High on-treatment platelet reactivity – definition and measurement

2013 ◽  
Vol 109 (05) ◽  
pp. 792-798 ◽  
Author(s):  
Marco Cattaneo
Keyword(s):  
At Risk ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Antiplatelet Drug ◽  
Major Adverse Cardiovascular Events ◽  
Poor Responders ◽  
Patient Response ◽  
Increased Risk ◽  
Patients At Risk

SummaryIn the last decade, several studies revealed inter-patient response variability to antiplatelet agents: patients who display negligible or no responses to these drugs are considered poor responders, or “resistant” to treatment. In order to identify poor responders to an antiplatelet drug, laboratory tests of platelet function that specifically explore the platelet activation pathway that is targeted by the drug should be utilised. In addition, they should be performed both at baseline and during treatment: however, most studies explored platelet function during antiplatelet treatment, in order to identify those patients with “high on-treatment platelet reactivity” (HPR), which exposes them to increased risk of major adverse cardiovascular events (MACE). Many tests of platelet function have been used, most of which are able to identify patients at risk of MACE. Unfortunately, universal cut-off values for HPR have not been clearly established yet. In addition, the concordance among different tests in the identification of patients at risk is very poor and the most effective and safe treatment for patients at risk is still unknown.

Monitoring of antiplatelet therapy

2011 ◽  
Vol 31 (01) ◽  
pp. 41-51 ◽  
Author(s):  
H. Seidel ◽  
M. M. Rahman ◽  
R. E. Scharf
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
High Sensitivity ◽  
Antiplatelet Agents ◽  
Daily Practice ◽  
Adenosine Diphosphate ◽  
Poor Responders ◽  
Platelet Aggregometry

SummaryScreening of platelet function can be performed by point-of-care testing followed by platelet aggregometry in response to agonists such as collagen, adenosine diphosphate, epinephrine, and arachidonic acid. Despite in use for decades, this technique is not well standardized. Monitoring of antiplatelet therapy is increasingly applied in patients at high risk for re-thrombosis or bleeding. To assess pharmacological inhibition of platelet function, agonist-induced platelet aggregation, thromboxane B2 (TxB2) and vasodilator-stimulated protein phosphorylation (VASP) are being measured. While serum TxB2 levels of < 2 ng/ml reflect aspirin-induced inhibition of cyclo-oxygenase-1 activity with high sensitivity, VASP exhibits a wide variability upon treatment with clopidogrel or prasugrel. Multiple studies reveal an association between high residual platelet reactivity and adverse cardiovascular events in patients on antiplatelet therapy. However, despite the plethora of platelet function assays currently under investigation, their use in daily practice cannot be recommended. This is due to several reasons: (i) there is no consensus on the method and a respective cut-off value associated with clinical adverse outcome, and (ii) data demonstrating any benefit of tailored antiplatelet therapy and its monitoring (based on assessment of platelet functions) are still limited. Thus, appropriate identification of ‘resistant’ or ‘poor responders’ to antiplatelet agents remains challenging in clinical practice.

scholarly journals MicroRNA as Biomarkers for Platelet Function and Maturity in Patients with Cardiovascular Disease

2021 ◽  
Author(s):  
Oliver Buchhave Pedersen ◽  
Erik Lerkevang Grove ◽  
Steen Dalby Kristensen ◽  
Peter H. Nissen ◽  
Anne-Mette Hvas
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Function ◽  
Assessment Tool ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Quality Assessment Tool ◽  
Treatment And Prevention ◽  
Increased Risk ◽  
Meta Analyses ◽  
Potential Use

AbstractPatients with cardiovascular disease (CVD) are at increased risk of suffering myocardial infarction. Platelets are key players in thrombus formation and, therefore, antiplatelet therapy is crucial in the treatment and prevention of CVD. MicroRNAs (miRs) may hold the potential as biomarkers for platelet function and maturity. This systematic review was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To identify studies investigating the association between miRs and platelet function and maturity in patients with CVD, PubMed and Embase were searched on October 13 and December 13, 2020 without time boundaries. Risk of bias was evaluated using a standardized quality assessment tool. Of the 16 included studies, 6 studies were rated “good” and 10 studies were rated “fair.” In total, 45 miRs correlated significantly with platelet function or maturity (rho ranging from –0.68 to 0.38, all p < 0.05) or differed significantly between patients with high platelet reactivity and patients with low platelet reactivity (p-values ranging from 0.0001 to 0.05). Only four miRs were investigated in more than two studies, namely miR-223, miR-126, miR-21 and miR-150. Only one study reported on the association between miRs and platelet maturity. In conclusion, a total of 45 miRs were associated with platelet function or maturity in patients with CVD, with miR-223 and miR-126 being the most frequently investigated. However, the majority of the miRs were only investigated in one study. More data are needed on the potential use of miRs as biomarkers for platelet function and maturity in CVD patients.

scholarly journals Risk of colonoscopic post-polypectomy bleeding in patients on single antiplatelet therapy: systematic review with meta-analysis

2022 ◽  
Author(s):  
Marco Valvano ◽  
Stefano Fabiani ◽  
Marco Magistroni ◽  
Antonio Mancusi ◽  
Salvatore Longo ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Disease Recurrence ◽  
Major Adverse Cardiovascular Events ◽  
Control Group ◽  
P2y12 Inhibitors ◽  
Randomized Controlled ◽  
Electronic Search ◽  
Increased Risk

Abstract Background It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. Methods A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. Results Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37–3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40–14.00) and delayed PPB (OR 10.80; CI 4.63–25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. Conclusions Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.

scholarly journals Identifying those at risk of reattendance at discharge from emergency departments using explainable machine learning

2020 ◽  
Author(s):  
F. P. Chmiel ◽  
M. Azor ◽  
F. Borca ◽  
M. J. Boniface ◽  
D. K. Burns ◽  
...  
Keyword(s):  
Machine Learning ◽  
At Risk ◽  
Emergency Departments ◽  
Risk Groups ◽  
Machine Learning Algorithms ◽  
Care Indicator ◽  
Number Of Patients ◽  
Increased Risk ◽  
Single Centre Study ◽  
Patients At Risk

ABSTRACTShort-term reattendances to emergency departments are a key quality of care indicator. Identifying patients at increased risk of early reattendance can help reduce the number of patients with missed or undertreated illness or injury, and could support appropriate discharges with focused interventions. In this manuscript we present a retrospective, single-centre study where we create and evaluate a machine-learnt classifier trained to identify patients at risk of reattendance within 72 hours of discharge from an emergency department. On a patient hold-out test set, our highest performing classifier obtained an AUROC of 0.748 and an average precision of 0.250; demonstrating that machine-learning algorithms can be used to classify patients, with moderate performance, into low and high-risk groups for reattendance. In parallel to our predictive model we train an explanation model, capable of explaining predictions at an attendance level, which can be used to help inform the design of interventional strategies.

scholarly journals Platelet-reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta-analysis

2014 ◽  
Vol 12 (5) ◽  
pp. 736-747 ◽  
Author(s):  
P. P. Wisman ◽  
M. Roest ◽  
F. W. Asselbergs ◽  
P. G. de Groot ◽  
F. L. Moll ◽  
...  
Keyword(s):  
Systematic Review ◽  
At Risk ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Patients At Risk

Abstract 119: Risk of Intracerebral Hemorrhage with Combined Antiplatelet and Anticoagulant Use

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Matthew L Flaherty ◽  
Lili Ding ◽  
Jessica G Woo ◽  
Lisa Martin ◽  
Mary Haverbusch ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Antiplatelet Agents ◽  
Population Based ◽  
Careful Consideration ◽  
Antiplatelet Drug ◽  
Treatment Groups ◽  
Stroke Study ◽  
Increased Risk ◽  
Anticoagulant Drugs ◽  
Increase Risk

Context: Intracranial bleeding is the most feared complication of antithrombotic use. Antiplatelet and anticoagulant drugs increase risk of intracerebral hemorrhage (ICH), yet in some instances, combinations of antiplatelet agents and anticoagulants are used without firm evidence of efficacy. Few studies have compared the risks of different agents and their combinations in a single population. We determined the risk of ICH associated with the most commonly used antiplatelet and anticoagulant drugs and their combinations in a population-based case-control study. Methods: This report includes data from subjects recruited from the Greater Cincinnati/Northern Kentucky area by the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study from 1997 to 2009. We compared individuals in different treatment groups to identify any differences in baseline covariates that could be associated with treatment assignment. As there were a number of statistically significant differences, we used multivariate matching to analyze risk for ICH conferred by different antithrombotic agents. Treatment effects on ICH were estimated using the matched samples while accounting for the dependence between matched individuals. Results: There were 733 subjects with ICH and 2555 controls included in this study period. Results are shown in the table. Use of aspirin, clopidogrel, or their combination was associated with a trend toward increased risk. Warfarin increased risk compared with no antithrombotic use (OR 3.98, p < 0.0001). The combination of warfarin and either aspirin or clopidogrel produced the greatest risk, compared with no antithrombic therapy (OR 4.92 p<0.001) or compared with warfarin alone (OR 3.00 p=0.009). Conclusions: The combination of warfarin and an antiplatelet drug significantly increases risk of ICH compared with no antithrombotic therapy or warfarin monotherapy. The use of combination therapy requires careful consideration in clinical practice.

A multiparametric ICD algorithm for heart failure risk stratification and management: an analysis in clinical practice

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
L Calo" ◽  
V Bianchi ◽  
D Ferraioli ◽  
L Santini ◽  
A Dello Russo ◽  
...  
Keyword(s):  
Heart Failure ◽  
At Risk ◽  
Clinical Practice ◽  
Risk Stratification ◽  
Management Strategies ◽  
Cardiac Resynchronization ◽  
Office Visits ◽  
Increased Risk ◽  
Patients At Risk ◽  
Observation Period

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The HeartLogic algorithm combines multiple implantable cardioverter defibrillator (ICD) sensors to identify patients at risk of heart failure (HF) events. Purpose We sought to evaluate the risk stratification ability of this algorithm in clinical practice. We also analyzed the alert management strategies adopted in the study group and their association with the occurrence of HF events. Methods The HeartLogic feature was activated in 366 ICD and cardiac resynchronization therapy ICD patients at 22 centers. The HeartLogic algorithm automatically calculates a daily HF index and identifies periods IN or OUT of an alert state on the basis of a configurable threshold (in this analysis set to 16). Results The HeartLogic index crossed the threshold value 273 times (0.76 alerts/patient-year) in 150 patients over a median follow-up of 11 months [25-75 percentile: 6-16]. Overall, the time IN the alert state was 11% of the total observation period. Patients experienced 36 HF hospitalizations and 8 patients died of HF (rate: 0.12 events/patient-year) during the observation period. Thirty-five events were associated with the IN alert state (0.92 events/patient-year versus 0.03 events/patient-year in the OUT of alert state). The hazard ratio in the IN/OUT of alert state comparison was (HR: 24.53, 95% CI: 8.55-70.38, p &lt; 0.001), after adjustment for baseline clinical confounders. Alerts followed by clinical actions were associated with a lower rate of HF events (HR: 0.37, 95% CI: 0.14-0.99, p = 0.047). No differences in event rates were observed between in-office and remote alert management. By contrast, verification of HF symptoms during post-alert examination was associated with a higher risk of HF events (HR: 5.23, 95% CI: 1.98-13.83, p &lt; 0.001). Conclusions This multiparametric ICD algorithm identifies patients during periods of significantly increased risk of HF events. The rate of HF events seemed lower when clinical actions were undertaken in response to alerts. Extra in-office visits did not seem to be required in order to effectively manage HeartLogic alerts, while post-alert verification of symptoms seemed useful in order to better stratify patients at risk of HF events.

Abstract 15714: Prediction of Sudden Cardiac Death With Automated High-Throughput Analysis of T-Wave Heterogeneity in Standard 12-Lead Electrocardiogram

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tuomas Kenttä ◽  
Bruce D Nearing ◽  
Kimmo Porthan ◽  
Jani T Tikkanen ◽  
Matti Viitasalo ◽  
...  
Keyword(s):  
At Risk ◽  
Relative Risk ◽  
Sudden Cardiac Death ◽  
General Population ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Adjusted Relative Risk ◽  
T Wave ◽  
Increased Risk ◽  
Patients At Risk

Introduction: Noninvasive identification of patients at risk for sudden cardiac death (SCD) remains a major clinical challenge. Abnormal ventricular repolarization is associated with increased risk of lethal ventricular arrhythmias and SCD. Hypothesis: We investigated the hypothesis that spatial repolarization heterogeneity can identify patients at risk for SCD in general population. Methods: Spatial R-, J- and T-wave heterogeneities (RWH, JWH and TWH, respectively) were automatically analyzed with second central moment technique from standard digital 12-lead ECGs in 5618 adults (46% men; age 50.9±12.5 yrs.) who took part in Health 2000 Study, an epidemiological survey representative of the entire Finnish adult population. During average follow-up of 7.7±1.4 years, a total of 72 SCDs occurred. Thresholds of RWH, JWH and TWH were based on optimal cutoff points from ROC curves. Results: Increased RWH, JWH and TWH (Fig.1) in left precordial leads (V4-V6) were univariately associated with SCD (P<0.001, each). When adjusted with clinical risk markers (age, gender, BMI, systolic blood pressure, cholesterol, heart rate, left ventricular hypertrophy, QRS duration, arterial hypertension, diabetes, coronary heart disease and previous myocardial infarction) JWH and TWH remained as independent predictors of SCD. Increased TWH (≥102μV) was associated with a 1.9-fold adjusted relative risk (95% confidence interval [CI]: 1.2 - 3.1; P=0.011) and increased JWH (≥123μV) with a 2.0-fold adjusted relative risk for SCD (95% CI: 1.2 - 3.3; P=0.004). When both TWH and JWH were above threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI: 1.7 - 6.2; P<0.001). When all heterogeneity measures (RWH, JWH and TWH) were above threshold, the risk for SCD was 3.7-fold (95% CI: 1.6 - 8.6; P=0.003). Conclusions: Automated measurement of spatial J- and T-wave heterogeneity enables analysis of high patient volumes and is able to stratify SCD risk in general population.

scholarly journals CYP2C19 genotype-guided antiplatelet therapy: promises and pitfalls

2020 ◽  
Vol 21 (12) ◽  
pp. 889-897
Author(s):  
Moataz Ellithi ◽  
Jordan Baye ◽  
Russell A Wilke
Keyword(s):  
Cytochromes P450 ◽  
Coronary Intervention ◽  
Antiplatelet Drug ◽  
Major Adverse Cardiovascular Events ◽  
Gene Variants ◽  
Loss Of Function ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Genes Encoding ◽  
Cyp2c19 Gene

Pharmacogenetic variants can alter the mechanism of action (pharmacodynamic gene variants) or kinetic processes such as absorption, distribution, metabolism and elimination (pharmacokinetic gene variants). Many initial successes in precision medicine occurred in the context of genes encoding the cytochromes P450 (CYP enzymes). CYP2C19 activates the antiplatelet drug clopidogrel, and polymorphisms in the CYP2C19 gene are known to alter the outcome for patients taking clopidogrel in the context of cardiovascular disease. CYP2C19 loss-of-function alleles are specifically associated with increased risk for coronary stent thrombosis and major adverse cardiovascular events in patients taking clopidogrel following percutaneous coronary intervention. We explore successes and challenges encountered as the clinical and scientific communities advance CYP2C19 genotyping in the context of routine patient care.

Effect of oral antiplatelet agents on major bleeding in users of coumarins

2008 ◽  
Vol 100 (12) ◽  
pp. 1076-1083 ◽  
Author(s):  
Olaf H. Klungel ◽  
Patrick C. Souverein ◽  
Anthonius de Boer ◽  
Tom Schalekamp
Keyword(s):  
Major Bleeding ◽  
Conditional Logistic Regression ◽  
Vitamin K Antagonists ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Primary Diagnosis ◽  
Antiplatelet Drugs ◽  
Antiplatelet Drug ◽  
Concurrent Use ◽  
Increased Risk

SummaryTreatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data froma Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI).We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2–6.9 and OR 1.6, 95% CI 1.3–1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0–2.3 and OR 1.8, 95 % CI 1.0–3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

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