Pierre Deharo

Impact of Obesity and the Metabolic Syndrome on Response to Clopidogrel or Prasugrel and Bleeding Risk in Patients Treated After Coronary Stenting

This study aimed to analyze the impact of body mass index (BMI) and the metabolic syndrome (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRI VASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p = 0.03. This impaired response was only observed in obese patients with the MS, and obese with the MS had significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI.

Timing of Angiography and Outcomes in High-Risk Patients with Non-ST Segment Elevation Myocardial Infarction Managed Invasively: Insights from the TAO Trial.

Background: In patients with non–ST-segment–elevation myocardial infarction (NSTEMI) and GRACE (Global Registry of Acute Coronary Events) score >140, coronary angiography (CAG) is recommended by European and American guidelines within 24 hours. We sought to study the association of very early (ie, ⩽12 hours), early (12–24 hours), and delayed (>24 hours) CAG in patients with NSTEMI with GRACE score >140 with ischemic outcomes. Methods: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with NSTEMI and CAG scheduled within 72 hours to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, patients with a GRACE score >140 were categorized into 3 groups according to timing of CAG from admission (<12, ≥12–<24, and ≥24 hours). The primary ischemic outcome was the composite of all-cause death and myocardial infarction within 180 days of randomization. Results: CAG was performed in 4071 patients (<12 hours, n=1648 [40.5%]; 12–24 hours, n=1420 [34.9%]; ≥24 hours, n=1003 [24.6%]). With CAG ≥24 hours as a reference, CAG from 12 to 24 hours was not associated with a lower risk of primary ischemic outcome at 180 days (odds ratio, 0.96; 95% confidence interval, 0.75–1.23), whereas CAG <12 hours was associated with a lower risk of death and myocardial infarction (odds ratio, 0.71; 95% confidence interval, 0.55–0.91). Performing CAG <12 hours was also associated with a lower risk of death and myocardial infarction (odds ratio, 0.76; 95% confidence interval, 0.61–0.94; P=0.01) compared with CAG performed at 12 to 24 hours. No difference was observed in bleeding complications. Conclusions: In patients with high-risk NSTEMI, undergoing CAG within the initial 12 hours after admission (as opposed to later, either 12–24 or ≥24 hours) was associated with lower risk of ischemic outcomes at 180 days.

Timing of Angiography and Outcomes in High-Risk Patients With Non–ST-Segment–Elevation Myocardial Infarction Managed Invasively: Insights From the TAO Trial (Treatment of Acute Coronary Syndrome With Otamixaban)

Background: In patients with non–ST-segment–elevation myocardial infarction (NSTEMI) and GRACE (Global Registry of Acute Coronary Events) score >140, coronary angiography (CAG) is recommended by European and American guidelines within 24 hours. We sought to study the association of very early (ie, ⩽12 hours), early (12–24 hours), and delayed (>24 hours) CAG in patients with NSTEMI with GRACE score >140 with ischemic outcomes. Methods: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with NSTEMI and CAG scheduled within 72 hours to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, patients with a GRACE score >140 were categorized into 3 groups according to timing of CAG from admission (<12, ≥12–<24, and ≥24 hours). The primary ischemic outcome was the composite of all-cause death and myocardial infarction within 180 days of randomization. Results: CAG was performed in 4071 patients (<12 hours, n=1648 [40.5%]; 12–24 hours, n=1420 [34.9%]; ≥24 hours, n=1003 [24.6%]). With CAG ≥24 hours as a reference, CAG from 12 to 24 hours was not associated with a lower risk of primary ischemic outcome at 180 days (odds ratio, 0.96; 95% confidence interval, 0.75–1.23), whereas CAG <12 hours was associated with a lower risk of death and myocardial infarction (odds ratio, 0.71; 95% confidence interval, 0.55–0.91). Performing CAG <12 hours was also associated with a lower risk of death and myocardial infarction (odds ratio, 0.76; 95% confidence interval, 0.61–0.94; P=0.01) compared with CAG performed at 12 to 24 hours. No difference was observed in bleeding complications. Conclusions: In patients with high-risk NSTEMI, undergoing CAG within the initial 12 hours after admission (as opposed to later, either 12–24 or ≥24 hours) was associated with lower risk of ischemic outcomes at 180 days.

Reply: De-Escalation of the P2Y12 Inhibitor After Acute Coronary Syndromes According to On-Treatment Platelet Reactivity: A Promising Step of Enormous Magnitude That Should Be Explored

We have read with great interest the letter from Dr. Lozano and colleagues about our paper assessing the impact of on-treatment platelet reactivity on switching strategy after acute coronary syndrome (ACS) [(1)][1]. First, we would like to thank the authors for their comments and the interest

Benefit of switching dual antiplatelet therapy after ACS on dual antiplatelet therapy adherence: A prespecified analysis of the TOPIC randomized study

Background The Timing Of Platelet Inhibition after acute Coronary Syndrome (TOPIC) trial showed that switching dual antiplatelet (DAPT) from aspirin plus a newer P2Y12 blocker (prasugrel or ticagrelor) to aspirin plus clopidogrel 1xa0month after an acute coronary syndrome (ACS) led to a reduction in bleeding complications with similar risk of ischemic recurrence. Purpose The objective of this prespecified analysis was to evaluate the impact of switching strategy on DAPT adherence. Methods TOPIC study randomized patients admitted for an ACS without adverse event at 1 month on aspirin and a newer P2Y12 blocker, to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). Medical adherence to prescribed DAPT was assessed at 6 months and 1 year. Results Six hundred and forty-six patients were randomized and 645 analyzed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. At 6 months and 1 year, the allocated DAPT regimen was significantly used more often in the switched group than in the unchanged DAPT group: 298 (92.5%) vs. 264 (81.7%) (Pxa0 Fig. 1 ). In multivariable analysis, unchanged DAPT strategy and ischemic or bleeding events were significantly associated with non-adherence to prescribed DAPT ( Table 1 ). Conclusion A switched DAPT was associated with significant improvement in the number of patients on prescribed DAPT at 6 months and 1 year following ACS. This improved adherence was related to reduction of side effects.

0010: Impact of thienopyridines on platelet CD40L biodisponibility after an acute coronary syndrome in relation with bleeding events

Background CD40 Ligand (CD40L) is expressed on platelets upon ADP stimulation and is involved in haemostasis. CD40L deficient mice exhibit thrombus instability and increased bleeding time. Methods We investigated the relationships between plasma and platelet-associated CD40L, ADP signaling and bleeding event occurrence in patients receiving thienopyridines one month after a stented Acute Coronary Syndrome (ACS). Basal platelet CD40L surface expression (pCD40L), pCD40L after PAR-1 agonist stimulation (TRAP pCD40L) and platelet released CD40L (rCD40L) were quantified. Results were compared to VASP as a measure of P2Y12 inhibition level. Results We included 318 patients between November 2012 and June 2014. Thienopyridines treated patients exhibit low pCD40L, TRAP pCD40L and rCD40L in comparison with controls. pCD40L and rCD40L were correlated with PRI-VASP. Thienopyridine treatment strongly reduces rCD40L. Hyperesponder to thienopyridine status is associated with high levels of TRAP pCD40L. pCD40L and TRAP pCD40L levels are reduced in the bleeding cohort. In multivariate analysis pCD40L significantly contributes to bleeding risk independently of PRI-VASP. Conclusion pCD40L and rCD40L levels are reduced by thienopyridines. pCD40L associates with the bleeding risk independently of the VASP levels and may represent a novel target to assess bleeding risk in thienopyridine-treated ACS patients.

0230: Effectiveness of switching Prasugrel's ‘low responders’ to ticagrelor after acute coronary syndrome

Aims This study aimed to assess the effectiveness and safety of switching from Prasugrel to Ticagrelor patients identified as Prasugrel low-responders one month after ACS. Methods and results 540 patients admitted for ACS with coronary stent implantation and discharged on Prasugrel 10mg were screened. Prasugrel response was assessed one month after discharge using Platelet Reactivity Index Vasodilatator Stimulated Phosphoprotein (PRI VASP). High on-Treatment Platelet Reactivity (HTPR) was defined as VASP>50%. Patients with HTPR were enrolled and switched to Ticagrelor 90 mg twice a day. They were re-tested a month later. Primary endpoint was defined as: comparison of degree of platelet inhibition and incidence of HTPR one month after switching to Ticagrelor in patients with HTPR on Prasugrel therapy. The safety endpoint was the incidence of bleedings under Ticagrelor as compared with Prasugrel therapy, using the Bleeding Academic Research Consensus definition. Between March 2010 and November 2013, 19 patients were defined as HTPR on Prasugrel 10 mg one month after ACS, with a mean VASP of 59,3%. Among these patients, 14 were switched to Ticagrelor 180 mg daily and, at one month, we observed a significant decrease in PRI VASP, with a mean value at 19.6% (p Conclusion Switch to Ticagrelor in Prasugrels “low responders” patients is an effective strategy, leading to an adequate platelet inhibition in a large majority of patients. This biological tailored approach could be useful in preventing ischemic complications, in this specific high risk population, potentially increasing bleeding risk. This hypothesis needs to be confirmed in large clinical studies. Download : Download full-size image Abstract 0230 – Figure