Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance

Cardiology ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 104-113 ◽  
Author(s):  
Gerasimos Siasos ◽  
Evangelos Oikonomou ◽  
Manolis Vavuranakis ◽  
Eleni Kokkou ◽  
Konstantinos Mourouzis ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Cardiovascular Outcome ◽  
P2y12 Receptor ◽  
Loss Of Function ◽  
Total Study Population ◽  
End Point ◽  
Percutaneous Coronary ◽  
The Impact

Objectives: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. Methods: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. Results: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. Conclusions: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.

Efficacy of Change to New P2Y12 Receptor Antagonists in Patients High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention

2014 ◽  
Vol 21 (7) ◽  
pp. 619-625 ◽  
Author(s):  
Rogelio Robledo-Nolasco ◽  
A. Godínez-Montes de Oca ◽  
J. F. Zaballa-Contreras ◽  
J. A. Suárez-Cuenca ◽  
P. Mondragón-Terán ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
P2y12 Receptor ◽  
Receptor Antagonists ◽  
Percutaneous Coronary

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

2018 ◽  
Vol 118 (02) ◽  
pp. 362-368 ◽  
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.

Abstract 596: Platelet inhibition by Ticagrelor in African American versus Caucasian patients after Percutaneous Coronary Intervention

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Pavan K Katikaneni ◽  
Kalgi Modi
Keyword(s):  
Percutaneous Coronary Intervention ◽  
African American ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Total Study Population ◽  
Percutaneous Coronary ◽  
Significant Difference ◽  
Study Population ◽  
Caucasian Patients

PLATO study showed that in acute coronary syndromes, treatment with Ticagrelor as compared with Clopidogrel significantly reduced the rate of death, myocardial infarction or stroke. In subgroup analysis based on race, no significant difference in primary end point was noted. However, African Americans (AA) comprised only 1.1% of study population. AA have greater mortality from coronary artery disease (CAD) and more likely to have high on-treatment platelet reactivity. Aim of our study is to compare the extent of platelet inhibition achieved by Ticagrelor and Clopidogrel in AA versus Caucasian patients undergoing percutaneous coronary intervention (PCI). Methods: 72 patients undergoing PCI during September to November 2014 were included in this study. All received Aspirin 325mg loading dose (LD) followed by 81mg maintenance dose, along with either Ticagrelor 180 mg LD followed by 90 mg twice-daily MD or Clopidogrel 600 mg LD followed by 75 mg once-daily MD. Platelet reactivity (PRU) was measured using the VerifyNow P2Y12 function assay 12-24h following MD and the average values calculated for each group. Results: 40 African American (55%) and 32 Caucasian (45%) patients were included. Ticagrelor was used in 45 (62.5%) and Clopidogrel was used in 27 patients (37.5%). Among Caucasians, 16 (50%) received Ticagrelor and 16 (50%) received Clopidogrel. Among AA, 27 patients (67%) received Ticagrelor, 13 patients (33%) received Clopidogrel. In the total study population, the average PRU achieved was lower for Ticagrelor (44) compared with Clopidogrel (183). Among patients who received Ticagrelor, significantly lower average PRU was seen in AA (33) compared to Caucasians (63). Among patients who received Clopidogrel, similar average PRU was seen in AA (181) and Caucasian (185) groups. After combining Ticagrelor and Clopidogrel groups, lower average PRU was achieved in AA (76) compared to Caucasians (126), the difference primarily attributable to Ticagrelor. Conclusion: Ticagrelor achieved greater platelet inhibition in AAs compared to Caucasians, while Clopidogrel achieved similar platelet inhibition in both racial groups. This potentially greater platelet inhibition by Ticagrelor in high risk AA group merits investigation in large-scale studies.

P1934Platelet inhibitory profiles of prasugrel versus ticagrelor in patients with CYP2C19 loss-of-function genotypes undergoing percutaneous coronary intervention: results of a randomized feasibility study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Franchi ◽  
F Rollini ◽  
J Rivas ◽  
A Rivas ◽  
M Agarwal ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Clinical Practice ◽  
Genetic Testing ◽  
Primary Endpoint ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Loss Of Function ◽  
Time Points ◽  
Percutaneous Coronary ◽  
Rapid Genetic Testing

Abstract Background Although clopidogrel is the most widely used P2Y12 inhibitor, loss-of-function (LOF) allelic variants located within the hepatic cytochrome P450 (CYP) 2C19 gene lead to attenuated bioactivation, increased rates of high platelet reactivity (HPR), and worse outcomes in patients undergoing percutaneous coronary intervention (PCI). Drug regulating authorities have suggested using alternative P2Y12 inhibitors (i.e., prasugrel or ticagrelor) in these patients. However, tailoring antiplatelet therapy in clinical practice according to results of genetic testing has been limited due to lack of access to promptly available results. Moreover, there are no head-to-head pharmacodynamic (PD) comparisons of prasugrel vs ticagrelor among patients with CYP2C19 LOF alleles. Purpose The aim of this study was to evaluate the feasibility of using rapid genetic testing in clinical practice and to compare the PD effects of prasugrel vs ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles. Methods This was a prospective, randomized study conducted in patients with stable coronary artery disease and non-ST elevation acute coronary syndrome scheduled for left heart catheterization (LHC) with the intent to undergo PCI. Patients underwent rapid genetic testing using the Spartan RX assay, which defines CYP2C19 genetic status within 1 hour, allowing patients to be genotyped the same day of their LHC. Patients who were carriers of at least one LOF (*2 or *3) allele were randomized to receive either prasugrel [60mg loading dose (LD) - 10mg/day maintenance dose (MD)] or ticagrelor (180mg LD - 90mg b.i.d MD). Blood samples for PD analysis by VerifyNow were collected at 5 time points: baseline (prior to PCI), 30 minutes, 2 hours, 24 hours (or at hospital discharge whichever came first), and 1–4 weeks post-LD. All patients were treated with aspirin. The primary endpoint of our study was the non-inferiority in platelet reactivity, measured as PRU, at 24 hours of prasugrel vs ticagrelor in LOF allele carriers. Results A total of 781 consecutive patients scheduled for LHC were genotyped, of whom 223 (28.5%) were carriers of at least one LOF. Of these, 65 patients underwent PCI and randomized to prasugrel (n=32) vs ticagrelor (n=33). PRU levels at 24 hours were 33 vs 36 (prasugrel vs ticagrelor; mean difference = −3; 95% CI: −28 to 22; p=0.814) meeting the primary endpoint of non-inferiority. Both prasugrel and ticagrelor significantly reduced PRU to a similar extent with no differences between groups at all other time points (Figure). Accordingly, HPR rates were low and similar between groups. PRU by VerifyNow Conclusion Rapid genetic testing using the Spartan assay is feasible providing results in a timely fashion in a real-world clinical practice of patients undergoing PCI. Among patients with CYP2C19 LOF carrier status, prasugrel and ticagrelor are associated with similar levels of platelet inhibition. Acknowledgement/Funding Genetic testing was provided by Spartan RX

scholarly journals Using Pharmacogenetic Testing or Platelet Reactivity Testing to Tailor Antiplatelet Therapy: Are Asians different from Caucasians?

2018 ◽  
Vol 13 (2) ◽  
pp. 112 ◽  
Author(s):  
Doreen Tan Su-Yin ◽  
Keyword(s):  
Platelet Reactivity ◽  
Treatment Strategies ◽  
Coronary Intervention ◽  
Loss Of Function ◽  
Coronary Syndrome ◽  
Gene Testing ◽  
Percutaneous Coronary ◽  
High Prevalence ◽  
Different Populations ◽  
The Impact

All studies to date involving platelet reactivity and gene testing document singular interventions and their associations with outcomes. The East Asian paradox has been well documented – Asians who have had a percutaneous coronary intervention (PCI) are at a lower risk of ischaemic events even though they have a higher platelet reactivity. Asians who have had a PCI also have a higher risk of bleeding. This article covers the differences in outcomes between Caucasians and Asians, and explores the impact of outcomes, highlighting differences between the two patient populations. Given the high prevalence of loss-of-function alleles in Asia, treatment strategies will differ for different populations. It is plausible that both platelet reactivity and gene testing should be used to inform holistic decision-making for all patients – Caucasian or Asian – with acute coronary syndrome who are undergoing PCI.

Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

2012 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Donald E Cutlip ◽  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Statistical Significance ◽  
Bare Metal Stents ◽  
Coronary Intervention ◽  
Metal Stents ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Patients With Diabetes ◽  
The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

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