Precision of VerifyNow P2Y12 Assessment of Clopidogrel Response in Patients Undergoing Cerebral Aneurysm Flow Diversion

Abstract Background Dual antiplatelet therapy (DAT), most commonly with aspirin and Clopidogrel, is the standard of care for intracranial stenting, including flow diversion. Clopidogrel response varies by individual. Objective To investigate the real-world precision of VerifyNow P2Y12 assessment (Accumetrics, San Diego, California) of Clopidogrel response. Methods Using a prospectively-collected, IRB-approved cerebral aneurysm database 643 patients were identified who were treated with the Pipeline embolization device from 2011 to 2017. Patients with multiple P2Y12 assays drawn within a 24-h window were identified. A single patient could contribute multiple, independent sets. Levels drawn before a 5-d course of DAT and patients who received alternative antiplatelet agents were excluded. Therapeutic range was defined as platelet reaction units (PRU) 60–200. Results A total of 1586 P2Y12 measurements were recorded; 293 (46%) patients had more than one assay. One hundred forty (22%) patients had multiple P2Y12 measurements within 24 h. These patients accounted for 230 independent 24-h sets. The average P2Y12 fluctuation across all sets was 35 points; the 25th, 50th, and 75th percentiles were 12, 26, and 48 points, respectively. Of the 230 24-h sets of P2Y12 assays, 76% remained within their original therapeutic category: 100 (43%) all therapeutic, 54 (23%) all hypo-responsive, and 21 (9%) all hyper-responsive. Twenty-four percent of patients fluctuated between therapeutic categories when multiple P2Y12 assessments were drawn within a 24-h period: 29 (13%) between hypo-response and therapeutic, 23 (10%) between hyper-response and therapeutic, and 3 (1%) between hypo-response and hyper-response. CONCLUSION Our experience suggests P2Y12 is an often-imprecise measure, and this should be considered when utilizing P2Y12 levels for clinical decisions.

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Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series

The Canadian Journal of Hospital Pharmacy ◽

10.4212/cjhp.v71i6.2849 ◽

2019 ◽

Vol 71 (6) ◽

Author(s):

Jodi R DeGrote ◽

Elizabeth M Olafson ◽

Alexander Drofa ◽

Evgueni Kouznetzov ◽

Michael Manchak ◽

...

Keyword(s):

Ischemic Stroke ◽

Acetylsalicylic Acid ◽

Cerebral Aneurysm ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Case Series ◽

Bleeding Complications ◽

Attractive Alternative ◽

Pipeline Embolization Device ◽

End Point

ABSTRACT Background: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a P2Y12-receptor antagonist is often used to prevent thrombotic complications after placement of a Pipeline embolization device (PED) for cerebral aneurysm. Although clopidogrel is common in this setting, high rates of nonresponse to this drug have made ticagrelor a potentially attractive alternative. Objective: To describe safety and efficacy outcomes for ticagrelor following PED placement, including measurement of platelet function. Methods: A retrospective analysis of data was completed for patients who underwent PED placement for cerebral aneurysm at a single centre between November 2015 and March 2017, with subsequent prescription of ticagrelor and ASA as dual antiplatelet therapy. The primary end point was any ischemic stroke or death within 1 year after the procedure. Intracranial hemorrhage was a secondary end point. Additionally, measurement of and values for platelet reactivity units (PRUs) during receipt of ticagrelor and ASA were evaluated. Results: A total of 29 patients were included in this retrospective study. One patient experienced ischemic stroke 226 days after placement of the PED. In addition, 3 patients died during the 1-year follow-up period for causes unrelated to stroke or bleeding complications. No cases of intra -cranial hemorrhage were observed. Samples for measurement of P2Y12 levels were drawn at the discretion of the neurointerventionalists, and the PRU value was measured at least once for 28 (97%) of the 29 patients. The mean number of PRU measurements per patient after initiation of ticagrelor was 2.1 (standard deviation [SD] 1). Mean PRU value after initiation of ticagrelor was 65 (SD 57). Conclusions: In this case series describing the use of ticagrelor and ASA as dual antiplatelet therapy after PED placement for cerebral aneurysm, there was just one ischemic stroke, which occurred after the dual antiplatelet therapy had been discontinued. Further prospective trials are needed to describe the utility of ticagrelor use after PED placement, as well as its dosing and monitoring.RÉSUMÉContexte : Une bithérapie antiplaquettaire composée d’acide acétylsali-cylique (AAS) et d’un inhibiteur du récepteur P2Y12 est fréquemment utilisée pour prévenir les complications thrombotiques après la mise en place d’un dispositif d’embolisation Pipeline pour traiter un anévrisme cérébral. Quoique le clopidogrel soit souvent utilisé dans ce contexte, des taux élevés d’absence de réponse à ce médicament ont fait du ticagrélor une solution de rechange potentiellement intéressante. Objectif : Décrire les résultats relatifs à la sécurité et à l’efficacité du ticagrélor après la mise en place d’un dispositif d’embolisation, y compris l’analyse de la fonction plaquettaire. Méthodes : Une analyse rétrospective de données a été réalisée dans un seul centre entre novembre 2015 et mars 2017 à l’aide des dossiers médicaux de patients chez qui a été posé un dispositif d’embolisation Pipeline comme traitement pour un anévrisme cérébral et à qui a ensuite été prescrite une bithérapie antiplaquettaire de ticagrélor et d’AAS. Le critère d’évaluation principal était les cas d’infarctus cérébral ou de décès durant l’année suivant l’opération. Les cas d’hémorragie intracrânienne ont servi de critère d’évaluation secondaire. De plus, l’analyse a porté sur l’évaluation de la réactivité plaquettaire et sa quantification en unités de réaction au P2Y12 pendant la prise de ticagrélor et d’AAS. Résultats : Au total, 29 patients ont été admis à la présente étude rétrospective. Un patient a subi un infarctus cérébral 226 jours après la mise en place d’un dispositif d’embolisation Pipeline. De plus, 3 patients sont décédés au cours de la période de suivi d’un an en raison de causes sans lien avec des complications liées à un accident vasculaire cérébral ou à une hémorragie. Aucun cas d’hémorragie intracrânienne n’a été observé. Les échantillons destinés à la mesure des unités de réaction au P2Y12 ont été prélevés selon le jugement des neuro-intervenants et l’évaluation de la réactivité plaquettaire a été réalisée au moins une fois chez 28 (97 %) des 29 patients. Le nombre moyen de mesures des unités de réaction au P2Y12 par patient était de 2,1 (écart-type de 1). Après l’amorce d’un traitement par ticagrélor, le résultat moyen en unités de réaction au P2Y12 était de 65 (écart-type de 57).Conclusions : Dans la présente série de cas décrivant l’utilisation d’une bithérapie antiplaquettaire composée de ticagrélor et d’AAS après la mise en place d’un dispositif d’embolisation Pipeline comme traitement pour un anévrisme cérébral, seul un cas d’infarctus cérébral a été observé et il s’est produit après l’arrêt de la bithérapie antiplaquettaire. De plus amples études prospectives sont nécessaires pour décrire l’utilité et la posologie du ticagrélor ainsi que le suivi du traitement après la mise en place d’un dis-positif d’embolisation Pipeline.

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Abstract 15510: Trials of Dual Antiplatelet Therapy Do Not Include Evidence-Based Strategies for Gastrointestinal Bleeding Prevention

Circulation ◽

10.1161/circ.142.suppl_3.15510 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jacob E Kurlander ◽

Geoffrey Barnes ◽

Devraj Sukul ◽

Danielle Helminski ◽

Alex Kokaly ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Standard Of Care ◽

Coronary Intervention ◽

Flow Diagram ◽

Clinical Trial Registries ◽

Study Protocols ◽

Registration Number ◽

Hemorrhagic Risk

Background: Proton pump inhibitors (PPIs) substantially reduce the risk of upper gastrointestinal bleeding (GIB) and are recommended for high-risk patients by professional cardiology societies but remain underused in clinical practice. By reducing hemorrhagic risk associated with dual antiplatelet therapy (DAPT), PPIs may affect the risk-benefit equation of varying durations of DAPT and should be considered in such clinical trials. We sought to determine the extent to which randomized controlled trials (RCTs) evaluating DAPT after percutaneous coronary intervention (PCI) provide guidance on the use of PPIs for GIB prevention. Methods: A previously completed systematic review was updated to identify all RCTs comparing varying durations of DAPT between June 1983 and October 2019. Primary publications, online supplements, clinical trial registries and additional publications linked to the trial registration number were reviewed for protocol information. Results: Of 21 included studies (n=58,625; Figure), none of the study protocols provided guidance on the use of PPIs by trial participants. One study stated that the decision to use PPIs was left to the discretion of the treating physician. Two studies specified that treating physicians could prescribe non-mandated medications concordant with standard of care but did not specifically mention PPIs. Only 5 studies reported rates of PPI use, which ranged from 25.6-69.1%. Conclusions: Trials of DAPT regimens did not provide guidance on the use of PPI gastroprotection, a guideline-supported strategy for prevention of bleeding from the GI tract, the most common site of bleeding in patients using DAPT. Guidance on and reporting of PPI use should be mandatory in future antithrombotic trials to enhance their safety and interpretability. Figure 1. PRISMA flow diagram

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Very delayed discontinuation of telescoped Pipeline embolization devices: a case report

Interventional Neuroradiology ◽

10.1177/1591019918809932 ◽

2018 ◽

Vol 25 (2) ◽

pp. 182-186

Author(s):

Manoj Bohara ◽

Kosuke Teranishi ◽

Kenji Yatomi ◽

Takashi Fujii ◽

Takayuki Kitamura ◽

...

Keyword(s):

Internal Carotid ◽

Flow Diversion ◽

Total Occlusion ◽

Pipeline Embolization Device ◽

Complete Occlusion ◽

Radiological Features ◽

Long Term Follow Up ◽

Aneurysm Occlusion

Background Flow diversion with the Pipeline embolization device (PED) is a widely accepted treatment modality for aneurysm occlusion. Previous reports have shown no recanalization of aneurysms on long-term follow-up once total occlusion has been achieved. Case description We report on a 63-year-old male who had a large internal carotid artery cavernous segment aneurysm. Treatment with PED resulted in complete occlusion of the aneurysm. However, follow-up angiography at four years revealed recurrence of the aneurysm due to disconnection of the two PEDs placed in telescoping fashion. Conclusion Herein, we present the clinico-radiological features and discuss the possible mechanisms resulting in the recanalization of aneurysms treated with flow diversion.

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Clopidogrel Resistance: Current Issues

Journal of Enam Medical College ◽

10.3329/jemc.v6i1.26381 ◽

2016 ◽

Vol 6 (1) ◽

pp. 38-46

Author(s):

NS Neki

Keyword(s):

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Ex Vivo ◽

Platelet Reactivity ◽

Antiplatelet Agents ◽

Clinical Problem ◽

Coronary Intervention ◽

Platelet Activity ◽

Clopidogrel Resistance ◽

Underlying Mechanisms

Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance.J Enam Med Col 2016; 6(1): 38-46

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Abstract WP283: The Multiple-Encounter Multiply-Thrombolysed Telestroke Patient - A Unique Patient Population

Stroke ◽

10.1161/str.51.suppl_1.wp283 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Johanna L Morton ◽

Diamond K Northington ◽

B. Tilman Jolly

Keyword(s):

Patient Population ◽

Stroke Risk ◽

Standard Of Care ◽

Psychiatric Disease ◽

Outcome Analysis ◽

Single Patient ◽

Discharge Data ◽

Stroke Risk Factors ◽

Inherent Risk ◽

Patient Database

Background: Thrombolysis with alteplase is the standard of care for the treatment of eligible patients presenting with acute ischemic stroke (AIS). Many hospitals do not have access to in-person cerebrovascular expertise, and utilize telestroke services for the remote diagnosis and treatment of AIS. Through this practice, an unusual subset of patients with multiple presentations having received thrombolysis several times has emerged. This study describes the largest known sample of this multiple-encounter population within a single teleneurology practice spanning 39 states over 4 years. Methods: A retrospective observational study of the experience of a single teleneurology practice serving over 400 hospitals from July 1, 2015 to June 30, 2019 was performed. The alteplase patient database was queried to identify patients with both multiple telestroke and multiple alteplase encounters. Demographic and clinical data were abstracted. Outcome analysis was restricted to those patients with available complete discharge data. Results: Within the queried period, 71 patients were identified to have had multiple encounters with the teleneurology practice, 46 males and 25 females. Of these, 36 patients were seen twice, 18 were seen three times, 10 were seen four times, and 7 had five or more encounters, with the maximum number of encounters of 26. Seven patients received care in multiple states. The overall alteplase rate was 58.2%. Alteplase was administered on more than one encounter in all 71 patients, with a maximum alteplase administration of 4 times in a single patient. The median NIHSS score in this population was 5. Of the 71 patients, all had stroke risk factors, 36.6% had noncerebrovascular neurological comorbidities, and 36.6% had psychiatric disease history. The symptomatic hemorrhage rate in this population was 0%. Conclusion: The observed phenomena of recurrent teleneurology encounters for patients presenting with suspected AIS symptoms and receiving alteplase at increased rates is not well-described and is poorly understood. Given the inherent risk and resource utilization associated with thrombolysis, further analysis of the characteristics of this patient population is warranted.

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Impact of Diabetes Mellitus on Antithrombotic Management Patterns and Long‐Term Clinical Outcomes in Patients With Acute Coronary Syndrome: Insights From the EPICOR Asia Study

Journal of the American Heart Association ◽

10.1161/jaha.119.013476 ◽

2020 ◽

Vol 9 (22) ◽

Cited By ~ 1

Author(s):

Shaoyi Guan ◽

Xiaoming Xu ◽

Yi Li ◽

Jing Li ◽

Mingzi Guan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Acute Coronary Syndrome ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Antiplatelet Agents ◽

Coronary Syndrome ◽

Increased Risk ◽

Antithrombotic Management

Background Long‐term use of antiplatelet agents after acute coronary syndrome in diabetic patients is not well known. Here, we describe antiplatelet use and outcomes in such patients enrolled in the EPICOR Asia (Long‐Term Follow‐up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients in Asia) registry. Methods and Results EPICOR Asia is a prospective, observational study of 12 922 patients with acute coronary syndrome surviving to discharge, from 8 countries/regions in Asia. The present analysis included 3162 patients with diabetes mellitus (DM) and 9602 patients without DM. The impact of DM on use of antiplatelet agents and events (composite of death, myocardial infarction, and stroke, with or without any revascularization; individual components, and bleeding) was evaluated. Significant baseline differences were seen between patients with DM and patients without DM for age, sex, body mass index, cardiovascular history, angiographic findings, and use of percutaneous coronary intervention. At discharge, ≈90% of patients in each group received dual antiplatelet therapy. At 2‐year follow‐up, more patients with DM tended to still receive dual antiplatelet therapy (60% versus 56%). DM was associated with increased risk from ischemic but not major bleeding events. Independent predictors of the composite end point of death, myocardial infarction, and stroke in patients with DM were age ≥65 years and use of diuretics at discharge. Conclusions Antiplatelet agent use is broadly comparable in patients with DM and patients without DM, although patients with DM are more likely to be on dual antiplatelet therapy at 2 years. Patients with DM are at increased risk of ischemic events, suggesting an unmet need for improved antithrombotic treatment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01361386.

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DUAL ANTIPLATELET THERAPY IN ACUTE CORONARY SYNDROMES: IDENTIFYING FACTORS RESPONSIBLE FOR THE STAGNATION IN THE USE OF NOVEL ANTIPLATELET AGENTS IN A UNIVERSITY TERTIARY CARE CENTER

Canadian Journal of Cardiology ◽

10.1016/j.cjca.2016.07.173 ◽

2016 ◽

Vol 32 (10) ◽

pp. S117-S118

Author(s):

H. Racine ◽

M. Roy ◽

M. Charron-Giguère ◽

J. Dery

Keyword(s):

Antiplatelet Therapy ◽

Acute Coronary Syndromes ◽

Dual Antiplatelet Therapy ◽

Care Center ◽

Tertiary Care ◽

Antiplatelet Agents ◽

Tertiary Care Center ◽

Coronary Syndromes

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A2, M2, P2 aneurysms and beyond: results of treatment with pipeline embolization device in 65 patients

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2018-014631 ◽

2019 ◽

Vol 11 (9) ◽

pp. 903-907 ◽

Cited By ~ 9

Author(s):

Christopher T Primiani ◽

Zeguang Ren ◽

Peter Kan ◽

Ricardo Hanel ◽

Vitor Mendes Pereira ◽

...

Keyword(s):

Clinical Outcome ◽

Cerebral Artery ◽

Intracranial Aneurysms ◽

Flow Diversion ◽

Vascular Pathology ◽

Parent Vessel ◽

Rare Type ◽

Pipeline Embolization Device ◽

Aneurysm Size

BackgroundIntracranial aneurysms located in the distal vessels are rare and remain a challenge to treat through surgical or endovascular interventions.ObjectiveTo describe a multicenter approach with flow diversion using the pipeline embolization device (PED) for treatment of distal intracranial aneurysms.MethodsCases of distal intracranial aneurysms defined as starting on or beyond the A2 anterior cerebral artery, M2 middle cerebral artery, and P2 posterior cerebral artery segments were included in the final analysis.Results65 patients with distal aneurysms treated with the PED were analyzed. Median aneurysm size at the largest diameter was 7.0 mm, 60% were of a saccular morphology, and 9/65 (13.8%) patients presented in the setting of acute rupture. Angiographic follow-up data were available for 53 patients, with a median follow-up time of 6 months: 44/53 (83%) aneurysms showed complete obliteration, 7/53 (13.2%) showed reduced filling, and 2/53 (3%) showed persistent filling. There was no association between patient characteristics, including aneurysm size (P=0.36), parent vessel diameter (P=0.27), location (P=0.81), morphology (P=0.63), ruptured status on admission (P=0.57), or evidence of angiographic occlusion at the end of the embolization procedure (P=0.49). Clinical outcome data were available for 60/65 patients: 95% (57/60) had good clinical outcome (modified Rankin Scale score of 0–2) at 3 months.ConclusionsThis large multicenter study of patients with A2, M2, and P2 distal aneurysms treated with the PED showed that flow diversion may be an effective treatment approach for this rare type of vascular pathology. The procedural compilation rate of 7.7% indicates the need for further studies as the flow diversion technology constantly evolves.

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Flow Diversion for Treatment of Intracranial Aneurysms in Pediatric Patients: Multicenter Case Series

Neurosurgery ◽

10.1093/neuros/nyz380 ◽

2019 ◽

Vol 87 (1) ◽

pp. 53-62

Author(s):

Jacob Cherian ◽

Visish Srinivasan ◽

Michael T Froehler ◽

Jonathan A Grossberg ◽

C Michael Cawley ◽

...

Keyword(s):

Clinical Outcomes ◽

Intracranial Aneurysms ◽

Case Series ◽

Flow Diversion ◽

Pipeline Embolization Device ◽

Patient Demographics ◽

Scale Scores ◽

Treatment Considerations ◽

Device Placement ◽

Aneurysm Occlusion

Abstract BACKGROUND Though the Pipeline Embolization Device (Medtronic) is approved for use in adults 22 yr and older, the high efficacy and long-term durability of the device is attractive for treatment of intracranial aneurysms in younger patients who often have aneurysms less amenable to traditional endovascular treatments. OBJECTIVE To report technical, angiographic, and clinical outcomes in patients aged 21 or below undergoing flow-diversion treatment for intracranial aneurysms. METHODS Retrospective review across 16 institutions identified 39 patients aged 21 or below undergoing 46 treatment sessions with Pipeline Embolization Device placement between 2012 and 2018. A total of 50 intracranial aneurysms were treated. Details regarding patient demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed in a multicenter database. RESULTS A total of 70% of patients were male. Nonsaccular morphology was seen in half of identified aneurysms. Six aneurysms were giant, and five patients were treated acutely after ruptured presentation. Eight patients were younger than 10 yr of age. Complete aneurysm occlusion was seen in 74% of treated aneurysms. Three aneurysms (6%) were retreated. A total of 83% of patients had a modified Rankin Scale scores of ≤2 at last clinical follow-up. There were 2 early mortalities (4.3%) in the immediate postprocedure period because of rerupture of a treated ruptured aneurysm. No recanalization of a previously occluded aneurysm was observed. CONCLUSION Flow-diversion treatment is a safe and effective treatment for intracranial aneurysms in patients younger than 22 yr. Rates of complete aneurysm occlusion and adverse events are comparable for rates seen in older patients.

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