Prehospital crushed versus integral prasugrel loading dose in STEMI patients with a large myocardial area.

BACKGROUND: The effect of administering a crushed prasugrel loading dose is uncertain in patients presenting with a large myocardial infarction and ST-segment elevation myocardial infarction (STEMI). AIMS: The aim of this study was to investigate if patients with a large myocardial infarction may benefit from prehospital administration of a crushed prasugrel loading dose. METHODS: Patients from the CompareCrush trial with an available ambulance electrocardiography (ECG) were included in the study. An independent core laboratory confirmed a prehospital large myocardial area. We compared pre- and postprocedural angiographic markers, including Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, high thrombus burden, and myocardial blush grade 3, in STEMI patients with and without a prehospital large myocardial area. RESULTS: Ambulance ECG was available for 532 patients, of whom 331 patients were identified with a prehospital large myocardial area at risk. Crushed prasugrel significantly improved postprocedural TIMI 3 flow rates in STEMI patients with a prehospital large myocardial area at risk (92% vs 79%, odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.50-6.00) but not in STEMI patients without a prehospital large myocardial area at risk (91% vs 95%, OR 0.47, 95% CI: 0.14-1.57; pinteraction=0.009). CONCLUSIONS: Administration of crushed prasugrel may improve postprocedural TIMI 3 flow in STEMI patients with signs of a large myocardial area at risk on the ambulance ECG. The practice of crushing tablets of prasugrel loading dose might, therefore, represent a safe, fast and cost-effective strategy to improve myocardial reperfusion in this high-risk STEMI subgroup undergoing primary percutaneous coronary intervention.

Assessment of the Diagnostic Accuracy and Reliability of the HEART Score Calculated by Ambulance Nurses Versus Emergency Physicians.

Chest pain is a common complaint for consultation of emergency medical services worldwide. Currently, ambulance nurses (AN) base their decision to transport a patient to the hospital on their own professional experience. The HEART score could improve prehospital risk stratification and patient treatment. The aim of this study is to investigate the interrater reliability and predictive accuracy of the HEART score between AN and emergency physicians (EP). A retrospective analysis on data of 569 patients 18 years and older included in two prehospital HEART score studies. The endpoints are interrater reliability (intraclass correlation [ICC]) and predictive accuracy for major adverse cardiac events within 30 days of the HEART score calculated by AN versus EP. Predictive accuracy is sensitivity, specificity, positive predicted value (PPV) and negative predicted value (NPV). Interrater reliability was good for total HEART score (ICC 0.78; 95% CI 0.75-0.81). However, focusing on the decision to transport a patient, the ICC dropped to 0.62 (95% CI 0.62-0.70). History and Risk factors caused the most variability. Predictive accuracy of HEART differed between AN and EP. The HEART score calculated by AN was sensitivity 91%, specificity 38%, PPV 26%, and NPV 95%. The HEART score calculated by EP was sensitivity 98%, specificity 32%, PPV -26%, and NPV 99%. With a cut-off value of 0-2 for a low HEART score, predictive accuracy significantly improved for the HEART score calculated by AN: sensitivity 98%, specificity 18%, PPV 22%, and NPV 98%. Our study shows a moderate interrater reliability and lower predictive accuracy of a HEART score calculated by AN versus EP. AN underestimate the risk of patients with acute chest pain, with the largest discrepancies in the elements History and Risk factors. Reconsidering the cut-off values of the low-risk HEART category, as well as a carefully developed training program, will possibly lead to a higher interrater reliability of the HEART score and higher predictive accuracy used by AN.

Direct Stenting versus Conventional Stenting in Patients with ST-Segment Elevation Myocardial Infarction-A COMPARE CRUSH Sub-Study.

BACKGROUND: Direct stenting (DS) compared with conventional stenting (CS) after balloon predilatation may reduce distal embolization during percutaneous coronary intervention (PCI), thereby improving tissue reperfusion. In contrast, DS may increase the risk of stent underexpansion and target lesion failure. METHODS: In this sub-study of the randomized COMPARE CRUSH trial (NCT03296540), we reviewed the efficacy of DS versus CS in a cohort of contemporary, pretreated ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. We compared DS versus CS, assessing (1) stent diameter in the culprit lesion, (2) thrombolysis in myocardial infarction (TIMI) flow in the infarct-related artery post-PCI and complete ST-segment resolution (STR) one-hour post-PCI, and (3) target lesion failure at one year. For proportional variables, propensity score weighting was applied to account for potential treatment selection bias. RESULTS: This prespecified sub-study included 446 patients, of whom 189 (42%) were treated with DS. Stent diameters were comparable between groups (3.2 ± 0.5 vs. 3.2 ± 0.5 mm, p = 0.17). Post-PCI TIMI 3 flow and complete STR post-PCI rates were similar between groups (DS 93% vs. CS 90%, adjusted OR 1.16 [95% CI, 0.56-2.39], p = 0.69, and DS 72% vs. CS 58%, adjusted OR 1.29 [95% CI 0.77-2.16], p = 0.34, respectively). Moreover, target lesion failure rates at one year were comparable (DS 2% vs. 1%, adjusted OR 2.93 [95% CI 0.52-16.49], p = 0.22). CONCLUSION: In this contemporary pretreated STEMI cohort, we found no difference in early myocardial reperfusion outcomes between DS and CS. Moreover, DS seemed comparable to CS in terms of stent diameter and one-year vessel patency.

Patient outcomes before and after implementation of a selective pre-hospital spinal immobilization protocol: A comparative cohort pilot study in a level 2 trauma center.

BACKGROUND: A new selective preventive spinal immobilization (PSI) protocol was introduced in the Netherlands. This may have led to an increase in non-immobilized spinal fractures (NISFs) and consequently adverse patient outcomes. AIM: A pilot study was conducted to describe the adverse patient outcomes in NISF of the PSI protocol change and assess the feasibility of a larger effect study. METHODS: Retrospective comparative cohort pilot study including records of trauma patients with a presumed spinal injury who were presented at the emergency department of a level 2 trauma center by the emergency medical service (EMS). The pre-period 2013-2014 (strict PSI protocol), was compared to the post-period 2017-2018 (selective PSI protocol). Primary outcomes were the percentage of records with a NISF who had an adverse patient outcome such as neurological injuries and mortality before and after the protocol change. Secondary outcomes were the sample size calculation for a larger study and the feasibility of data collection. RESULTS: 1,147 records were included; 442 pre-period, and 705 post-period. The NISF-prevalence was 10% (95% CI 7-16, n = 19) and 8% (95% CI 6-11, n = 33), respectively. In both periods, no neurological injuries or mortality due to NISF were found, by which calculating a sample size is impossible. Data collection showed to be feasible. CONCLUSIONS: No neurological injuries or mortality due to NISF were found in a strict and a selective PSI protocol. Therefore, a larger study is discouraged. Future studies should focus on which patients really profit from PSI and which patients do not.

Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction.

BACKGROUND: The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. METHODS: The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. RESULTS: Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04). CONCLUSIONS: In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation.

Pre-hospital treatment with crushed versus integral tablets of prasugrel in patients presenting with ST-Segment Elevation Myocardial Infarction-1-year follow-up results of the COMPARE CRUSH trial.

The present research letter reports the 1-year clinical outcomes of the randomized COMPARE CRUSH trial, which allocated STEMI patients at first medical contact in the ambulance to receive either crushed or integral tablets of prasugrel loading dose. This trial aimed to investigate whether early enhanced antiplatelet effect constituted by the crushed potent oral P2Y12 inhibitor prasugrel could lead to improved early myocardial reperfusion and clinical outcomes.

Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y12 inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND: Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y12 inhibitor effect is delayed and varies according to formulation administered. METHODS: The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion. RESULTS: A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y12 reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40). CONCLUSIONS: Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.

Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial.

BACKGROUND: Early treatment with a potent oral platelet P2Y12 inhibitor is recommended in patients presenting with ST-segment-elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y12 inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown. METHODS: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment-elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes. RESULTS: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47-70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65-1.30], P=0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78-1.58], P=0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y12 reactivity unit, differed significantly between groups (crushed, 192 [132-245] versus integral, 227 [184-254], P≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days. CONCLUSIONS: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment-elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296540.