scholarly journals Clopidogrel Resistance in Lower Extremity Arterial Endovascular Interventions

2019 ◽  
Vol 24 (38) ◽  
pp. 4554-4557
Author(s):  
Kyle M. Markel ◽  
Efthymios D. Avgerinos
Keyword(s):  
Lower Extremity ◽  
Platelet Reactivity ◽  
Large Population ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Loss Of Function ◽  
Clopidogrel Resistance ◽  
Endovascular Interventions ◽  
Prospective Trials ◽  
One Year

Antiplatelet pharmacotherapy for endovascular interventions has been widely adopted, with clopidogrel being one of the most common agents prescribed. A fraction of patients is resistant to clopidogrel resulting in decreased platelet inhibition despite adequate use. This finding is often termed high on-treatment platelet reactivity (HPR) and may lead to decreased patency in lower extremity arterial endovascular interventions. Current literature on HPR with lower extremity arterial endovascular interventions is limited to only a few studies. Resistance to clopidogrel is largely a result of CYP2C19 enzyme loss of function alleles. Several tests are available to measure clopidogrel resistance but light transmittance aggregometry remains the gold standard, yet direct genetic testing may be more reliable. One-year patency rates following lower extremity arterial endovascular interventions in patients with clopidogrel resistance (HPR) range between 35%-83% whereas those with the proper response to clopidogrel range between 73%-100%. Patients with decreased CYP2C19 activity show a significant decrease in one-year patency of endovascular femoropopliteal interventions (35% vs. 73%; p=0.006). Among patients tested for platelet function after in-stent thrombosis, up to 53% are resistant to clopidogrel. Lack of robust data limits our ability to predict patency in lower extremity arterial interventions for patients with HPR, but there is little doubt that longer patency seems to favor non-HPR patients. Large population, prospective trials are needed to guide our practice.

scholarly journals 4423 Impact of Gender on High On-Treatment Platelet Reactivity (HPR) and Major Adverse Cardiovascular Events (MACEs) in Caribbean Hispanic patients using Clopidogrel

2020 ◽  
Vol 4 (s1) ◽  
pp. 109-110
Author(s):  
Hector Jose Nunez Medina ◽  
Jorge Duconge ◽  
Luis A. Velez ◽  
Laura I. Fernandez ◽  
Orlando Arce
Keyword(s):  
Logistic Regression ◽  
Puerto Rico ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Arterial Disease ◽  
Platelet Inhibition ◽  
Major Adverse Cardiovascular Events ◽  
And Gender ◽  
One Year ◽  
Peripheral Arterial

OBJECTIVES/GOALS: The use of P2Y12 receptor inhibitors like Clopidogrel is crucial in the prevention of thrombotic events in patients with coronary artery disease, peripheral arterial disease, and cerebrovascular disease. Variation in the level of platelet inhibition is present in many patients, and it is associated with the occurrence of major adverse cardiovascular events (MACEs). The term High-on treatment platelet reactivity (HTRP) is used to describe impaired antiplatelet inhibition while on Clopidogrel. Multiple factors have been associated with the presence of HTPR in patients with CAD and PAD, including CYP2C19 loss of function polymorphism, drug-drug interactions, and medical comorbidities. Gender differences are another factor that might influence the levels of platelet inhibition while on Clopidogrel and hence, HTPR. Differences by Gender exist in platelet biology, count, and activation. The evidence for the influence of Gender in HTPR is limited, but a possible association has been described. In this study, we described the association of Gender with HTPR and Major Adverse Cardiovascular Events (MACEs) occurrence. The data is from a sample of Hispano-Caribbean patients on Clopidogrel therapy alone or in combination with Aspirin that were retrospectively evaluated from an ongoing trial in Puerto Rico. The result of this study provided evidence of the influence that Gender has on antiplatelet therapy function and MACEs occurrence. METHODS/STUDY POPULATION: The population in the study consisted of Hispano-Caribbean patients using Clopidogrel alone or in combination with Aspirin for coronary artery disease, peripheral arterial disease, or cerebrovascular disease. The sample was obtained from multiple hospital institutions with cardiovascular services in Puerto Rico during the years 2016-2019. Patients were part of the ongoing trial, “Adopting a precision medicine paradigm in Puerto Rico: leveraging ancestral diversity to identify predictors of Clopidogrel response in Caribbean Hispanics.” The sample size consisted of 150 patients. Participants were recruited during routine medical care, pre-admission evaluation for elective cardiac procedures, or during hospitalization in the participating institutions. Platelet reactivity testing was performed with the system Verify Now® to determine PRU values, and High on-treatment platelet reactivity was defined as PRU ≥208. One year after recruitment, the patients were re-evaluated for the occurrence of MACEs. The association of the variables HTPR, occurrence of MACEs, and Gender were assessed using logistic regression in addition to the role of HTPR and Gender for predicting MACE occurrence. The analysis was done using the statistic software Intellectus ©. RESULTS/ANTICIPATED RESULTS: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 for females and 170.81 for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the Odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01. DISCUSSION/SIGNIFICANCE OF IMPACT: The sample consisted of 67 females and 83 males with and Mean age of 67.87 years and 61.11 years, respectively. The prevalence of HTPR in the sample was 32.67 % (n = 49) with 36% (n = 24) for females, and 30%(n = 25) for males. The mean PRU values were 179.54 (±70.42) for females and 170.81(±64.89) for males. The percentage of MACEs one year after recruitment was 29.33 % (n = 44) with 43% on females (n = 19), and 57% on males (n = 25). Logistic regression for Gender predicting HTPR was non-significant with a χ2(2) = 0.55, p = .758, and McFadden R2 = 0.00. Also, logistic regression for the effects of Gender and HTPR on the odds of MACEs occurrence was not significant based on a model with an alpha of 0.05, χ2(2) = 1.99, p = .370, and McFadden R2 = 0.01.

Platelet Inhibition by Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel In Patients with Acute Myocardial Infarction According to Cytochrome P450 2C19 Genotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3322-3322
Author(s):  
In-Suk Kim ◽  
Young-Hoon Jeong ◽  
Arum Kim ◽  
Gyeong-Won Lee
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Platelet Aggregation ◽  
Maintenance Dose ◽  
Conflicts Of Interest ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Cyp2c19 Genotype ◽  
Loss Of Function

Abstract Abstract 3322 Objectives The aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to CYP2C19 genotype. Background Although adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can overcome the loss-of-function effect of CYP2C19 variants. Methods We randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150-mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow, platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (Aggmax). High post-treatment platelet reactivity (HPPR) was defined as 5 μmol/l ADP-induced Aggmax > 50%. Results In non-carriers, the two groups did not differ with respect to changes in platelet measures, and could achieve fewer rates of HPPR at 30-day follow-up (< 5%). In carriers, changes in 5 and 20 μmol/l ADP-induced Aggmax were significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple vs. high-MD group. Fewer patients in the triple group met the criteria of HPPR at 30-day follow-up compared with the high-MD group (2.6% vs. 21.1%, p = 0.014). Conclusions Among AMI patients with CYP2C19 variants, adjunctive cilostazol enhances platelet inhibition and reduces the rate of HPPR, as compared with high-MD clopidogrel. (Adjunctive Cilostazol Versus High-MD ClopidogrEL in Patients With Acute Myocardial Infarction According to CYP2C19 genotype [ACCEL-AMI-CYP2C19]; NCT00915733). Disclosures: No relevant conflicts of interest to declare.

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 127-130 ◽  
Author(s):  
Annemarie Mohring ◽  
Kerstin Piayda ◽  
Lisa Dannenberg ◽  
Saif Zako ◽  
Theresa Schneider ◽  
...  
Keyword(s):  
Gold Standard ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Area Under The Curve ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Characteristic Analysis ◽  
Specific Test ◽  
Current Gold Standard ◽  
Light Transmittance Aggregometry

Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points.

Clopidogrel resistance is common in patients undergoing vascular and coronary interventions

Vascular ◽  
2022 ◽  
pp. 170853812110593
Author(s):  
Adam M Berenson ◽  
Thomas N Hawken ◽  
Daniel G Fort ◽  
Samuel R Money ◽  
Stephen R Ramee ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Thrombotic Event ◽  
Detectable Effect ◽  
Exact Test ◽  
Clopidogrel Resistance ◽  
Coronary Interventions ◽  
Endovascular Interventions ◽  
Initial Cohort ◽  
Coronary Procedure ◽  
Clopidogrel Therapy

Objectives “Clopidogrel resistance,” also defined as heightened platelet reactivity (HPR) while on clopidogrel therapy, may lead to a sub-optimal antiplatelet effect and a potential thrombotic event. There is limited literature addressing the prevalence of HPR in a large cohort of patients receiving either coronary or endovascular interventions. Methods In a large integrated healthcare system, patients with a P2Y12 reaction units (PRU) test were identified. HPR was defined as a PRU ≥ 200 during clopidogrel therapy. Vascular and coronary interventions were identified utilizing CPT codes, HPR prevalence was calculated, and Fischer’s exact test was used to determine significance. Results From an initial cohort of 2,405,957 patients (October 2014 to January 2020), we identified 3301 patients with PRU tests administered. Of these, 1789 tests had a PRU ≥ 200 (HPR overall prevalence, 54%). We then identified 1195 patients who underwent either an endovascular or coronary procedure and had a PRU measurement. This corresponded to 935 coronary and 260 endovascular interventions. In the coronary cohort, the HPR prevalence was 54% (503/935). In the vascular cohort, the HPR prevalence was 53% (137/260); there was no difference between cohorts in HPR prevalence ( p = 0.78). Conclusion “Clopidogrel resistance” or HPR was found to be present in nearly half of patients with cardiovascular disease undergoing intervention. Our data suggest HPR is more common in the cardiovascular patient population than previously appreciated. Evaluating patients for HPR is both inexpensive ($25) and rapid (< 10 min). Future randomized studies are warranted to determine whether HPR has a clinically detectable effect on revascularization outcomes.

scholarly journals The Dynamic Effect of Non-CYP3A4-Metabolized and CYP3A4-Metabolized Statins on Clopidogrel Resistance in Patients With Cerebral Infarction

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong Ting Shi ◽  
Yong Yuan Chen ◽  
Xiao Ying Li ◽  
Jian Hua Luo ◽  
Guang Hong Zhong ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Chinese Population ◽  
Platelet Reactivity ◽  
Dynamic Effect ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Clopidogrel Resistance ◽  
Baseline Visit ◽  
Genotype Frequencies ◽  
Independent Risk Factors

Objective: To explore the treatment effect of statins used together with clopidogrel on cerebral infarction (CI).Methods: One hundred and thirty non-clopidogrel resistant patients were divided into a dynamic clopidogrel resistant (DCR) group and a continuous Non clopidogrel resistance (NCR) group. Patients were randomly assigned to AC group (atorvastatin 40 mg/d + clopidogrel, 51 patients) and RC group (rosuvastatin 20 mg/d + clopidogrel, 47 patients). The patient’s platelet aggregation rate (PAR) was measured on visit 0 (baseline), visit 1 (1 week after clopidogrel alone treatment), and visits 2 to 4 (one, three, and 6 months after clopidogrel plus statins treatment). The platelet reactivity index (PRI) was assessed on visits 0, 2, and 4, and clopidogrel thiol metabolite (H4) levels was measured on visits 2 and 4. DNA sequencing was used to determine CYP3A4, CYP2C9, and CYP2C19 genotypes in all patients.Results: PAR, PRI, and H4 levels, DCR ratio, and the genotype frequencies of CYP2C9*3εC, CYP2C19*2εA, and CYP2C19*3εA of both groups were similar (p &gt; 0.05). CYP2C19εA *2 and *3 were independent risk factors for DCR (p &lt; 0.05).Conclusion: Clopidogrel combined with atorvastatin does not affect platelet inhibition and does not increase the incidence of DCR. The incidence of DCR in the Chinese population is high and is related to CYP2C19εA.

scholarly journals Szemléletváltozás az alsó végtagi érrekonstrukciók gyakorlatában a Szegedi Tudományegyetem Érsebészeti Osztályán

2021 ◽  
Vol 162 (24) ◽  
pp. 943-951
Author(s):  
Tibor Takács ◽  
Gábor Mihalovits ◽  
Rita Váradi ◽  
András Nagy ◽  
Endre Nagy ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Similar Efficacy ◽  
Vascular Lesions ◽  
Limb Ischaemia ◽  
Endovascular Interventions ◽  
Hospitalization Time ◽  
Significant Difference ◽  
One Year ◽  
The One ◽  
Surgical Group

Összefoglaló. Bevezetés: Az endovascularis intervenciókat kezdetben radiológusok alkalmazták, manapság, megfelelő képzést követően, jó eredménnyel végeznek ilyen beavatkozásokat érsebészek is. Ezt a világszerte uralkodóvá váló szemléletet kívántuk meghonosítani a Szegedi Tudományegyetemen, melynek bevezetése nélkül előrevetíthető az érsebészet működésének átalakulása az érrekonstrukciós beavatkozások csökkenésével. Célkitűzés: Egyetemünkön radiológus- és érsebész-munkacsoport végez perifériás érintervenciókat. Célunk a két intézet alsó végtagi endovascularis tevékenységének összehasonlítása volt. Módszer: Vizsgálatunkba a Szegedi Tudományegyetemen 2012. 01. 01. és 2019. 12. 31. között alsó végtagi endovascularis beavatkozásokon átesett betegeket válogattuk be. A betegeket a rizikófaktoraik, a kezelt anatómiai régiók, a hospitalizációs idő és a szövődmények tekintetében hasonlítottuk össze. Egyéves utánkövetés során vizsgáltuk a ’redo’ műtétek , az amputációk és a halálozások gyakoriságát. Eredmények: A beavatkozásokat 653 esetben radiológus, 573 esetben érsebész végezte. Az érműtőben infrainguinalis (63,2%), a radiológián suprainguinalis érintervenciók (68,6%) történtek nagyobb arányban. A percutan végzett beavatkozásokat vizsgálva a hospitalizációs időben (2,5 ± 4,4 nap vs. 2,4 ± 2,5 nap, p = 0,78), valamint a minimálisan invazív módon végzett beavatkozások utáni szövődmények gyakoriságában (30/653 – 4,6% és 11/257 – 4,3%, p = 0,837) nem volt különbség a két betegcsoport között. ’Redo’ műtétek (73/485 – 15,1% és 33/562 – 5,9%, p<0,001) és amputációk (31/485 – 6,4% és 12/562 – 2,1%, p<0,001) gyakrabban fordultak elő az érműtőben kezelt betegek körében, ebben a csoportban azonban a kritikus végtagischaemia előfordulása is gyakoribb volt (45,4% és 38,6%, p = 0,016). A mortalitásban nem volt szignifikáns különbség (5,8% és 3,9%, p = 0,16). Következtetés: A szoliter érelváltozások kezelését mindkét intézet hasonló hatásfokkal végezte. A több anatómiai régiót érintő betegség miatt érműtőben végzett beavatkozások utáni szövődmények előfordulása kissé magasabbnak bizonyult. Orv Hetil. 2021; 162(24): 943–951. Summary. Introduction: Endovascular interventions were initially performed by radiologists. Nowadays properly trained vascular surgeons also effectively perform these interventions. We wished to apply this widespread practice at our university because without this advancement the number of reconstructive surgeries was expected to decrease significantly. Objective: Both radiologists and vascular surgeons perform endovascular interventions at our university. We compared the outcomes of lower extremity endovascular interventions between the two institutes. Method: We included patients who underwent lower extremity endovascular interventions between 01. 01. 2012 and 31. 12. 2019. We compared the risk factors, treated anatomical regions, hospitalization time and complication rate. During the one-year follow-up, we examined the occurrence of redo surgeries, amputations and mortality. Results: 653 interventions were performed by radiologists and 573 by vascular surgeons. Vascular surgeons carried out more interventions in the infrainguinal region (63.2%), while radiologists in the suprainguinal region (68.6%). The hospitalization time after percutaneous interventions (2.5 ± 4.4 days vs. 2.4 ± 2.5 days, p = 0.78), and the rate of complications after minimally invasive interventions did not show significant difference (30/653 – 4.6% vs. 11/257 – 4.3%, p = 0.837). Redo surgeries (73/485 – 15.1% vs. 33/562 – 5.9%, p<0.001) and amputations (31/485 – 6.4% vs. 12/562 – 2.1%, p<0.001) occurred more frequently in the surgical group. However, the incidence of chronic limb ischaemia was also higher (45.4% vs. 38.6%, p = 0.016). There was no significant difference in the mortality (5.8% vs. 3.9%, p = 0.16). Conclusion: Both institutes had similar efficacy in performing peripheral interventions on solitary vascular lesions. Complications occurred more frequently in the surgical group, but the majority of these patients had extended atherosclerotic diseases. Orv Hetil. 2021; 162(24): 943–951.

Clopidogrel Resistance and Aspirin Resistance - a Cause of Coronary Artery Stent Thrombosis?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4070-4070 ◽  
Author(s):  
Robert Klamroth ◽  
Stefan Hoffmann ◽  
Dietrich Andresen ◽  
Helmut Landgraf
Keyword(s):  
Coronary Artery ◽  
Platelet Aggregation ◽  
Stent Thrombosis ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Light Transmittance ◽  
Clopidogrel Resistance ◽  
Coronary Artery Stent

Abstract Background: Occlusions of coronary artery stents are a seldom but often fatal complication after coronary artery intervention. With aggressive platelet inhibition therapy (combination of Aspirin (ASS) and clopidogrel) a reduction of stent thrombosis to less than 2% was achieved. The inhibition of platelet function has great interindividual variability and resistance against ASS and/or clopidogrel were previously described. Therefore we studied the relation between coronary artery stent thrombosis and insufficient inhibition of platelet function in patients after coronary artery intervention. Methods: Between 2000 and 2003 we examined 20 patients (pts) with coronary artery stent thrombosis within 4 weeks after coronary artery intervention. All patients received a clopidogrel loading dose of 300mg followed by 75mg/die and ASS 100mg/die. Platelet inhibition was studied by light transmittance aggregometry in platelet rich plasma (Aggregometer PAP 4, moelab inc.). Aggregation was recorded as the maximum percentage change in light transmittance from baseline using platelet poor plasma as a reference. We defined ASS resistance as platelet aggregation > 30% after induction with 0,5mg/ml arachidonic acid and clopidogrel resistance as platelet aggregation > 30% after induction with 20 μmol ADP. We compared these pts with 20 pts without stent thrombosis within 4 weeks after coronary artery intervention. Results: In the group with coronary artery stent thrombosis we found 13/20 patients with insufficient platelet inhibition. 2/20 pts in this group were resistent against both ASS and clopidogrel. In 2/20 pts we observed ASS resistance and in 9/20 pts clopidgrel resistance. In the group of patients without stent thrombosis we found only 1/20 pt with ASS resistance and 1/20 pt with clopidogrel resistance. Conclusions: Insufficient platelet inhibition could be one cause of early stent thrombosis after coronory artery intervention. Platelet function testing is able to detect insufficient platelet inhibition and early testing could be an instrument to prevent coronary artery stent thrombosis.

Platelet function profiles in the elderly: Results of a pharmacodynamic study in patients on clopidogrel therapy and effects of switching to prasugrel 5 mg in patients with high platelet reactivity

2011 ◽  
Vol 106 (12) ◽  
pp. 1149-1157 ◽  
Author(s):  
Claudia Tamburino ◽  
Davide Capodanno ◽  
Eligio Miccichè ◽  
Lucia D’Urso ◽  
Valeria Calvi ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
The Elderly ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Considerable Proportion ◽  
Old Patients ◽  
High Platelet Reactivity ◽  
Clopidogrel Therapy

SummaryStudies specifically designed to assess clopidogrel response in the elderly as well as treatment alternatives to improve platelet inhibition in this highrisk population are lacking. This study aimed to define phar-macodynamic (PD) profiles, including high platelet reactivity (HPR) rates, among elderly patients on maintenance clopidogrel therapy and to assess the PD effects of prasugrel 5 mg/day in elderly with HPR. This was a prospective observational PD study enrolling consecutive ≥75-year-old patients on maintenance clopidogrel therapy (75 mg/day) who were tested for clopidogrel response by the VerifyNow P2Y12 assay and light transmittance aggregometry (LTA). HPR rates were estimated using multiple definitions. HPR patients identified by the VerifyNow P2Y12 assay [P2Y12 reaction unit (PRU) ≥230] were switched to prasugrel 5 mg/day, and platelet function testing was performed after 15 days of treatment. PD testing was completed in 100 patients. The HPR prevalence varied between 25% and 32%, depending on the definition used. A PRU ≥230 was observed in 25 patients; of these, 20 switched to prasugrel 5 mg/day. This resulted in significant reduction in PRU mean values (279.8 ± 45.1 vs. 171.7 ± 65.2, p=0.0002) with an absolute between-treatment difference of 108.1 (95% confidence intervals 75.2–140.9). Accordingly, switching to prasugrel 5 mg/day overcame HPR in most (80%) patients. Consistently, all LTA measures were significantly lower after prasugrel compared with clopidogrel. In conclusion, a considerable proportion of elderly patients exhibit HPR while on standard clopidogrel therapy. Switching to 5 mg/day prasugrel in elderly patients with HPR is associated with enhanced platelet inhibition and overcomes HPR in the majority of these patients.

2349Selatogrel, a novel P2Y12 inhibitor for emergency use, achieves rapid, consistent and sustained platelet inhibition following single-dose subcutaneous administration in stable CAD patients

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R F Storey ◽  
P A Gurbel ◽  
S James ◽  
J M Ten Berg ◽  
J.-F Tanguay ◽  
...  
Keyword(s):  
Single Dose ◽  
Platelet Reactivity ◽  
Venous Blood ◽  
Subcutaneous Administration ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Pharmacokinetic Data ◽  
Post Dose ◽  
P2y12 Inhibitor ◽  
Stable Cad

Abstract Background In the setting of AMI, rapid platelet inhibition is desirable but the onset of pharmacodynamic (PD) effect of oral platelet P2Y12 inhibitors is delayed, sometimes for hours. Subcutaneous (s.c) administration of a rapidly-acting P2Y12 inhibitor would overcome many of the limitations of available therapies. Patients with stable CAD were investigated initially. Purpose To characterise the inhibition of platelet aggregation and pharmacokinetics (PK) of a single dose of selatogrel, a novel s.c P2Y12 inhibitor, in patients with stable CAD. Methods Patients with stable CAD receiving oral antiplatelet therapy (aspirin and/or oral P2Y12 inhibitor) were randomized to 1 of 8 groups based on treatment (selatogrel or matching placebo), dose (8 mg or 16 mg) and s.c injection site (thigh or abdomen). Venous blood samples were collected into PPACK anticoagulant tubes. Platelet reactivity was assessed by VerifyNow PRU (P2Y12 reaction units) test before and 15 min, 30 min and 1, 2, 4, 8 and 24 h after injection. Light-transmittance aggregometry (LTA; ADP 20 uM) was also performed. PK samples were collected up to 24 h post-dose. Adverse events occurring within 30 days were recorded. Responders were defined as having PRU <100 at 30 min after injection and lasting ≥3 h. Results 345 patients (mean age 65 y; 20% female; 31% diabetes) received selatogrel 8 mg (n=114), selatogrel 16 mg (n=115) or placebo (n=116). 97% were on background therapy with aspirin (or its derivative carbasalate) and 35% with oral P2Y12 inhibitor (clopidogrel 23%, prasugrel 4%, ticagrelor 8%). 89% of subjects were responders to selatogrel 8 mg, 90% to selatogrel 16 mg and 16% to placebo (P<0.0001). At 15 min post-dose, PRU values (mean±SD) were 10±25 with selatogrel 8 mg, 5±10 with selatogrel 16 mg and 163±73 with placebo (Figure). PRU levels were maintained at 2 and 4 h for both doses and gradually returned to pre-dose levels by 24 h post-dose (Figure). LTA results were consistent with the VerifyNow results. PD responses were similar for thigh and abdomen injection sites. Selatogrel was well tolerated: mild dyspnoea (or moderate dyspnoea, n=1, with 16 mg) occurred in 5% and 9% with selatogrel 8 mg and 16 mg, respectively, vs 0% with placebo; dizziness occurred in 4% and 4% vs 1%, respectively, without significant haemodynamic or ECG changes. Bleeding events occurred in 9.6% and 4.3% with selatogrel 8 mg and 16 mg, respectively, vs 6.9% with placebo. Pharmacokinetic data will be presented. Conclusions Selatogrel has a rapid PD effect following s.c injection in patients with stable CAD, within 15 min in most patients. The consistent and high levels of P2Y12 inhibition with a single 8 mg or 16 mg dose are sustained for over 4 hours, following which platelet reactivity progressively recovers over 24 h. Selatogrel was well tolerated, with mostly mild, transient dyspnoea observed in <10% patients. These data support further studies of selatogrel for emergency treatment of AMI patients. Acknowledgement/Funding Fully funded by Idorsia Pharmaceuticals Ltd

Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions

2008 ◽  
Vol 99 (01) ◽  
pp. 161-168 ◽  
Author(s):  
Esther Bernardo ◽  
Jorge Palazuelos ◽  
Bhaloo Desai ◽  
Ian Weisberg ◽  
Fernando Alfonso ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Maintenance Dose ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Relative Increase ◽  
Light Transmittance ◽  
Functional Impact ◽  
Percutaneous Coronary

SummaryThe currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI).This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n=20) or 150 mg (n=20) daily maintenance dose of clopidogrel for 30 days;afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 μM and 5 μM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 μMADP-induced platelet aggregation compared to patients on 75 mg/day (52.1±9% vs. 64.0±8%; p<0.001; primary endpoint).The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p<0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 μM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI.

Sign in / Sign up

Export Citation Format

Share Document