Early Antithrombotic Treatment Research Articles

Analysis of Safety and Efficacy of the Early Initiation of Antithrombotic Secondary Prevention in Patients Treated with Intravenous Thrombolysis for Acute Ischemic Stroke.

Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28-0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome.

Detection of microemboli in patients with acute ischaemic stroke and atrial fibrillation suggests poor functional outcome.

We investigated the burden of microembolic signals (MES) in patients with acute ischaemic stroke (AIS) and atrial fibrillation (AF), assessing their impact on functional outcomes. This multicentre international prospective cohort study involved patients with AIS and either a known or newly diagnosed anticoagulant-naïve AF. All centres utilised the same transcranial Doppler machine for 1-h monitoring with bilateral 2 MHz probes within 24 h of symptom onset. Recordings underwent MES analysis by a blinded central reader. The primary objectives were to ascertain the MES proportion and its association with functional outcomes assessed by the modified Rankin scale (mRS) score at 90 days. Between September 2019 and May 2021, we enrolled 61 patients, with a median age of 78 years (interquartile range 73-83) and a median stroke severity score of 11 (interquartile range 4-18). MES were observed in 14 patients (23%), predominantly unilateral (12/14, 86%), with a median rate of 6 counts/hour (interquartile range 4-18). MES occurrence was higher post-thrombectomy and among those with elevated brain natriuretic peptide levels (p < 0.05). A worse mRS score of 3-6 was more frequent in patients with MES, occurring in 11/14 (79%), compared to those without MES, 20/47 (43%), with an adjusted odds ratio of 5.04 (95% CI, 1.15-39.4), p = 0.04. Nearly a quarter of patients with AIS and AF exhibited silent microembolization after the index event. Detecting MES within 24 h post-stroke (using transcranial Doppler) could signify a marker of poor functional outcomes. Subsequent trials will assess if very early antithrombotic treatment might enhance outcomes in this highly selective group of cardioembolic stroke patients. (Clinicaltrials.gov ID: NCT06018090).

Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction

The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P=.04). In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation.

Central retinal artery occlusion secondary to presumed traumatic carotid artery dissection in a healthy child

PurposeTo describe a rare case of a 13 years-old healthy child that presented CRAO secondary to carotid artery dissection, which occurred after a neck rotation movement.MethodsCase report with prospective literature review.PatientsOne patient described in the case report.ResultsNot applicable.Discussion/conclusionInternal carotid artery dissection is a rare condition, specially in children, that can lead to serious cerebral-ocular ischemic events. It may occur due to direct vessel trauma or spontaneously. Prompt imaging screening is of paramount importance because early antithrombotic treatment or surgical intervention may significantly reduce the incidence of devastating ischemic events, such as stroke or central retinal artery occlusion.

Early Discontinuation of Antithrombotic Treatment Following Left Atrial Appendage Closure

Although antithrombotic treatment is recommended after left atrial appendage closure (LAAC), some patients require discontinuation of antithrombotic treatment after LAAC without evidence on the safety of such a strategy. We sought to evaluate outcomes of patients who had early antithrombotic treatment discontinuation after LAAC. This is a multicenter study including 1,082 patients who underwent successful LAAC. Early discontinuation of antithrombotic treatment was defined as discontinuation of all antiplatelet/anticoagulant treatment within 6months following the procedure. A propensity-matched analysis was used to compare outcomes of patients with and without early antithrombotic treatment discontinuation. A total of 148 patients (13.7%) had early antithrombotic treatment discontinuation. In the entire population, antithrombotic treatment discontinuation patients exhibited a lower CHA2DS2-VASc score (p <0.001) and a higher rate of previous gastrointestinal bleeding episodes (p=0.01) compared with patients without discontinuation. After a median follow-up of 2.1(1,1-3.1) years after antithrombotic treatment discontinuation, the rates of death, ischemic stroke, and major bleeding were 12.1, 0.6, and 3.3 per 100 patient-years. In 119 matched pairs with similar baseline characteristics, antithrombotic treatment discontinuation patients had a similar risk of death (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.65 to 1.71, p=0.82), ischemic stroke (HR 0.39, 95% CI 0.04 to 3.79, p=0.42) and major bleeding (HR 1.48, 95% CI 0.56 to 3.88, p=0.43) compared with those without discontinuation. In conclusion, antithrombotic treatment was discontinued in 1 of 7 selected patients within 6months after LAAC, and this was not associated with an increased risk of death or thromboembolic events after a median follow-up of 2years. These data support the safety of shorter periods of antithrombotic therapy after LAAC in high bleeding risk patients based on clinician judgment. Further trials are warranted.

Effect of early tirofiban administration on N-terminal pro-B-type natriuretic peptide level in patients treated with primary percutaneous coronary intervention.

To investigate the potential association between early tirofiban treatment and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level after primary percutaneous coronary intervention (PCI). Whether the use of adjunctive early glycoprotein IIb/IIIa inhibitors (GPIs) therapy, may affect the level of NT-proBNP after primary PCI is poorly studied. Nine hundred and eighty four ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI were randomized to either pre-hospital tirofiban administration or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18-96 hr after PCI. There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post-PCI. Post-PCI NT-proBNP level dichotomized with median value as cut-off (968.8 pg/mL, IQR 430.9-1970.0) was significantly lower in patients treated with early tirofiban as compared to placebo (45.5% vs. 54.2% P = 0.011). At multivariate logistic regression analysis, independent predictors of post-PCI NT-proBNP level above the median were: NT-proBNP baseline level (OR 5.19; 95% CI, 2.92-9.25, P < 0.001), Killip class>I (OR 4.07; 95% CI 1.24-13.36, P = 0.021), anterior infarct location (OR 2.61; 95% CI 1.84-3.70, P < 0.001), age (years) (OR 1.04; 95% CI 1.03-1.06, P < 0.001), male gender (OR 0.38; 95% CI 0.26-0.57, P < 0.001), prior PCI (OR 0.49; 95% CI 0.27-0.90, P = 0.021) and tirofiban administration (OR 0.71; 95% CI 0.51-0.99; P = 0.045). In a large cohort of STEMI patients, pre-hospital tirofiban administration was independently associate with a lower risk of high NT-proBNP level after primary PCI, supporting the potential benefit of early antithrombotic treatment administration in STEMI patients. The trial is registered under No. ISRCTN06195297.

Resumption of Antithrombotic Agents in Chronic Subdural Hematoma: A Systematic Review and Meta-analysis.

The clinical decision whether and when to resume antithrombotics in patients with chronic subdural hematomas (CSDH) postoperatively is limited by a lack of quality evidence exploring this topic. Our study aims to assess the available evidence of patient complication outcomes, specifically hemorrhagic and thromboembolic events, following the resumption or non-resumption of antithrombotic agents postoperatively in CSDH patients already on these agents before CSDH. We followed recommended PRISMA guidelines for systematic reviews. Electronic database searches were performed to identify included studies. Data were extracted and analyzed using meta-analysis. Eight studies were included for analysis. The most common indication for antithrombotic treatment before onset of CSDH was atrial fibrillation (29.6%), followed by prosthetic heart valve (16.6%), recent myocardial infarction (14.1%), prior stroke or transient ischemic attack (11.6%), and finally venous thromboembolism (8.3%). The overall hemorrhagic complication rate was 14.8% in the resumption group versus 18.6% in the no resumption group (P= 0.591). This did not differ between early (<2 weeks) versus late (>1 month) resumption (15% vs. 18.6%, P=0.97). The rate of thromboembolism however was statistically lower in those who resumed antithrombotics (2.9% vs. 6.8%, P<0.001). There was a non-significant trend towards higher thromboembolic rates with early resumption (5.3% vs. 2.1%, P= 0.23). The decision to resume antithrombotics postoperatively in the clinical management of CSDH patients is a complex one and should therefore be a highly individualized process. Our meta-analysis demonstrates that in selected cases, it is feasible to resume early antithrombotic treatment without additional hemorrhagic or thromboembolic risk.

Abstract 116: Relationship of Stroke Unit Status With Quality of Care and Outcome for Acute Stroke Patients: Results From China National Stroke Registry II

Introduction: A key element in modern stroke care is dedicated stroke units. However, it is unclear whether processes of acute ischemic stroke (AIS) care and outcomes are different between hospitals with and without stroke units in China. Methods: We analyzed the China National Stroke Registry II data from June 2012 to January 2013. Processes of care were examined by 13 individual national guideline-recommended indicators and composite score. Patients’ outcomes included all caused death, stroke recurrence, and disability (modified Rankin Score ≥3) at 3, 6 and 12month after discharge. Propensity score matching was used to balance the baseline characteristics. We used cox model with shared frailty model and logistic regression with generalized estimating equation to analysis the relationship between stroke units and clinical outcomes. Results: Among 19 604 AIS patients, there were 11050 (56.4%) patients in 121 hospitals with stroke units, and 8554 (43.6%) patients in 96 hospitals without stroke units. After matching, 8125 pairs of patients were analyzed. Totally, the composite score of processes was higher in hospitals with stroke units than that without(77% versus 74%, p&lt;0.05). Hospitals with stroke units were more likely to conduct anticoagulation for atrial fibrillation, early antithrombotic treatment, smoking cessation, and stroke education (Figure 1). However, there are no differences between patients in hospitals with and without stroke units in clinical outcomes(Table 1). Conclusions: Our study showed that processes of care of AIS were better in patients in hospitals with stroke units. However, patients in hospitals with stroke units didn’t performance differences in clinical outcomes after discharge.

Early antithrombotic treatment with warfarin oral suspension in severe neonatal protein C deficiency

Neonatal severe protein C deficiency is a serious disease. There is no uniform approach for long-term preventive treatment of thrombotic events. We report the case of neonatal severe protein C deficiency treated with warfarin oral suspension. An international normalized ratio (INR) from 2.5 to 3.5 was expected. The INR was measured by home monitoring using the Coaguchek XS® (Roche Diagnostics, Mannheim, Germany) monitor. During 2years of warfarin treatment, there were only two minor episodes of purpuric access and no bleeding was reported. This case suggests that the early introduction of warfarin oral suspension, home-care monitoring, and parental education programs may be a beneficial treatment option for children with protein C deficiency.

Abstract W P283: Race-Ethnic Stroke Disparities in the Florida-Puerto Rico Collaboration to Reduce Stroke Disparities Study - The NINDS Stroke Prevention Intervention Research Program

Background: Race-ethnic disparities in stroke care can contribute to inequality in stroke outcomes. We sought to determine the disparities in stroke performance metrics by race-ethnicity in a voluntary stroke registry of Florida and Puerto Rico Get With The Guidelines-Stroke (GWTG-S) data. Methods: Sixty-three sites who had enrolled in the FL-PR Stroke Registry (54 FL; 9 PR) recorded 38,684 ischemic stroke cases from 2010 to 2013. Generalized linear regression models were used to evaluate race-ethnic differences in 7 pre-defined acute stroke performance measures and defect-free care (IV tPA treatment, in-hospital antithrombotic therapy, DVT prophylaxis, antithrombotic therapy at discharge, anticoagulation therapy, statin medication at discharge, and smoking cessation counseling), adjusting for age and region (FL vs. PR). Results: Of acute ischemic stroke cases, 63% were non-Hispanic White (NHW), 18% NH-Black (NHB), and 17% Hispanic. The mean age was 71±14 years. NHW were older (73±14), followed by Hispanics (70±14), and NHB (63±14); p&lt;0.0001. Defect-free care was better among NHB (78%) and NHW (76%) than in Hispanics (68%), p&lt;0.0001. Defect-free care improved over time and the race-ethnic disparity decreased (2010: NHW 61%, NHB 64%, Hispanic 46%, p&lt;0.0001; 2013: 91%, 91%, 86%, p=0.47 respectively). NHW were most likely to receive IV tPA treatment (arrived by 2 hours and treated by 3 hours; 88%) and early antithrombotic treatment (96%). Hispanics were least likely to receive DVT prophylaxis (76%), anticoagulation (92%), statins (89%), and smoking cessation counseling (93%). Conclusions: Race-ethnic disparities in acute stroke care are evident yet decreasing, coinciding with improvements in quality of care over time in Florida and Puerto Rico hospitals participating in GWTG-S. Special stroke quality improvement programs to target areas where performance is less than expected and minimize race-ethnic disparities are necessary to improve stroke care for all Americans.

How long to anticoagulate?

Anticoagulant drugs have dramatically decreased the morbidity and mortality associated with venous thromboembolism (VTE). Although early antithrombotic treatment is straightforward, doubts still exist in the decision process of ‘how long to anticoagulate?’ It is common practice among physicians to stop anticoagulation in those who had one episode of VTE; deep vein thrombosis or pulmonary embolism (PE), after 3–6 months and recommend long-term anticoagulation in those who had a second event. Recent studies have however identified risk stratification models which could help in determining the duration of anticoagulation. The decision on the duration of anticoagulant treatment should be based on the balance between benefits of preventing a recurrent VTE episode and the risks of bleeding from the drugs. The first step in this regard is to identify if there has been a precipitating factor for the VTE. These commonly are surgery, periods of immobilization like after needing a plaster cast and hormonal treatments like oral contraceptive pill. In these patients, the risk of VTE recurrence is ∼5% in the first year after stopping anticoagulant therapy. The latest American College of Chest Physicians guidance on VTE management consider this risk to be low enough to discontinue anticoagulant therapy at the end of 3 months.1,2 The only practical point in this scenario is how confidently the precipitating factor can be linked to the VTE event. For example, if the thrombotic episode occurred more than 3 months after the surgery, can this be considered as a provoked event? If the female develops a PE after being on the …

Circulation Editors’ Picks

<i>Circulation</i> Editors’ Picks

Admission International Normalized Ratio Levels, Early Treatment Strategies, and Major Bleeding Risk Among Non–ST-Segment–Elevation Myocardial Infarction Patients on Home Warfarin Therapy

Background— Non–ST-segment–elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non–ST-segment–elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population. Methods and Results— We stratified 5787 non–ST-segment–elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR &lt;2), therapeutic (INR, 2–3), and supratherapeutic (INR &gt;3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03–1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30–1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR ≥2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14–1.72] for heparin; 1.50 [95% CI, 1.22–1.84] for clopidogrel; and 1.82 [95% CI, 1.43–2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86–1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding. Conclusions— National patterns of early antithrombotic treatment for non–ST-segment–elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Aspirin resistance after coronary artery bypass grafting.

The antiplatelet effect of aspirin may be compromised by an enhanced platelet turnover, generating an increased fraction of platelets that is able to form thromboxane within the dosing intervals (usually 1 day). This may be of particular relevance for patients undergoing CABG after cardiopulmonary bypass, when postoperative platelet turnover is increased. The present work examines whether the antiplatelet effect of aspirin, which is based on the inhibition of platelet thromboxane production, may be impaired by an increased platelet turnover. Determination of thromboxane in collagen-stimulated platelet-rich plasma after CABG showed a remarkable enhancement of the capacity for thromboxane formation, despite the fact that aspirin was administered at an antiplatelet dose (100 mg once daily) that largely suppressed thromboxane synthesis in healthy control subjects. Aspirin is widely used to reduce graft thrombosis after coronary artery bypass grafting (CABG).1 However, aspirin appears to not always be an effective inhibitor of platelet function because considerable individual variations in the antiplatelet effect of aspirin have been reported in patients assigned to CABG.2 ASPIRIN RESISTANCE AFTER CORONARY ARTERY BYPASS GRAFTING

Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials.

A formal statistical overview of all truly randomised trials was undertaken to determine whether antithrombotic therapy is effective and safe in the early treatment of patients with acute stroke. There were 15 completed randomised controlled trials of the value of early antithrombotic treatment in patients with acute stroke. The regimes tested in acute presumed or confirmed ischaemic stroke were: heparin, 10 trials with 1047 patients: oral anticoagulants, one trial with 51 patients: antiplatelet therapy, three trials with 103 patients. Heparin was tested in one trial with 46 patients with acute haemorrhagic stroke. Outcome measures were deep venous thrombosis (confirmed by I125 scanning or venography), pulmonary embolism, death from all causes, haemorrhagic transformation of cerebral infarction, level of disability in survivors. In patients with acute ischaemic stroke, allocation to heparin was associated with a highly significant 81% (SD 8, 2p 0.1). There were relatively few deaths in the trials in patients with presumed ischaemic stroke: 94/485 (19.4%) among patients allocated to the control group vs 79/497 (15.9%) among patients who were allocated heparin. The observed 18% (SD 16) reduction in the odds of death was not statistically significant. The least biased estimated of the effect of treatment on haemorrhagic transformation of the cerebral infarct (HTI) comes from trials where all patients were scanned at the end of treatment, irrespective of clinical deterioration; using this analysis, haemorrhagic transformation occurred in 7/102 (6.9%) control vs 8/106 (7.5%) treated, a non-significant 12% increase (SD 56, 2p > 0.1). These data cannot exclude the possibility that heparin substantially increases the risks of HTI. No data on disability in survivors could be obtained. Early heparin treatment might be associated with substantial reductions in deep venous thrombosis (and probably also pulmonary embolism) and possibly a one fifth reduction in mortality (equivalent to the avoidance of 20-40 early deaths per thousand patients treated.) However, the data were wholly inadequate on safety, particularly on the risk of haemorrhagic transformation of the infarct and on the hazards of heparin therapy in patients with known intracerebral haemorrhage. The trials of oral anticoagulants (15 deaths among 57 patients) and antiplatelet therapy (two deaths among 103 patients) were too small to be informative. Much larger randomized trials-comparing aspirin, heparin and the combination of both drugs against control-in patients with acute ischaemic stroke are justified (and several are now planned or underway).