Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation

2016 ◽  
Vol 115 (05) ◽  
pp. 960-968 ◽  
Author(s):  
Ulrike Flierl ◽  
Philipp Röntgen ◽  
Zauner Florian ◽  
Tongers Jörn ◽  
Berliner Dominik ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Therapeutic Hypothermia ◽  
Gastric Tube ◽  
Therapeutic Strategy ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Vasopressor Use ◽  
Hospital Cardiac Arrest

SummaryAcute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours(h) following a loading dose of 60 mg via a gastric tube. Mean PRI (±SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition.

Early determination of clopidogrel responsiveness by platelet reactivity index identifies patients at risk for cardiovascular events after myocardial infarction

2011 ◽  
Vol 106 (07) ◽  
pp. 141-148 ◽  
Author(s):  
Andreas Schäfer ◽  
Ulrike Flierl ◽  
Jürgen Kössler ◽  
Nora Seydelmann ◽  
Anna Kobsar ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Reactivity ◽  
Density Lipoprotein ◽  
Coronary Intervention ◽  
Platelet Inhibition ◽  
Systematic Evaluation ◽  
Reactivity Index ◽  
Operating Characteristics ◽  
Patients At Risk ◽  
Acute Mi

SummaryWhile acute myocardial infarction (MI) is associated with impaired clopidogrel responsiveness, systematic evaluation is lacking due to the inability of functional aggregation-based assays to analyse clopidogrel responsiveness in the presence of glycoprotein IIb/IIIa inhibitors. Using the P2Y12-specific, non-aggregation-based platelet-reactivity-index (PRI) we assessed clopidogrel responsiveness in patients with acute MI. Clopidogrel responsiveness was determined 24 hours (h) after loading with 600 mg clopidogrel in 54 patients with acute MI admitted for coronary intervention. A PRI > 50% was considered as suboptimal inhibition. Overall response in MI patients was suboptimal with a median PRI of 58%. Diabetes, low high-density lipoprotein and pre-hospital clopidogrel loading were associated with impaired clopidogrel responsiveness. Patients loaded at first medical contact had a significantly weaker platelet inhibition by clopidogrel after 24 h (PRI 63%) compared to those loaded peri-interventionally (PRI 54%, p=0.014). Clinical outcome was assessed as a combination of cardiac death, non-fatal MI, stent thrombosis, ischaemic stroke, and urgent target vessel revascularisation after 12 months. The pre-selected cut-off of PRI ≤ 50% yielded a sensitivity of 87% at a specificity of 26%, whereas a PRI ≤ 57% determined by receiver-operating characteristics (ROC)-analysis yielded a sensitivity of 80% at a specificity of 56% (event rate: PRI ≤ 57%: 12.0%; PRI > 57%: 41.4%, p=0.0136). In conclusion, PRI detects clopidogrel responsiveness in acute MI patients requiring glycoprotein IIb/IIIa antagonism; and impaired clopidogrel responsiveness predisposes to clinical events. Pre-hospital clopidogrel loading was associated with impaired response and more adverse events challenging the concept of earliest oral clopidogrel loading in MI patients.

Platelet Inhibition by Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel In Patients with Acute Myocardial Infarction According to Cytochrome P450 2C19 Genotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3322-3322
Author(s):  
In-Suk Kim ◽  
Young-Hoon Jeong ◽  
Arum Kim ◽  
Gyeong-Won Lee
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Platelet Aggregation ◽  
Maintenance Dose ◽  
Conflicts Of Interest ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Cyp2c19 Genotype ◽  
Loss Of Function

Abstract Abstract 3322 Objectives The aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to CYP2C19 genotype. Background Although adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can overcome the loss-of-function effect of CYP2C19 variants. Methods We randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150-mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow, platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (Aggmax). High post-treatment platelet reactivity (HPPR) was defined as 5 μmol/l ADP-induced Aggmax > 50%. Results In non-carriers, the two groups did not differ with respect to changes in platelet measures, and could achieve fewer rates of HPPR at 30-day follow-up (< 5%). In carriers, changes in 5 and 20 μmol/l ADP-induced Aggmax were significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple vs. high-MD group. Fewer patients in the triple group met the criteria of HPPR at 30-day follow-up compared with the high-MD group (2.6% vs. 21.1%, p = 0.014). Conclusions Among AMI patients with CYP2C19 variants, adjunctive cilostazol enhances platelet inhibition and reduces the rate of HPPR, as compared with high-MD clopidogrel. (Adjunctive Cilostazol Versus High-MD ClopidogrEL in Patients With Acute Myocardial Infarction According to CYP2C19 genotype [ACCEL-AMI-CYP2C19]; NCT00915733). Disclosures: No relevant conflicts of interest to declare.

scholarly journals Stent thrombosis in a patient with high on-treatment platelet reactivity despite ticagrelor treatment

2014 ◽  
Vol 4 (1) ◽  
pp. 85-87 ◽  
Author(s):  
Anees Musallam ◽  
Eli I Lev ◽  
Ariel Roguin
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stent Thrombosis ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Loading Dose

We describe, to the best of our knowledge, the first incidence of stent thrombosis in a patient treated with ticagrelor, who exhibited high on-treatment platelet reactivity (HTPR) according to platelet reactivity testing. He was on clopidrogel and tested for platelet reactivity using the VerifyNow P2Y12 assay. The test showed a PRU of 249 and only 12% platelet inhibition. The patient was then switched to ticagrelor, with a loading dose of 180 mg given. The patient had stent thrombosis three weeks later with an acute myocardial infarction (MI). The patient had good platelet inhibition when started on Ticagrelor treatment (PRU=33), but had HTPR when the stent thrombosis occurred three weeks later (PRU=339).

4034Distance from hospital as an early marker of outcomes in out of hospital cardiac arrest acute myocardial infarction survivors treated with endovascular mild therapeutic hypothermia

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Hetclova ◽  
M Hutyra ◽  
J Precek ◽  
O Moravec ◽  
T Skala ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Spontaneous Circulation ◽  
Mild Therapeutic Hypothermia ◽  
Circulation Time ◽  
Left Ventricular Ejection ◽  
Return Of Spontaneous Circulation ◽  
Hospital Cardiac Arrest

Abstract Background The prediction of outcome in comatose patients after out of hospital cardiac arrest (OHCA) has major ethical and socioeconomic implications. At present, there is a lack of data comparing the predictive value from cardiac arrest localization to hospital distance in OHCA survivors treated with endovascular therapeutic hypothermia. Methods 86 patients (64±14 years, 69 men) were evaluated after OHCA due to ventricular fibrillation (VF) during an acute myocardial infarction (MI). All patients (NSTEMI 28%, STEMI 72%) were indicated for urgent coronary angiography, echocardiography for left ventricular ejection fraction (LVEF) estimation using Simpson biplane formula and treated with mild therapeutic hypothermia (MTH) using intravascular temperature management to maintain target temperature (33 °C) for 24 hours. The Cerebral Performance Categories scale (CPC) was used as the outcome measure and was assessed 3 months post admission; a CPC of 3–5 was regarded as a poor outcome (n=45), and a CPC of 1–2 (n=41) as a good outcome. Results Distance to hospital was significantly higher (p=0.0473) in patients with poor outcomes (CPC 3–5) after OHCA (37.5±4.5 km) compared with CPC 1–2 patients (27.1±4.4 km). No significant differences in return of spontaneous circulation time (21; 10.5–47.5 95th percentile vs. 23; 10.0–50.0, p=0.738), lactate (7.8; 4.5–12.4 vs. 8.4; 5.4–13.5, p=0.54), LVEF (40; 22–50 vs. 40; 21–62%, p=0.208), peak cardiac troponin T (1.5; 0.08–10.00 vs. 0.64; 0.04–5.28 μg/L, p=0.078), NSE (29.2; 15.7–54.9 vs. 25.8; 13.6–52.3 μg/L, p=0.26) and S100-B (0.17; 0.09–1.69 vs. 0.19; 0.04–1.14 μg/L, p=0.734) were found in CPC 3–5 and CPC 1–2 groups comparison. Using an optimal cut-off value ≥33 km calculated from the receiver operating characteristic curve (area under curve = 0.62; p=0.004), the sensitivity of predicting survival with poor neurological outcome was 61% and the specificity was 62%. Conclusions In patients after OHCA for VF during MI, distance from cardiac arrest localization to hospital gives reliable and on return of spontaneous circulation time independent prognostic information concerning outcome after cardiopulmonary resuscitation. Acknowledgement/Funding Grant support FNOL RIV 87-85

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