Safety of Ticagrelor Compared to Clopidogrel after Prehospital Initiation of Treatment.

Objectives The objective of this registry was to study the safety of prehospital initiation of ticagrelor compared with clopidogrel. Background Ticagrelor has replaced clopidogrel in many hospitals as the routinely used antiplatelet drug in patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, in the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor was associated with an increase in non-CABG (non-coronary artery bypass grafting)-related major bleeding. Data comparing the safety of ticagrelor and clopidogrel after prehospital initiation of treatment are not available. Methods A retrospective, multicenter registry was performed. Selection criteria were the administration of a prehospital loading dose of ticagrelor or clopidogrel according to the ambulance STEMI treatment protocol and the presentation to a percutaneous coronary intervention-capable hospital in our region between January 2011 and December 2012. Follow-up was performed using the electronic patient files for the time period between the antiplatelet loading dose and hospital discharge. The data were analyzed using a primary bleeding end point (any bleeding) and a secondary thrombotic end point (all-cause mortality, spontaneous myocardial infarction, definite stent thrombosis, stroke, or transient ischemic attack). Results Data of 304 clopidogrel-treated and 309 ticagrelor-treated patients were available for analysis. No significant difference in bleeding rate was observed between both groups, using univariate (17.8 vs. 20.1%; p = 0.47; odds ratio, 1.16 [95% confidence interval, 0.78-1.74]) and multivariate ( p = 0.42) analysis. Also for the secondary thrombotic end point (6.3 vs. 4.9%, p = 0.45), no significant differences were observed. Conclusion In this real-world registry, no significant differences in bleeding or thrombotic event rate were found between ticagrelor and clopidogrel after prehospital initiation of treatment.

Per-Protocol and Pre-Defined population analysis of the LINC study.

OBJECTIVE: To perform two predefined sub-group analyses within the LINC study and evaluate if the results were supportive of the previous reported intention to treat (ITT) analysis. METHODS: Predefined subgroup analyses from the previously published LINC study were performed. The Per-Protocol population (PPP) included the randomized patients included in the ITT-population but excluding those with violated inclusion or exclusion criteria and those that did not get the actual treatment to which the patient was randomized. In the Pre-Defined population (PDP) analyses patients were also excluded if the dispatch time to ambulance arrival at the address exceeded 12 min, there was a non-witnessed cardiac arrest, or if it was not possible to determine whether the arrest was witnessed or not, and those cases where LUCAS was not brought to the scene at the first instance. RESULTS: After exclusion from the 2589 patients within the ITT-population, the Per-Protocol analysis was performed in 2370 patients and the Pre-Defined analysis within 1133 patients. There was no significant difference in 4-h survival of patients between the mechanical-CPR group and the manual-CPR group in the Per-Protocol population; 279 of 1172 patients (23.8%) versus 281 of 1198 patients (23.5%) (risk difference -0.35%, 95% C.I. -3.1 to 3.8, p=0.85) or in the Pre-Defined population; 176 of 567 patients (31.0%) versus 192 of 566 patients (33.9%) (risk difference -2.88%, 95% C.I. -8.3 to 2.6, p=0.31). There was no difference in any of the second outcome variables analyzed in the Pre-Protocol or Pre-Defined populations. CONCLUSIONS: The results from these predefined sub-group analyses of the LINC study population did not show any difference in 4h survival or in secondary outcome variables between patients treated with mechanical-CPR or manual-CPR. This is consistent with the previously published ITT analysis.

Mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the LINC randomized trial.

IMPORTANCE: A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest, but such a strategy has not been tested in large clinical trials. OBJECTIVE: To determine whether administering mechanical chest compressions with defibrillation during ongoing compressions (mechanical CPR), compared with manual cardiopulmonary resuscitation (manual CPR), according to guidelines, would improve 4-hour survival. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial of 2589 patients with out-of-hospital cardiac arrest conducted between January 2008 and February 2013 in 4 Swedish, 1 British, and 1 Dutch ambulance services and their referring hospitals. Duration of follow-up was 6 months. INTERVENTIONS: Patients were randomized to receive either mechanical chest compressions (LUCAS Chest Compression System, Physio-Control/Jolife AB) combined with defibrillation during ongoing compressions (n = 1300) or to manual CPR according to guidelines (n = 1289). MAIN OUTCOMES AND MEASURES: Four-hour survival, with secondary end points of survival up to 6 months with good neurological outcome using the Cerebral Performance Category (CPC) score. A CPC score of 1 or 2 was classified as a good outcome. RESULTS: Four-hour survival was achieved in 307 patients (23.6%) with mechanical CPR and 305 (23.7%) with manual CPR (risk difference, -0.05%; 95% CI, -3.3% to 3.2%; P > .99). Survival with a CPC score of 1 or 2 occurred in 98 (7.5%) vs 82 (6.4%) (risk difference, 1.18%; 95% CI, -0.78% to 3.1%) at intensive care unit discharge, in 108 (8.3%) vs 100 (7.8%) (risk difference, 0.55%; 95% CI, -1.5% to 2.6%) at hospital discharge, in 105 (8.1%) vs 94 (7.3%) (risk difference, 0.78%; 95% CI, -1.3% to 2.8%) at 1 month, and in 110 (8.5%) vs 98 (7.6%) (risk difference, 0.86%; 95% CI, -1.2% to 3.0%) at 6 months with mechanical CPR and manual CPR, respectively. Among patients surviving at 6 months, 99% in the mechanical CPR group and 94% in the manual CPR group had CPC scores of 1 or 2. CONCLUSIONS AND RELEVANCE: Among adults with out-of-hospital cardiac arrest, there was no significant difference in 4-hour survival between patients treated with the mechanical CPR algorithm or those treated with guideline-adherent manual CPR. The vast majority of survivors in both groups had good neurological outcomes by 6 months. In clinical practice, mechanical CPR using the presented algorithm did not result in improved effectiveness compared with manual CPR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00609778.

Prehospital treatment of ST-segment elevated myocardial infarction patients.

Providing optimal care to patients with ST-segment elevated myocardial infarction is challenging. If a patient experiences chest pain and calls the emergency number, a cascade of actions is initiated that should lead to a diagnosis, start of treatment and reperfusion of the infarcted myocardium. This should all happen within 90 min after first medical contact, irrespective of the location of the patient or the time of day. The complex organization that is needed to achieve this goal in every ST-segment elevated myocardial infarction patient accounts for a fascinating interplay between prehospital and in-hospital care, in a situation when every minute counts. State-of-the-art care should be provided according to the latest insights and guidelines.