Dataset Information

High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction.

ABSTRACT: Transition from cangrelor to oral P2Y12 inhibitors after PCI carries the risk of platelet function recovery and acute stent thrombosis. Whether the recommended transition regimen is appropriate for hypothermic cardiac arrest survivors is unknown. We assessed the rate of high platelet reactivity (HPR) after transition from cangrelor to ticagrelor in hypothermic cardiac arrest survivors. Adult survivors of out-of-hospital cardiac arrest with ST-segment elevation myocardial infarction (STEMI), who were treated for hypothermia (33 °C ± 1) and received intravenous cangrelor during PCI and subsequent oral loading with 180mg ticagrelor were enrolled in this prospective observational cohort study. Platelet function was assessed using whole blood aggregometry. HPR was defined as AUC > 46U. The primary endpoint was the rate of HPR (%) at predefined time points during the first 24 h after cangrelor cessation. Poisson regression was used to estimate the relationship between the overlap time of cangrelor and ticagrelor co-administration and the number of subsequent HPR episodes, expressed as incidence rate ratio (IRR) with 95% confidence interval (95%CI). Between December 2017 and October 2019 16 patients (81% male, 58 years) were enrolled. On average, ticagrelor was administered 39 min (IQR 5-50) before the end of cangrelor infusion. The rate of HPR was highest 90 min after cangrelor cessation and was present in 44% (7/16) of patients. The number of HPR episodes increased significantly with decreasing overlap time of cangrelor and ticagrelor co-administration (IRR 1.03, 95%CI 1.01-1.05; p = 0.005). In this selected cohort of hypothermic cardiac arrest survivors who received cangrelor during PCI, ticagrelor loading within the recommended time frame before cangrelor cessation resulted in a substantial amount of patients with HPR.

SUBMITTER: Buchtele N

PROVIDER: S-EPMC7073541 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction.

Buchtele Nina N Herkner Harald H Schörgenhofer Christian C Merrelaar Anne A Laggner Roberta R Gelbenegger Georg G Spiel Alexander O AO Domanovits Hans H Lang Irene I Jilma Bernd B Schwameis Michael M

Journal of clinical medicine 20200221 2

Transition from cangrelor to oral P2Y12 inhibitors after PCI carries the risk of platelet function recovery and acute stent thrombosis. Whether the recommended transition regimen is appropriate for hypothermic cardiac arrest survivors is unknown. We assessed the rate of high platelet reactivity (HPR) after transition from cangrelor to ticagrelor in hypothermic cardiac arrest survivors. Adult survivors of out-of-hospital cardiac arrest with ST-segment elevation myocardial infarction (STEMI), who ...[more]

PMID: 32098088

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Project description:Importance:Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Objective:To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. Design, Setting, and Participants:A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. Interventions:Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main Outcomes and Measures:P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results:Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P?=?.26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P?=?.003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P?=?.005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P?=?.30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P?=?.001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P?=?.005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P?=?.24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P?>?.99). Conclusions and Relevance:Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. Trial Registration:clinicaltrials.gov Identifier: NCT02725099.

Project description:IntroductionAmong patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and morphine received on ticagrelor pharmacodynamic and pharmacokinetic responses in patients with STEMI remains however undetermined.Materials and methodsWe performed a post-hoc subanalysis of the prospective, open-label, single-center, randomized PERSEUS trial (NCT02531165) that compared treatment with intravenous fentanyl vs. morphine among symptomatic patients with STEMI treated with primary PCI after ticagrelor pretreatment. Patients from the same population as PERSEUS were further stratified according to the total dose of intravenous opioids received. The primary outcome was platelet reactivity using P2Y12 reaction units (PRU) at 2 h following administration of a loading dose (LD) of ticagrelor. Secondary outcomes were platelet reactivity and peak plasma levels of ticagrelor and AR-C124910XX, its active metabolite, at up to 12 h after ticagrelor LD administration. Generalized linear models for repeated measures were built to determine the relationship between raw and weight-weighted doses of fentanyl and morphine.Results38 patients with STEMI were included between December 18, 2015, and June 22, 2017. Baseline clinical and procedural characteristics were similar between low- and high-dose opioid subgroups. At 2 h, there was a significant correlation between PRU and both raw [regression coefficient (B), 0.51; 95% confidence interval (CI), 0.02-0.99; p = 0.043] and weight-weighted (B, 0.54; 95% CI, 0.49-0.59; p < 0.001) doses of fentanyl, but not morphine. Median PRU at 2 h was significantly lower in patients receiving low, as compared to high, doses of fentanyl [147; interquartile range (IQR), 63-202; vs. 255; IQR, 183-274; p = 0.028], whereas no significant difference was found in those receiving morphine (217; IQR, 165-266; vs. 237; IQR, 165-269; p = 0.09). At 2 h, weight-weighted doses of fentanyl and morphine were significantly correlated to plasma levels of ticagrelor and AR-C124910XX.ConclusionIn symptomatic patients with STEMI who underwent primary PCI after ticagrelor pretreatment and who received intravenous opioids, we found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition.

Project description:Background Current guidelines recommend the new-generation P2Y12-inhibitor ticagrelor for patients with acute ST-segment-elevation myocardial infarctions (STEMIs). The aim of the present study was to assess efficacy and safety of ticagrelor for elderly patients with STEMI (?75 years) in an all-comers STEMI registry. Methods and Results Patients with STEMI, aged ?75 years, treated with primary percutaneous coronary intervention and documented in the Bremen STEMI Registry between 2006 and 2017 entered analysis. The primary efficacy outcome, major adverse cardiac and cerebrovascular events, was defined as a composite of death, myocardial reinfarction, and stroke. The safety outcome was defined as any significant bleeding event within 1 year. To estimate benefit/risk ratio, net adverse clinical events (major adverse cardiac and cerebrovascular events+bleedings) were calculated. Outcomes were estimated in propensity score-matched cohorts to adjust for possible confounders. Of a total of 7466 patients with STEMI, 1087, aged ?75 years, were selected, of which 552 (51%) received clopidogrel and 535 (49%) received ticagrelor, with similar age (80.9±4.6 versus 80.9±4.6 years) and sex (51% versus 50% female) distributions between treatment arms. The primary efficacy outcome occurred in 32.4% of patients treated with clopidogrel versus 25.5% treated with ticagrelor (P=0.015), with the 1-year mortality rate at 26.8% versus 21.1% (P=0.035). Because there was no difference in the safety outcome (clopidogrel versus ticagrelor, 4.9% versus 5.1%; not significant), net adverse clinical events were higher for clopidogrel than for ticagrelor: 37.3% versus 30.6% (P=0.028). In a propensity score-matched model, the advantage for ticagrelor on major adverse cardiac and cerebrovascular events remained significant (hazard ratio, 0.69; 95% CI, 0.49-0.97; P=0.03), whereas 1-year-mortality (hazard ratio, 0.89; 95% CI, 0.67-1.27; P=0.5) and 1-year bleeding events (hazard ratio, 1.1; 95% CI, 0.4-2.3; P=0.8) did not differ. Conclusions These results from propensity score-matched registry data show that for elderly patients with STEMI, ticagrelor compared with clopidogrel was associated with a reduction in major adverse cardiac and cerebrovascular events without a significant increase in bleeding events within 1 year.

Dataset Information

High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction.

Publications

High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction.

Similar Datasets

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