CASE REPORT

Introduction: Moyamoya syndrome (MMS) is an uncommon cerebrovascular complication of Sickle Cell Disease (SCD) characterized by progressive narrowing of large intracranial vessels and development of small-vessel collaterals. This association leads to a significant risk of ischemic stroke and poor neurologic outcomes. Case description: We present a case of a 5-year-old female child, with irregular follow-up at Pediatric Hematology Consultation due to Sickle Cell Disease, who presented to our hospital with a first ischemic stroke. The magnetic resonance angiography (MRA) showed narrowing of the terminal portions of the right internal carotid artery, the proximal segments of the right middle and anterior cerebral arteries and the A1 segment of left anterior cerebral artery, with multiple collaterals, aspects highly suggestive of MMS. She initiated hydroxycarbamide, acetylsalicylic acid and chronic red blood cell exchange (RBCX) aiming HbS<30% and 3 months later she presented with a new transient ischemic stroke. She was submitted to right encephaloduroarteriosynangiosis (EDAS) and was stable, without new ischemic events, until 1 year later when she presented with a new transient ischemic stroke of the left cerebral territory. Since then, she had multiple recurrent ischemic events with total recovery of neurologic deficits. MRA and Computed tomography (CT) showed multiple diffuse areas of cerebral infarction and bilateral severe segmental stenosis of internal carotid, middle and anterior cerebral arteries. Discussion/Conclusion: The literature review suggests that early detection and surgical revascularization in addition to RBCX could significantly reduce stroke recurrence and improve neurocognitive outcome. However, in this case, despite the recommended treatment, it was not possible to prevent the rapid progression of MMS, revealing the complexity of the approach to these patients.

Debate on dual pathway inhibition: Antiplatelet and anticoagulant therapies in patients undergoing percutaneous coronary intervention at high risk for recurrent ischemic events. Focus on anticoagulation-based strategies

Debate on dual pathway inhibition: Antiplatelet and anticoagulant therapies in patients undergoing percutaneous coronary intervention at high risk for recurrent ischemic events. Focus on anticoagulation-based strategies

Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Efficacy, Safety, and Role of Antiplatelet Drugs in the Management of Acute Coronary Syndrome: A Comprehensive Review of Literature.

Acute coronary syndrome (ACS) is a complex condition characterized by myocardial ischemia or infarctionwhich can lead to significant morbidity and death. Antiplatelet drugs play a crucial role in the management of ACS and have been shown to minimize the incidence of significant adverse cardiovascular events and recurrent myocardial infarction (MI). This comprehensive literature review is intended to summarize current information on the effectiveness, safety, and function of frequently used antiplatelet medications in treating ACS. Aspirin, clopidogrel, prasugrel, ticagrelor, abciximab, tirofiban, dipyridamole, cilostazol, and novel antiplatelets are included in the review. Aspirin's effectiveness as a first-line antiplatelet medication in ACS is well established. It has significantly lowered the risk of serious adverse cardiovascular events. Clopidogrel, prasugrel, and ticagrelor are P2Y12 receptor inhibitors found to lower the incidence of recurrent ischemia episodes in ACS patients. Using glycoprotein IIb/IIIa inhibitors such as abciximab, tirofiban, and eptifibatide is effective in managing ACS, especially in high-risk patients. Dipyridamole effectively reduces the risk of recurrent ischemic events in patients with ACS, particularly when used with aspirin. Cilostazol, a phosphodiesterase III inhibitor, has also been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with ACS. Antiplatelet drugs' safety in managing ACS has also been well established. Aspirin is generally well-tolerated with a low risk of adverse effects, although the risk of bleeding events, particularly gastrointestinal bleeding, cannot be eliminated. The P2Y12 receptor inhibitors have been associated with a small increase in the risk of bleeding events, particularly in patients with a high risk of bleeding. The glycoprotein IIb/IIIa inhibitors are associated with a higher risk of bleeding than other antiplatelet drugs, especially in high-risk patients. To summarize, antiplatelet drugs play a crucial role in the management of ACS, and the efficacy and safety of these drugs have been well-established in the literature. The choice of antiplatelet drugs will depend on the patient's risk factors, including age, comorbidities, and bleeding risk. The novel antiplatelets may offer new therapeutic options for managing ACS, and further studies are needed to determine their role in managing this complex condition.

Secondary Cardiovascular Prevention after Acute Coronary Syndrome: Emerging Risk Factors and Novel Therapeutic Targets.

The control of cardiovascular risk factors, the promotion of a healthy lifestyle, and antithrombotic therapy are the cornerstones of secondary prevention after acute coronary syndrome (ACS). However, many patients have recurrent ischemic events despite the optimal control of traditional modifiable risk factors and the use of tailored pharmacological therapy, including new-generation antiplatelet and lipid-lowering agents. This evidence emphasizes the importance of identifying novel risk factors and targets to optimize secondary preventive strategies. Lipoprotein(a) (Lp(a)) has emerged as an independent predictor of adverse events after ACS. New molecules such as anti-PCSK9 monoclonal antibodies, small interfering RNAs, and antisense oligonucleotides can reduce plasma Lp(a) levels and are associated with a long-term outcome benefit after the index event. The inflammatory stimulus and the inflammasome, pivotal elements in the development and progression of atherosclerosis, have been widely investigated in patients with coronary artery disease. More recently, randomized clinical trials including post-ACS patients treated with colchicine and monoclonal antibodies targeting cytokines yielded promising results in the reduction in major cardiovascular events after an ACS. Gut dysbiosis has also raised great interest for its potential pathophysiological role in cardiovascular disease. This evidence, albeit preliminary and needing confirmation by larger population-based studies, suggests the possibility of targeting the gut microbiome in particularly high-risk populations. The risk of recurrent ischemic events after ACS is related to the complex interaction between intrinsic predisposing factors and environmental triggers. The identification of novel risk factors and targets is fundamental to customizing patient clinical management with a precision medicine perspective.

Medical Therapy After CABG: the Known Knowns, the Known Unknowns, and the Unknown Unknowns.

Medical therapies play a central role in secondary prevention after surgical revascularization. While coronary artery bypass grafting is the most definitive treatment for ischemic heart disease, progression of atherosclerotic disease in native coronary arteries and bypass grafts result in recurrent adverse ischemic events. The aim of this review is to summarize the recent evidence regarding current therapies in secondary prevention of adverse cardiovascular outcomes after CABG and review the existing recommendations as they pertain to the CABG subpopulations. There are many pharmacologic interventions recommended for secondary prevention in patients after coronary artery bypass grafting. Most of these recommendations are based on secondary outcomes from trials which include but did not focus on surgical patients as a cohort. Even those designed with CABG in mind lack the technical and demographic scope to provide universal recommendations for all CABG patients. Recommendations for medical therapy after surgical revascularization are chiefly based on large-scale randomized controlled trials and meta-analyses. Much of what is known about medical management after surgical revascularization results from trials comparing surgical to non-surgical approaches and important characteristics of the operative patients are omitted. These omissions create a group of patients who are relatively heterogenous making solid recommendations elusive. While advances in pharmacologic therapies are clearly adding to the armamentarium of options for secondary prevention, knowing what patients benefit most from each therapeutic option remains challenging and a personalized approach is still required.

Abstract Number ‐ 49: Risk of HT with Early DOACs after Acute Ischemic Stroke: A Pooled Analysis

Introduction The risk of hemorrhagic transformation (HT) in the early phase of acute ischemic stroke (AIS) remains unknown, leading to potential unnecessary delays in initiation of anticoagulation for secondary stroke prevention. We sought to assess the rate of HT associated withdirect oral anticoagulant (DOAC) initiation within and beyond 48 hours after AIS, using a pooled analysis of available published data. Methods A pooled analysis of 6 studies (4 prospective observational blinded outcome studies and2 randomized trials) of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted. The primary endpoint was incident radiographic HT on follow‐up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, mortality within the study period, and follow‐up modified Rankin Scale score.The results were reported as odds ratio (OR) andhazard ratio (HR)with 95% confidence interval (CI). Results We evaluated 509 patients; median infarct volume was1.5 (0.1‐7.8) ml, andmedian National Institutes of Health Stroke Scale was2 (0‐3).Incident radiographic HT was seen on follow‐up scan in 34 (6.8%) patients.DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50]P = 0.32).No patients developed symptomatic HT.Conversely, 31 (6.1%) patients developedrecurrent ischemic events, 64% of which occurred within 14 days.Initiating a DOAC within 48 hours of onset was associated with a trend towards lower rates of recurrent ischemic events, but this was not statistically significant (HR 0.42, [0.17 – 1.008]P = 0.052). In contrast to HT,recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84 – 16.24], p&lt; 0.001). Conclusions Initiation of DOAC within 48 hours after stroke was not associated with decreased risk of recurrent ischemic events, or increasedincident risk of HT. Both recurrent ischemic events and incident HT occurred at similar rates.Unlike HT, however, recurrent ischemic events were associated with poor outcomes.

Abstract Number ‐ 231: Role of Anticoagulation in Recurrent Basilar Artery Thrombosis Secondary to Dolichoectasia, a Case Report

Introduction Basilar artery thrombosis accounts for a small part of ischemic strokes but contributes to one‐fifth of the posterior circulation strokes. Recurrent basilar artery thrombosis secondary to dolichoectasia is caused by abnormal flow in the dilated artery and can result in cerebral ischemia. We present a similar case of recurrent thrombosis with a missed dose of anticoagulation and dehydration on two separate occasions. Methods An 81‐year‐old man with a past medical history of ulcerative colitis with colostomy, provoked deep venous thrombosis presented as a transfer from an outside hospital with acute onset of dysarthria, nausea/vomiting, unsteadiness, and left hemiparesis. CT angiogram of head and neck revealed right vertebral thrombosis extending into the basilar artery with dolichoectasia involving distal right vertebral artery and basilar artery. He was started on heparin infusion with improvement in symptoms and a return to baseline. He was later transitioned to apixaban and discharged home. On a follow‐up office visit two months later, his repeat CT angiogram revealed resolution of the thrombus. He was advised to continue the medication due to the risk of recurrent occlusion secondary to vessel anomaly. After four months, the patient returned to the emergency department with acute onset dizziness, imbalance, nausea, and vomiting. CT angiogram of the head and neck was performed which revealed non‐occlusive thrombosis in the basilar artery. On evaluation by neurology, he admits to three missed doses of apixaban. Clinical and laboratory data were concerning for volume depletion. On further questioning about his symptoms, he mentions decreased oral intake on the day of colostomy change. He was advised to continue apixaban and stay hydrated. Results After fifteen months of the first presentation, the patient is symptom‐free but was continued on anticoagulation with apixaban to prevent recurrent events. Conclusions The role of short‐term and long‐term anticoagulation in basilar artery occlusion is less studied. No prospective trials were done so far to suggest that antithrombotic therapy lowers the risk of recurrent ischemic events and/or anticoagulation is superior to antiplatelets. Dolichoectasia by itself can increase the risk of recurrent thrombosis and dehydration likely facilitated the thrombosis in our patient during the event of missed anticoagulation.