Generic Clopidogrel: Has Substitution for Brand Name Plavix® Been Effective?

2021 ◽  
pp. 089719002199700
Author(s):  
Erica S. Westphal ◽  
Traci Aladeen ◽  
Denis Vanini ◽  
Michelle Rainka ◽  
Kaitlin McCadden ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Significant Finding ◽  
Brand Name ◽  
Clopidogrel Bisulfate ◽  
Aggregation Response ◽  
Impedance Aggregometry ◽  
Resistance Rates ◽  
The Impact ◽  
Variability Data

Background: Following the expiration of brand name exclusivity of Plavix® in 2012, generic clopidogrel bisulfate was approved. As a widely prescribed medication with significant inter-patient pharmacokinetic and pharmacodynamic variability, data regarding the impact of switching to generic clopidogrel bisulfate on patients is needed. Objective: The objective of this study was to determine whether generic clopidogrel bisulfate is as efficacious as Plavix® for the inhibition of platelet aggregation. Methods: Patients treated with Plavix® monotherapy (n = 254) or generic clopidogrel bisulfate monotherapy (n = 185) were included in this retrospective review. Confounding factors previously found to affect clopidogrel responsiveness (diabetes, female sex, and smoking) were assessed, as well as medications classified as substrates, inducers, and inhibitors of enzymes involved in clopidogrel metabolism. Whole blood impedance aggregometry was used to measure platelet aggregation in response to adenosine diphosphate. Patients were tested after ≥2 weeks of treatment and designated as non-responders if aggregation response exceeded sensitivity thresholds of 6 ohms of impedance. Results: The introduction of generic clopidogrel bisulfate was associated with a decrease in antiplatelet resistance (44% to 31%, p < 0.01) and decreased mean ohms of resistance (5.06 ± 4.55 to 3.32 ± 4.03, p < 0.01). Prior to analysis of secondary outcomes, 217 patients were eliminated due to antiplatelet usage for longer than 3 years (n = 123 for Plavix® and n = 118 for clopidogrel). There was no statistically significant finding in prevalence of secondary events. Conclusion: Resistance rates to the antiplatelet, clopidogrel are significantly lower since the switch to generic formulations. Further investigation into the impact of variability between clopidogrel bisulfate formulations is needed.

scholarly journals Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1150
Author(s):  
Alberto Zanetto ◽  
Marco Senzolo ◽  
Elena Campello ◽  
Cristiana Bulato ◽  
Sabrina Gavasso ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Compensated Cirrhosis ◽  
Impedance Aggregometry ◽  
Child Class ◽  
Von Willebrand ◽  
Willebrand Factor

Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; p < 0.001), ASPI- (47 vs. 28; p < 0.001), and TRAP- (85 vs. 75; p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.

Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover

2016 ◽  
Vol 116 (11) ◽  
pp. 941-948 ◽  
Author(s):  
Thomas Nührenberg ◽  
Michael Amann ◽  
Marco Cederqvist ◽  
Pascal Kleiner ◽  
Christian M. Valina ◽  
...  
Keyword(s):  
Platelet Count ◽  
Drug Exposure ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Underlying Mechanism ◽  
Entire Cohort ◽  
Reticulated Platelets ◽  
Impedance Aggregometry ◽  
The Impact

SummaryReticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all timepoints (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals High Prevalence of Sticky Platelet Syndrome in Patients with Infertility and Pregnancy Loss

2019 ◽  
Vol 8 (9) ◽  
pp. 1328 ◽  
Author(s):  
Eray Yagmur ◽  
Eva Bast ◽  
Anja Susanne Mühlfeld ◽  
Alexander Koch ◽  
Ralf Weiskirchen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Pregnancy Loss ◽  
Low Dose ◽  
Light Transmission ◽  
Previous History ◽  
Adenosine Diphosphate ◽  
Healthy Controls ◽  
Live Births ◽  
Aggregation Response ◽  
History Of

Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients’ platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range −21 to 43%) compared to patients without SPS (median 59%, range 7–88% and p < 0.0001) and healthy controls (median 57%, range 8–106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.

Adenosine Diphosphate Breakdown by the Plasma of Different Species and by Human Whole Blood and White Cells

1967 ◽  
Vol 18 (03/04) ◽  
pp. 779-787 ◽  
Author(s):  
C. H Bolton ◽  
P. R Emmons
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Myocardial Infarctions ◽  
Breakdown Rate ◽  
Human Whole Blood ◽  
Platelet Poor Plasma ◽  
Aggregation Response

Summary1. The breakdown rate of ADP (200 µM/ml) by the platelet-poor plasma of the animals studied (human, rabbit, cat, sheep and rat) is consistent within a species and characteristic of that species.2. The breakdown rate of ADP is related directly to the B. M. R. of that species.3. The platelet aggregation response to ADP is extremely variable even within a species, and bears little, if any, relationship to ADP breakdown.4. The breakdown of ADP added to whole blood has been studied both in normal subjects and in patients with myocardial infarctions. The breakdown patterns were found to be identical.5. The ADP-ase activity of whole blood was localised almost entirely in the white cells.

Whole blood platelet aggregation kinetics under cardiopulmonary bypass: A pilot study

2019 ◽  
Vol 43 (3) ◽  
pp. 208-214
Author(s):  
Tobias Petzold ◽  
Erik Bagaev ◽  
Helen Herzog ◽  
Frank Born ◽  
Dominik Hoechter ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Platelet Aggregation ◽  
Life Support ◽  
Platelet Reactivity ◽  
Extracorporeal Life Support ◽  
Adenosine Diphosphate ◽  
Thrombin Receptor ◽  
Electrode Impedance ◽  
Platelet Counts ◽  
Impedance Aggregometry

Assessing the platelets’ functional status during surgery on cardiopulmonary bypass is challenging. This study used multiple electrode impedance aggregometry (Multiplate®) to create a timeline of platelet aggregation changes as induced by cardiopulmonary bypass in antiplatelet-naive patients undergoing elective surgery for mitral valve regurgitation. We performed six consecutive measurements (T1: pre-operatively, T2: after heparinization, T3: 3 min after establishment of cardiopulmonary bypass, T4: immediately after administration of cardioplegia, T5: 5 min after administration of cardioplegia, and T6: 45 min after administration of cardioplegia). Platelet aggregation was determined after stimulation with 3.2-μg/mL collagen, 6.4-μM adenosine diphosphate, and 32-μM thrombin receptor activating peptide. Five patients were included (age: 64 ± 10 years, one female). We observed a decrease in hematocrit levels by −17.1% ± 3.7% (T1 vs T6) with a drop after establishment of cardiopulmonary bypass (T2 vs T3) and slightly decreasing platelet counts by −6.2% ± 7.7% (T1 vs T6). Immediately after establishment of cardiopulmonary bypass (T2 vs T3), we observed reduced platelet aggregation responses for stimulation with adenosine diphosphate (−19.7% ± 12.8%) and thrombin receptor activating peptide (−19.3% ± 6.3%). Interestingly, we found augmented platelet aggregation for all stimuli 45 min after administration of cardioplegia (T5 vs T6) with the strongest increase for collagen (+83.4% ± 42.8%; adenosine diphosphate: +39.0% ± 37.2%; thrombin receptor activating peptide: +34.5% ± 18.5%). Thus, after an initial drop due to hemodilution upon establishment of cardiopulmonary bypass, platelet reactivity increased over time which was not outweighed by decreasing platelet counts due to mechanical platelet destruction and absorption. These findings have implications for rational transfusion, peri-operative antiplatelet therapy, and for the management of patients on other extracorporeal support, such as extracorporeal life support or extracorporeal membrane oxygenation.

Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial

2019 ◽  
Vol 6 (6) ◽  
pp. 372-381 ◽  
Author(s):  
Martin Orban ◽  
Dietmar Trenk ◽  
Tobias Geisler ◽  
Johannes Rieber ◽  
Martin Hadamitzky ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Clinical Outcomes ◽  
Smoking Status ◽  
Adenosine Diphosphate ◽  
Antiplatelet Drug ◽  
Control Group ◽  
Antiplatelet Treatment ◽  
Coronary Syndrome ◽  
The Impact

Abstract Aims Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. Methods and results The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64–1.56, P &gt; 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50–0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45–1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20–40)] vs. non-smoker [median 24 U (16–25), P &lt; 0.0001] in the control group and in current smokers [median 42 U, IQR (27–68)] vs. non-smoker [median 37 U, IQR (25–55), P &lt; 0.001] in the monitoring group. Conclusion Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

256Heart transplant recipients with cardiac allograft vasculopathy have increased platelet aggregation before and after low-dose aspirin therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K P Bjerre ◽  
T S Clemmensen ◽  
K Berg ◽  
S H Poulsen ◽  
S Dalby ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Aspirin Therapy ◽  
Term Survival ◽  
Allograft Vasculopathy ◽  
Antiplatelet Effect ◽  
Impedance Aggregometry ◽  
Before And After ◽  
Induced Aggregation

Abstract Background Following heart transplantation (HTx), long-term survival is reduced mainly due to development of a specific form of coronary artery disease, coronary allograft vasculopathy (CAV). Using optical coherence tomography to visualize the coronary artery wall, we have recently shown that layered fibrotic plaques resembling organized clots are the dominant plaque component in CAV. Thus, thrombosis is suggested as a possible mechanism contributing to development and progression of CAV. Aspirin is widely used after HTx despite limited evidence and lack of specific guidelines. The antiplatelet effect of aspirin has not been thoroughly examined in HTx-patients. Purpose To investigate baseline platelet aggregation and the antiplatelet effect of aspirin in HTx-patients with and without CAV. Methods We included 68 HTx-patients (median 8.6 years from HTx). In 66 patients taking 75 mg aspirin for a minimum of 7 days, platelet aggregation was measured in whole blood using impedance aggregometry with the following agonists: Adenosine diphosphate (ADP) stimulating ADP-receptors and arachidonic acid (AA) for monitoring of aspirin treatment. Aspirin compliance was confirmed by measuring serum-thromboxane B2. Platelet aggregation prior to aspirin therapy was measured in 59 patients as it was not considered clinically safe to interrupt ongoing aspirin treatment for one week prior to blood sampling in 9 patients mainly due to previous coronary stenting. CAV burden was determined by coronary angiography and echocardiography based on international classification. Patients were divided into two groups; no CAV (n=37) and CAV (n=29). Results In HTx-patients not treated with aspirin, we found significantly increased ADP-induced platelet aggregation in patients with CAV vs. patients without CAV (904 (95% CI 813–995) vs. 786 (95% CI 728–843) AU*min, P=0.02). Baseline AA-induced aggregation was also higher in patients with CAV vs. patients without CAV, though non-significant (994 (95% CI 907–1081) vs. 905 (95% CI 839–972) AU*min, P=0.10). Even though aspirin reduced AA-induced platelet aggregation in both groups, patients with CAV had significantly increased AA-induced platelet aggregation compared with patients without CAV on aspirin treatment (380 (95% CI 295–465) vs. 286 (95% CI 239–334) AU*min, P=0.04) (Fig. 1). Conclusions HTx-patients with CAV have increased platelet aggregation before and after aspirin treatment compared with HTx-patients without CAV. Aspirin monotherapy may not provide sufficient platelet inhibition in HTx-patients with CAV. Acknowledgement/Funding Aarhus University (PhD-salary)

scholarly journals Antiaggregatory activity of new 1-ethylxanthine cyclohexylammonium salt in vitro

2013 ◽  
Vol 94 (5) ◽  
pp. 692-695
Author(s):  
F Kh Kamilov ◽  
G A Timirkhanova ◽  
A I Samorodova ◽  
A V Samorodov ◽  
F A Khaliullin ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Platelet Aggregation ◽  
Aggregate Size ◽  
Adenosine Diphosphate ◽  
Biochemical Effect ◽  
Platelet Aggregate ◽  
Antiaggregatory Activity ◽  
The Impact ◽  
Induced Aggregation

Aim. To study the biochemical effect on hemostasis of a new cyclohexilammonium salt of 2-[1-ethyl-3-methyl-7(dioxotiethanyl-3)xantinyl-8-thio]acetic acid in vitro. Methods. Thromboelastography was performed using the citrate blood samples of healthy male donors. Global hemostatic effect, fibrinogen and platelet function, fibrinolysis and clot strength, and stability were analyzed at thromboelastography. The impact of firstly synthesized xantine derivative and pentoxifylline on the functional activity of platelets in vitro was studied using a laser analyzer of platelet aggregation. Adenosine diphosphate, collagen, epinephrine and ristocetin induced clotting were registered. General clotting characteristics, maximal aggregation values, maximal aggregation speed, mean platelet aggregate size, activity of platelet-derived factor 3, level of platelet-derived factor 4 were measured. Release of platelet-derived factors 3 and 4 at platelet aggregation were assessed after adenosinediphosphate-induced aggregation and centrifugation. Results. Cyclohexylammonium salt of 2-[1-ethyl-3-methyl-7-(dioxotiethanyl-3)xantinyl-8-thio]acetic acid in vitro showed antiaggregatory activity that exceeds such of pentoxifylline. It has been revealed that the second platelet aggregation wave, that is induced by small dose of adenosinediphosphate, is absent in the presence of the new cyclohexylammonium salt, lag-period in collagen-induced platelet aggregation elongates, and availability and release of platelet-derived factors 3 and 4 decreases. Conclusion. The research findings show potentially high antiaggregatory activity of 2-[1-ethyl-3-methyl-7-(dioxotiethanyl-3)xantinyl-8-thio]acetic acid cyclohexylammonium salt as an inhibitor of platelet release reaction.

Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel

2009 ◽  
Vol 101 (04) ◽  
pp. 714-719 ◽  
Author(s):  
Tanja Morath ◽  
Julia Stegherr ◽  
Siegmund Braun ◽  
Wolfgang Vogt ◽  
Martin Hadamitzky ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Platelet Response ◽  
Cross Sectional ◽  
Entire Study ◽  
Platelet Aggregometry ◽  
The Impact

SummaryPatients receiving dual antiplatelet treatment with aspirin and clopidogrel are commonly treated with proton pump inhibitors (PPIs). Attenuating effects on platelet response to clopidogrel have been reported solely for the PPI omeprazole. PPIs differ in their metabolisation properties as well as their potential for drug-drug interactions. The aim of this study was to investigate the impact of different PPIs (pantoprazole, omeprazole, esomeprazole) on platelet response to clopidogrel in patients with previous coronary stent placement under chronic clopidogrel treatment. In a cross-sectional observational study, consecutive patients under clopidogrel maintenance treatment (n=1,000) scheduled for a control coronary angiography were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry (MEA). From the entire study population, 268 (26.8%) patients were under PPI treatment at the time point of platelet function testing (pantoprazole, n=162; omeprazole, n=64; esomeprazole, n=42). Platelet aggregation (median [interquar-tile range]) was significantly higher in patients with omeprazole treatment (295.5 [193.5–571.2] AU*min) compared to patients without PPI treatment (220.0 [143.8–388.8] AU*min; p=0.001). Platelet aggregation was similar in patients with pantoprazole (226.0 [150.0–401.5] AU*min) or esomeprazole (209.0 [134.8–384.8] AU*min) treatment compared to patients without PPI treatment (p=0.69 and p=0.88, respectively). Attenuating effects of concomitant PPI treatment on platelet response to clopidogrel were restricted to the use of omeprazole. No attenuating effects on platelet response to clopidogrel were observed for pantoprazole or esomeprazole. Specifically designed and randomized clinical studies are needed to define the impact of concomitant PPI treatment on adverse events after percutaneous coronary intervention.

scholarly journals Adenos ine diphosphate-induced platelet aggregation in patients with coronary artery disease and concomitant anxiety and depression

2009 ◽  
Vol 15 (2) ◽  
pp. 181-184
Author(s):  
S. Kozlova ◽  
A. V. Golubev ◽  
U. S. Krylova ◽  
I. Y. Efimova ◽  
E. V. Shlyakhto ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Platelet Aggregation ◽  
Response Time ◽  
Adenosine Diphosphate ◽  
Anxiety And Depression ◽  
Aggregation Response ◽  
Artery Disease

We studied the changes in adenosine diphosphate (ADP)-induced platelet aggregation in patients with coronary artery disease (CAD) and concomitant anxiety and depression. We found a significant reduction of platelet aggregation response (time of aggregation at ADP concentration 1,25 and 2,5 µM, maximum percentages of aggregation at ADP concentrarion 1,25 µM) in plasma of patients with CAD and concomitant anxiety and depression as compared with patients with CAD without anxiety and depression. Our results do not support hypothesis of an increased thrombosis in patients with CAD and anxiety and depression.

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