Impact of Intravenous P2Y12-Receptor Inhibition with Cangrelor in Patients Presenting with Acute Coronary Syndrome and Cardiogenic Shock – a Case Series

Background/Aims: Patients with acute coronary syndromes (ACS) presenting with cardiogenic shock (CS) are at particular risk for death and adverse cardiac events. Impaired effects and absorption of oral P2Y12-receptor inhibitors due to decreased organ hypoperfusion or hypothermia and challenges regarding oral administration contribute to this risk. We report a single center experience regarding the use of intravenous P2Y12-receptor inhibitor cangrelor in patients with CS treated with percutaneous coronary intervention (PCI). Methods: Twelve patients with ACS and CS undergoing PCI, not pretreated with oral P2Y12-receptor inhibitors, were treated with cangrelor. Platelet inhibition was assessed by multiple electrode aggregometry (MEA) before and after PCI, immediately and 2 hours after stopping the cangrelor infusion. Results: Nine patients recovered from their cardiogenic shock, 3 patients died. Platelet reactivity decreased from 65.9 (SD 41.0) U before PCI to 15.8 (SD 10.8) U after PCI, 13.4 (SD 7.7) U at the end of infusion and 33.8 (SD 19.9) 2 hours after stopping the cangrelor infusion. There was no non-responder under cangrelor infusion (MEA < 46 U). Conclusions: Due to its favorable PK/PD profile, cangrelor overcomes problems with reduced absorption and effects of oral P2Y12-receptor inhibitors and should be considered for periprocedural treatment of patients with CS.

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Potent P2Y12 receptor inhibitors in patients with acute coronary syndrome

Hämostaseologie ◽

10.5482/hamo-12-12-0022 ◽

2013 ◽

Vol 33 (01) ◽

pp. 9-15 ◽

Cited By ~ 6

Author(s):

M. Orban ◽

S. Massberg ◽

D. Sibbing

Keyword(s):

Acute Coronary Syndrome ◽

Large Scale ◽

Platelet Reactivity ◽

Blood Platelets ◽

Coronary Intervention ◽

Platelet Inhibition ◽

P2y12 Receptor ◽

Onset Of Action ◽

Thrombotic Risk ◽

Coronary Syndrome

SummaryBlood platelets are highly activated in the setting of an acute coronary syndrome (ACS). This fact mandates the need for potent platelet inhibition in ACS patients and especially in patients undergoing a percutaneous coronary intervention (PCI). The 2nd generation thienopyridine clopidogrel has been the standard of treatment in the past. Due to its pharmacological properties including a delayed onset of action, a large response variability and an insufficient antiplatelet action in some patients (low responsiveness or high on-treatment platelet reactivity), there was a need to develop, to study and to introduce more potent agents with a fast, reliable and potent antiplatelet action. With the 3rd generation thienopyridine prasugrel and with ticagrelor two potent agents for antiplatelet treatment of ACS patients are available now. Both drugs have demonstrated their superiority compared to clopidogrel in terms of thrombotic risk reduction in large-scale randomized trials. However, for these agents and in line with the expectations towards a more potent anti platelet treatment regimen, a higher risk for bleeding was observed for prasugrel and ticagrelor. Further on, the new anti platelet agents have their own and characteristic contraindications and numerous issues to be considered in clinical practice.This review aims to provide an overview on the state of the art P2Y12 receptor directed inhibition in ACS patients with a focus on patients undergoing a coronary stenting procedure.

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Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways

Thrombosis and Haemostasis ◽

10.1160/th13-03-0263 ◽

2013 ◽

Vol 110 (12) ◽

pp. 1223-1231 ◽

Cited By ~ 11

Author(s):

Dominick J. Angiolillo ◽

Jose L. Ferreiro ◽

Joseph A. Jakubowski ◽

Kenneth J. Winters ◽

Mark B. Effron ◽

...

Keyword(s):

Genetic Variants ◽

Active Metabolite ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Reactivity Index ◽

Coronary Syndrome ◽

Metabolite Generation ◽

Artery Disease ◽

The Impact

SummaryClopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

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Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1677549 ◽

2019 ◽

Vol 119 (04) ◽

pp. 660-667 ◽

Cited By ~ 1

Author(s):

Matthias Freynhofer ◽

Ralph Hein-Rothweiler ◽

Paul Haller ◽

Daniel Aradi ◽

Döme Dézsi ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Platelet Reactivity ◽

Adenosine Diphosphate ◽

Coronary Intervention ◽

Early Morning ◽

Platelet Inhibition ◽

Control Group ◽

Diurnal Variability ◽

Coronary Syndrome ◽

Adp Receptor

AbstractLong-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5–10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

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Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029616689300 ◽

2017 ◽

Vol 24 (3) ◽

pp. 452-461 ◽

Cited By ~ 1

Author(s):

Peng Ding ◽

Yujie Wei ◽

Nana Chen ◽

Huiliang Liu

Keyword(s):

Acute Coronary Syndrome ◽

Healthy Volunteers ◽

Chinese Population ◽

Platelet Reactivity ◽

Adenosine Diphosphate ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Reactivity Index ◽

Enzyme Linked Immunosorbent Assay ◽

Coronary Syndrome

The level of platelet reactivity during P2Y12-adenosine diphosphate receptor antagonist is associated with ischemic and bleeding risks following percutaneous coronary intervention in acute coronary syndrome. Determining platelet reactivity inhibition may be valuable for confirming effective platelet inhibition for individual patients and identifying patients at risk of bleeding. The enzyme-linked immunosorbent assay (ELISA)-based vasodilator-stimulated phosphoprotein (VASP) assay offers unique advantages over other methods and has not been used in the Chinese population. We enrolled 10 healthy volunteers and 54 patients with acute coronary syndrome. The volunteers received no treatment, and patients were administered a loading dose of clopidogrel or ticagrelor. The platelet reactivity index (PRI) was measured using flow cytometry (FC)-VASP and ELISA-VASP at baseline and 8-hour postloading dose. Blood samples of healthy volunteers and clopidogrel- or ticagrelor-treated patients were frozen and stored for 1, 2, and 4 weeks after initial activation. All frozen samples were tested using ELISA-VASP. The PRI assessed by FC-VASP and ELISA-VASP correlated well showing a high degree of consistency in identifying high or low on-treatment platelet reactivity. No significant time-dependent changes in PRI results were observed in frozen samples stored up to 4 weeks compared to nonfrozen samples. The PRI of ticagrelor-treated patients was lower than that of clopidogrel-treated patients. The ELISA-VASP effectively assesses the PRI, and results obtained from frozen specimens are unaffected by storage and shipment prior to assay. Ticagrelor was superior to clopidogrel in decreasing the PRI.

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Ticagrelor vs prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events

Thrombosis and Haemostasis ◽

10.1160/th14-02-0119 ◽

2014 ◽

Vol 112 (09) ◽

pp. 551-557 ◽

Cited By ~ 33

Author(s):

Katerina Stavrou ◽

Ioanna Koniari ◽

Vassilios Gkizas ◽

Angelos Perperis ◽

Kosmas Kontoprias ◽

...

Keyword(s):

Propensity Score ◽

Platelet Reactivity ◽

Academic Research ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Bleeding Events ◽

Clinical Trial Registration ◽

Propensity Score Model ◽

Coronary Syndrome

SummaryPlatelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58–0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3–37.3 vs 84.6, 95% CI 73.6–95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01774955.

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Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor

Thrombosis and Haemostasis ◽

10.1160/th17-07-0466 ◽

2018 ◽

Vol 118 (02) ◽

pp. 362-368 ◽

Cited By ~ 1

Author(s):

Christian Stratz ◽

Thomas Nührenberg ◽

Christian Valina ◽

Nikolaus Löffelhardt ◽

Kambis Mashayekhi ◽

...

Keyword(s):

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

P2y12 Receptor ◽

Elective Percutaneous Coronary Intervention ◽

Reticulated Platelets ◽

Impedance Aggregometry ◽

Percutaneous Coronary ◽

The Impact ◽

Receptor Inhibitor

Background Reticulated platelets are associated with impaired antiplatelet response to irreversibly acting P2Y12-receptor inhibitors. However, the impact of reticluated platelets (RP) on the reversibly acting injectable P2Y12-receptor inhibitor cangrelor is unknown. Thus, this study sought to investigate the influence of RP on cangrelor and transitioning strategies to oral P2Y12-receptor inhibitors. Methods This study randomized 110 patients undergoing elective percutaneous coronary intervention with use of cangrelor to different oral transitioning strategies loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor (n = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor (n = 20). ADP-induced platelet reactivity was assessed by impedance aggregometry. Reticulated platelets were analysed by an automated whole blood flow cytometry and described as immature platelet count. Results There was no correlation of reticulated platelets and ADP-induced platelet reactivity in patients under treatment with cangrelor (r = 0.06, p = 0.47). This finding was consistent in all three transitioning strategies. On day 1 following treatment with cangrelor, the correlation of reticulated platelets and platelet reactivity was detectable again in patients receiving thienopyridines but not ticagrelor (all patients r = 0.37, p < 0.001; clopidogrel: r = 0.59, p = 0.01; prasugrel: r = 0.47, p < 0.001; ticagrelor r = 0.22, p = 0.13). Conclusion Platelet inhibition is not influenced by levels of reticulated platelets during infusion of cangrelor independent of oral P2Y12-receptor inhibitor transitioning strategy. These findings underline the potency of cangrelor as immediate and reversibly acting P2Y12-receptor inhibitor.

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The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2018-0006 ◽

2018 ◽

Vol 33 (3) ◽

pp. 109-118 ◽

Cited By ~ 1

Author(s):

Karin B. Mirzaev ◽

Eric Rytkin ◽

Kristina A. Ryzhikova ◽

Elena A. Grishina ◽

Zhannet A. Sozaeva ◽

...

Keyword(s):

Logistic Regression ◽

Antiplatelet Therapy ◽

Early Phase ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

Categorical Variables ◽

P Value ◽

Coronary Syndrome ◽

Significant Difference

Abstract Background The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Methods Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Results Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19*2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, p<0.038) and PI (30.6±20.0 vs. 18.1±16.3, p<0.013) were observed, and the rates of high platelet reactivity (HPR) were lower in CYP2C19*1/*1 than those in CYP2C19*1/*2+CYP2C19*2/*2 (16.2% vs. 53.8% p<0.0067). In comparison, no significant difference in PRU value and PI was observed at <5 days between the rest of polymorphisms (p>0.05). Based on the logistic regression analysis, CYP2C19*2 (OR: 4.365, CI: 1.25–17.67, p=0.022) was an independent predictor of HPR at <5 days, as was the stent diameter (OR: 0.219, CI: 0.002–0.229, p=0.049). The remaining polymorphisms had no influence. Conclusions The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.

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Current Concepts in the Clinical Utility of Platelet Reactivity Testing

Interventional Cardiology Review ◽

10.15420/icr.2013.8.2.100 ◽

2013 ◽

Vol 8 (2) ◽

pp. 100 ◽

Cited By ~ 1

Author(s):

Collet Jean-Philippe ◽

Keyword(s):

Risk Factors ◽

Clinical Utility ◽

Platelet Reactivity ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Adenosine Diphosphate ◽

Coronary Intervention ◽

Therapeutic Window ◽

Cardiac Events ◽

Coronary Syndrome

The pharmacodynamic effect of clopidogrel varies among individuals; approximately a third will have high on-treatment platelet reactivity (HTPR) to adenosine diphosphate and may benefit from more intensive antiplatelet therapy. Platelet reactivity testing has an important role in monitoring the therapeutic efficiency of clopidogrel and the safety of more potent drugs that confer an increased bleeding risk, because it provides a direct measure of the biological effect of these drugs. Numerous studies have demonstrated an association between HTPR and the risk of cardiac events in acute coronary syndrome (ACS) or after percutaneous coronary intervention (PCI). While the prognostic value of platelet reactivity testing following PCI has been demonstrated repeatedly in cohort studies and meta-analyses, randomised controlled studies investigating the clinical utility of the technique to guide treatment decisions failed to improve clinical outcomes of clopidogrel-treated patients undergoing stent implantation. Available data suggest that platelet function monitoring may be carried out in clopidogrel-treated patients with a higher risk of thrombotic events. These include patient risk factors such as body mass index (BMI), type 2 diabetes, and those prior unexpected ischemic events such as stent thrombosis, as well as procedural risk factors. As we move towards conclusively defining a therapeutic window associated with both cardiovascular (upper threshold) and bleeding risk (lower threshold) for antiplatelet agents, platelet reactivity testing will become a central tool in the practice of personalised strategies.

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Impact of opioids on P2Y12 receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial

European Heart Journal - Cardiovascular Pharmacotherapy ◽

10.1093/ehjcvp/pvaa095 ◽

2020 ◽

Cited By ~ 2

Author(s):

Anne H Tavenier ◽

Renicus S Hermanides ◽

Jan Paul Ottervanger ◽

Rudolf Tolsma ◽

Antony van Beurden ◽

...

Keyword(s):

Myocardial Infarction ◽

Pain Relief ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

St Elevation Myocardial Infarction ◽

P2y12 Receptor ◽

Primary Pci ◽

Receptor Inhibition ◽

St Elevation

Abstract Aims Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI. Methods and results The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37–215) vs. 175 (63–228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32–509) vs. 60 ng/mL (13–206), P = 0.007], immediately after primary PCI [326 ng/mL (94–791) vs. 115 ng/mL (38–326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281–974) vs. 372 ng/mL (95–635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1–5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3–7); P = 0.96]. Conclusion The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

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A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome

Thrombosis and Haemostasis ◽

10.1160/th16-04-0340 ◽

2017 ◽

Vol 117 (02) ◽

pp. 303-310 ◽

Cited By ~ 18

Author(s):

Ali Pourdjabbar ◽

Benjamin Hibbert ◽

Aun-Yeong Chong ◽

Michel R. Le May ◽

Marino Labinaz ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Platelet Reactivity ◽

Bleeding Risk ◽

Platelet Inhibition ◽

Cardiac Events ◽

P2y12 Inhibitor ◽

Randomised Study ◽

Coronary Syndrome ◽

Adverse Cardiac Events ◽

Supplementary Material

SummaryTicagrelor has been endorsed by guidelines as the P2Y12 inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). Blood samples were collected at baseline, 12, 24, 48, 54, 60 and 72 hours (h) for assessment of platelet reactivity. The primary outcome was P2Y12 reactivity units (PRU) at 72 h. Secondary outcomes included: PRUs at each time point, incidence of high on-treatment platelet reactivity (HPR), major adverse cardiac events (MACE) and TIMI bleeding at 30 days. Serial PRUs increased after switching to clopidogrel in both groups. At 72 h, no difference in PRU was observed (165.8 ± 71.0 vs 184.1 ± 67.7, bolus vs no bolus, respectively, p=0.19). At 48 h the PRUs were significantly lower in the bolus arm (114 ± 73.1 vs 165.1 ± 70.5, respectively; p=0.0076) and at 72 h, there was a significant reduction in incidence of HPR (26.7 % vs 56.7 %, p=0.02). No differences in MACE or TIMI bleeding were observed. Although a bolus strategy was not associated with improved platelet inhibition at 72 h; at 48 h, platelet inhibition was superior with reduced incidence of HPR. Larger studies will be required to determine its clinical significance. Until then, decision for giving a bolus of clopidogrel at the time of a switch may in part be dependent on the indication for switching, especially if there are concerns for bleeding risk.Supplementary Material to this article is available online at www.thrombosis-online.com.

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