Influence of Amlodipine on Haemostatic Measurements during Clopidogrel Treatment in Patients with Coronary Artery Disease

2019 ◽  
Vol 119 (02) ◽  
pp. 264-273 ◽  
Author(s):  
Jin-Sin Koh ◽  
Yongwhi Park ◽  
Jong-Hwa Ahn ◽  
Min Gyu Kang ◽  
Kye-Hwan Kim ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Fibrin Clot ◽  
Open Label ◽  
Clot Strength ◽  
Asian Patients ◽  
Verifynow Assay ◽  
Risk Patients ◽  
Artery Disease

AbstractAmlodipine has a potential to reduce clopidogrel bioactivation through the cytochrome P450 3A4 enzyme in vivo, but the clinical impact of this interaction remains controversial. This randomized, open-label, two-period, crossover study was performed to evaluate the influence of amlodipine on the haemostatic profiles of high-risk patients during clopidogrel treatment. We recruited 40 Asian patients (Male/Female: n = 36/4) receiving clopidogrel (75 mg/day), aspirin (100 mg/day) and rosuvastatin for at least 6 months following percutaneous coronary intervention. Patients were randomly assigned to receive either 5 mg daily amlodipine or not for 2 weeks, and then were crossed over to the other treatment for 2 weeks. Haemostatic measurements were conducted with the VerifyNow assay and thromboelastography (TEG). Primary endpoint was P2Y12 Reaction Units (PRU) during on- versus off-amlodipine treatment. The on-amlodipine strategy showed higher level of PRU compared with the off-amlodipine strategy (176.8 ± 75.4 vs. 150.7 ± 65.5 PRU; ∆mean: 26.1 PRU; ∆95% confidence interval [CI]: 4.5–47.7 PRU; p = 0.019). Platelet-fibrin clot strength measured by TEG was lower during on- versus off-amlodipine treatment (7,712 ± 1,889 vs. 8,559 ± 2,174 dyne/cm2; ∆mean: –847 dyne/cm2; ∆95% CI: –1,632 to –62 dyne/cm2; p = 0.035). After amlodipine discontinuation, 27 patients (67.5%) showed a decrease in PRU, which was associated with ‘PRU ≥ 160 on-amlodipine’ in multivariate analysis (odds ratio: 62.014; 95% CI: 2.302–1670.328; p = 0.014). In conclusion, amlodipine increases platelet reactivity and decreases platelet-fibrin clot strength during clopidogrel treatment. In addition, the effect of amlodipine discontinuation on clopidogrel responsiveness is associated with on-amlodipine platelet reactivity.

Abstract 17577: Searching for the Optimal Regimen of Potent P2Y12 Inhibitor in East Asian Patients with Acute Coronary Syndrome: A Pharmacodynamic Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jang-Young Kim ◽  
Ji Hyun Lee ◽  
Jun-Won Lee ◽  
Young Jin Youn ◽  
Min-Soo Ahn ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Platelet Reactivity ◽  
East Asian ◽  
Coronary Intervention ◽  
Therapeutic Window ◽  
Coronary Syndrome ◽  
Asian Patients ◽  
Verifynow Assay ◽  
Optimal Maintenance ◽  
East Asian Patients

Introduction: The efficacy of prasugrel and ticagrelor has not been well evaluated in East Asian. We sought to compare the pharmacodynamic efficacy of prasugrel and ticagrelor by using VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). Methods: From 2012 January to 2014 April, we selected 83 patients who were administered ticagrelor 90 mg twice daily (n = 24), prasugrel 10 mg daily (n = 39), or prasugrel 5 mg daily (n = 20) after percutaneous coronary intervention due to acute coronary syndrome in our institute. After 3-4 weeks, on-treatment platelet reactivity (OPR) was measured by VerifyNow assay. According to the previous studies, we used 2 different criteria for the therapeutic window of OPR (East Asian criteria: 275≥PRU>85; Western criteria: 208 ≥PRU>85). We compared the OPR and the proportion of the therapeutic window between 3 groups. Results: The OPR was the lowest in the ticagrelor group, followed by the prasugrel 10 mg and prasugrel 5 mg groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, p < 0.001).When we used the East Asian criteria, the prasugrel 5 mg group had the highest proportion of patients in the therapeutic window of OPR followed by prasugrel 10mg and ticagrelor groups ( 90.0% vs. 46.2% vs. 12.5%, p < 0.001). When using Western criteria, the prasugrel 5mg group still showed the highest proportion of patients with therapeutic window followed by prasugrel 10mg and ticagrelor groups (60.0% vs. 43.6% vs. 12.5%, p<0.001). Conclusion: Short-term administration of prasugrel 5mg highly led the patients into the therapeutic window of OPR (in both of East Asian and Western criteria), compared with prasugrel 10mg and ticagrelor 180mg group. The prasugrel 5mg daily might be the optimal maintenance regimen for East Asian patients.

Thrombin-induced platelet-fibrin clot strength: Relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes

2014 ◽  
Vol 111 (04) ◽  
pp. 713-724 ◽  
Author(s):  
Young-Hoon Jeong ◽  
Kevin Bliden ◽  
Alan Shuldiner ◽  
Udaya Tantry ◽  
Paul Gurbel
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Confidence Interval ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Fibrin Clot ◽  
Hazard Ratio ◽  
Clot Strength ◽  
Increased Risk ◽  
Percutaneous Coronary

SummaryThe relationship between thrombin-induced platelet-fibrin clot strength (MATHROMBIN), genotype and high on-treatment platelet reactivity (HPR) is unknown. The aim of this study is to assess the influence of MATHROMBIN measured by thrombelastography on HPR and long-term major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients during aspirin and clopidogrel therapy. MATHROMBIN, platelet aggregation, genotype, and two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 µM ADP-induced PR46% measured by conventional aggregometry. Both high MATHROMBIN ( 68 mm) and CYP2C19*2 allele carriage were independently associated with ADP-induced platelet aggregation ([uni03B2] coefficient: 8.3% and 12.0%, respectively). The combination of CYP2C19*2 allele carriage and high MATHROMBIN increased the predictive value for the risk of HPR (odds ratio: 13.89; 95% confidence interval: 3.41 to 55.56; p < 0.001). MACE occurred in 25 patients (12.7%). HPR and high MATHROMBIN were both associated with MACE (hazard ratio: 3.09 and 2.24, respectively), and patients with both HPR and high MATHROMBIN showed an increased risk for MACE (adjusted hazard ratio: 5.56; 95% confidence interval: 1.85 to 16.67; p = 0.002). In conclusion, this is the first study to demonstrate that high platelet-fibrin clot strength is an independent determinant of HPR in PCI-treated patients. Combining the measurements of platelet aggregation and platelet-fibrin clot strength may enhance post-PCI risk stratification and deserves further study.

Management of the Asymptomatic Diabetic Patient with Evidence of Ischaemia

2010 ◽  
Vol 6 (1) ◽  
pp. 62
Author(s):  
Dimitrios Bliagos ◽  
Ajay J Kirtane ◽  
Jeffrey W Moses ◽  
◽  
◽  
...  
Keyword(s):  
Coronary Artery ◽  
Medical Therapy ◽  
Artery Bypass ◽  
Coronary Intervention ◽  
Diabetic Patients ◽  
Ageing Population ◽  
Patients With Diabetes ◽  
Risk Patients ◽  
Asymptomatic Diabetic Patient ◽  
Artery Disease

In the US, a total of 23.6 million people have diabetes, representing 7.8% of the population, and the prevalence of diabetes is on the rise due to an increasingly sedentary lifestyle, increasing obesity and an ageing population. Coronary artery disease is the leading cause of death in patients with diabetes, despite a reduction in cardiovascular events over the last 50 years, due in part to better medical therapy. Asymptomatic diabetic patients with evidence of ischaemia on stress testing have higher cardiac mortality; increasing amounts of ischaemia are associated with higher mortality rates. Revascularisation of high-risk patients, or those with significant ischaemia, has the potential to improve outcomes in this patient population. The choice of which revascularisation strategy to choose – either percutaneous coronary intervention (PCI) or coronary artery bypass grafting – should be carefully individualised, and must always be implemented against the background of optimal medical therapy.

scholarly journals Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial

2021 ◽  
Vol 10 (12) ◽  
pp. 2720
Author(s):  
Hyun-Woong Park ◽  
Min-Gyu Kang ◽  
Jong-Hwa Ahn ◽  
Jae-Seok Bae ◽  
Udaya S. Tantry ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Platelet Reactivity ◽  
Reactive Hyperemia ◽  
Open Label ◽  
Peripheral Arterial Tonometry ◽  
Coagulation Activity ◽  
Artery Disease

To evaluate the effect of clopidogrel vs. aspirin monotherapy on vascular function and hemostatic measurement. Background: Monotherapy with P2Y12 receptor inhibitor vs. aspirin can be a useful alterative to optimize clinical efficacy and safety in high-risk patients with coronary artery disease (CAD). Methods: We performed a randomized, open-label, two-period crossover study in stented patients receiving at least 6-month of dual antiplatelet therapy (DAPT). Thirty CAD patients with moderate-to-high ischemic risk were randomly assigned to receive either 75 mg of clopidogrel or 100 mg of aspirin daily for 4 weeks, and were crossed over to the other strategy for 4 weeks. Vascular function was evaluated with reactive hyperemia-peripheral arterial tonometry (RH-PAT) and brachial-ankle pulse wave velocity (baPWV). Hemostatic profiles were measured with VerifyNow and thromboelastography (TEG). The primary endpoint was the reactive hyperemia index (RHI) during clopidogrel or aspirin monotherapy. Results: Clopidogrel vs. aspirin monotherapy was associated with better endothelial function (RHI: 2.11 ± 0.77% vs. 1.87 ± 0.72%, p = 0.045), lower platelet reactivity (130 ± 64 vs. 214 ± 50 P2Y12 reaction unit [PRU], p < 0.001) and prolonged reaction time (TEG R: 5.5 ± 1.2 vs. 5.1 ± 1.1 min, p = 0.037). In multivariate analysis, normal endothelial function (RHI ≥ 2.1) was significantly associated with clot kinetics (TEG angle ≤ 68 degree) and ‘PRU ≤ 132’. ‘PRU ≤ 132’ was achieved in 46.2% vs. 3.8% during clopidogrel administration vs. aspirin monotherapy (odds ratio 21.4, 95% confidence interval 2.7 to 170.1, p < 0.001). Conclusions: In CAD patients, clopidogrel vs. aspirin monotherapy was associated with better endothelial function, greater platelet inhibition and lower coagulation activity, suggesting pleiotropic effects of clopidogrel on endothelial function and hemostatic profiles.

Platelet reactivity and clinical outcomes following percutaneous coronary intervention in complex higher-risk patients

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Michele M. Viscusi ◽  
Fabio Mangiacapra ◽  
Edoardo Bressi ◽  
Alessandro Sticchi ◽  
Iginio Colaiori ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Clinical Outcomes ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Percutaneous Coronary ◽  
Risk Patients

Drug-coated balloons for coronary artery disease: current concepts and controversies

2019 ◽  
Vol 15 (6) ◽  
pp. 437-454 ◽  
Author(s):  
Dario Buccheri ◽  
Renzo M Lombardo ◽  
Bernardo Cortese
Keyword(s):  
Bleeding Risk ◽  
Coronary Intervention ◽  
Side Branch ◽  
Bioresorbable Vascular Scaffold ◽  
Total Occlusion ◽  
Small Vessels ◽  
Stent Restenosis ◽  
Risk Patients ◽  
Artery Disease ◽  
High Bleeding Risk

Drug-coated balloons (DCBs) are a novel development for percutaneous coronary intervention. The first successful application was in-stent restenosis but in recent years, strong evidence has been released for its use in native small-vessels disease. Additional applications such as acute myocardial infarction, chronic total occlusion and bifurcation lesions are still under investigation. This article reviews the key studies evaluating the role of DCBs in several settings and reports on interesting cases where DCBs showed positive results for high-risk patients with neoplasm, as well as with high bleeding risk, planned surgery or renal injury. We also highlight a new biodegradable therapy for coronary bifurcation treatment, in which a bioresorbable vascular scaffold is implanted in the main branch, completed with a DCB angioplasty in the side branch when a treatment is deemed necessary.

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