Lutz Nibbe

Bivalirudin started during emergency transport for primary PCI

BACKGROUND Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.).

Bivalirudin is superior to heparins alone with bailout GP IIb/IIIa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX trial

Aims In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention (PCI) compared with heparin and routine glycoprotein IIb/IIIa inhibitors (GPI). It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout. Methods and results In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction (STEMI) were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or non-CABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin (n = 1089) with those receiving heparins with routine upstream GPI (n = 649) and those receiving heparins only with GPI use restricted to bailout (n = 460). The primary outcome death and major bleeding occurred in 5.1% with bivalirudin, 7.6% with heparin plus routine GPI (HR 0.67 and 95% CI 0.46–0.97, P = 0.034), and 9.8% with heparins plus bailout GPI (HR 0.52 and 95% CI 0.35–0.75, P = 0.006). Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome (odds ratio 0.53, 95% CI 0.33–0.87) and major bleeding (odds ratio 0.44, 95% CI 0.24–0.82) compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin (1.6 vs. 0.6 vs. 0.4%, P = 0.09 and 0.09). Conclusion Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.

Pre-hospital treatment of STEMI patients. A scientific statement of the working group acute cardiac care of the European society of cardiology

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patients delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patients baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Reperfusion rate and inhospital mortality of patients with ST segment elevation myocardial infarction diagnosed already in the prehospital phase: Results of the German Prehospital Myocardial Infarction Registry (PREMIR)

AIMS We sought to evaluate the in-hospital fate of patients with ST segment elevation myocardial infarction (STEMI) diagnosed already in the prehospital phase by physican equipped ambulances. METHODS A total of 2326 consecutive STEMI patients were included in PREMIR. For this analysis 218 patients with prehospital cardiopulmonary resuscitation were excluded. RESULTS The median time between symptom onset and 12-lead ECG was 85 min. The median time intervals between the diagnostic 12-lead ECG and prehospital fibrinolysis were 10 min, until inhospital fibrinolysis 52 min and until primar PCI 86min, respectively. Reperfusion therapy with prehospital fibrinolysis (24%), inhospital fibrinolysis (13%) or primary PCI (45%) was performed in 82% of the patients. Inhospital mortality was 6.0% in patients with prehospital fibrinolysis (n = 504), 5.8% in patients with inhospital fibrinolysis (n = 278), 4.5% in patients with primary percutaneous coronary intervention (n = 962) and 16.2% in patients without early reperfusion therapy (n = 377), respectively. In the multivariate propensity score analysis comparing prehospital fibrinolysis and primary PCI we observed no significant difference in the odds for in-hospital mortality (odds ratio: 1.57, 95% CI: 0.94-2.63). The final discharge diagnosis was STEMI in 90% of the patients, in patients with prehospital fibrinolysis 95%. CONCLUSIONS In patients with STEMI already diagnosed in the prehospital phase the ischemic time is short, accuracy of the diagnosis is high and reperfusion therapy is performed in over 82%. Inhospital mortality was not different between prehospital fibrinolysis and primary PCI.

Therapeutic hypothermia after cardiac arrest – the implementation of the ILCOR guidelines in clinical routine is possible!

Therapeutic hypothermia after cardiac arrest is a treatment with a high level of evidence. In 2003 the International Liaison Committee on Resuscitation (ILCOR) recommended such treatment for all comatose survivors of out-of-hospital cardiac arrest when the initial rhythm was ventricular fibrillation [1]. However, recent studies have shown that only a minority of resuscitated patients are treated with therapeutic hypothermia in both American and European intensive care units [2-4]. A letter recently published in Critical Care reported the use of therapeutic hypothermia in Germany in only 38% of departments treating patients after cardiac arrest [5]. To improve adherence to the ILCOR guidelines we developed a written standard operating procedure (SOP) for patients after cardiac arrest admitted to our 38-bed medical intensive care unit. Starting in December 2005 the SOP was to be applied to all comatose patients after cardiac arrest, irrespective of the initial rhythm. Since then the SOP has been applied in 28 out of 34 eligible patients. For four patients the physician in charge did not consider therapeutic hypothermia despite clear indication. In two other patients hypothermia was considered to be contraindicated because of extensive coronary vasospasm or massive pulmonary bleeding of a bronchial carcinoma, respectively. In all the remaining 28 patients surface cooling with technical devices (CritiCool from MTRE, Yavne Israel, and ArcticSun from Medivance, Louisville, KY, USA) was used to induce and maintain hypothermia for 24 hours. The target temperature of 33°C was reached in 6.0 ± 3.2 hours (mean ± SD). In none of the patients were serious adverse events potentially related to therapeutic hypothermia, such as clinically relevant bleeding episodes or arrhythmias, observed. In 12 out of 28 patients (42.9%) treated with therapeutic hypothermia a favourable neurologic outcome was reached (Cerebral Performance Category 1 or 2). Although our limited experience does not yet permit a valid statistical evaluation of the impact of therapeutic hypothermia on the neurological outcome of the patients, initial results are encouraging. We are currently trying to shorten the time to target temperature, which we feel was still too long in some patients. However, the simple availability of a written SOP has already led to the application of therapeutic hypothermia in the vast majority of our patients after cardiac arrest. All physicians caring for such patients should be encouraged to establish their own protocol for therapeutic hypothermia at their institutions, to facilitate the widespread application of this evidence-based treatment.

Fate of Patients With Prehospital Resuscitation for ST-Elevation Myocardial Infarction and a High Rate of Early Reperfusion Therapy (Results from the PREMIR [Prehospital Myocardial Infarction Registry])

Patients with acute ST-segment elevation myocardial infarction (STEMI) needing prehospital cardiopulmonary resuscitation (CPR) have a very high adverse-event rate. However, little is known about the fate of these patients and predictors of mortality in the era of early reperfusion therapy. From March 2003 through December 2004, 2,317 patients with prehospital diagnosed STEMI were enrolled in the Prehospital Myocardial Infarction Registry. One hundred ninety patients (8.2%) underwent prehospital CPR and were included in our analysis. Overall 90% of patients were treated with early reperfusion therapy, 56.3% received prehospital thrombolysis and 1/2 of these patients received early percutaneous coronary intervention after thrombolysis, 28.4% of patients were treated with primary percutaneous coronary intervention, and 5.3% received in-hospital thrombolysis. Total mortality was 40.0%. The highest mortality was seen in patients with asystole (63%) or pulseless electric activity (64%). Independent predictors of mortality were need for endotracheal intubation and older age, whereas ventricular fibrillation as initial heart rhythm was associated with survival. In conclusion, in this large registry with prehospital diagnosed STEMI, incidence of prehospital CPR was about 8%. Even with a very high rate of early reperfusion therapy, in-hospital mortality was high. Especially in elderly patients with asystole as initial heart rhythm and with need for endotracheal intubation, prognosis is poor despite aggressive reperfusion therapy.

Design and methods of European Ambulance Acute Coronary Syndrome Angiography Trial (EUROMAX): An international randomized open-label ambulance trial of bivalirudin versus standard-of-care anticoagulation in patients with acute ST-segment-elevation myocardial infarction transferred for primary percutaneous coronary intervention

BACKGROUND In patients with ST-segment elevation myocardial infarction (STEMI) triaged to primary percutaneous coronary intervention (PCI), anticoagulation often is initiated in the ambulance during transfer to a PCI site. In this prehospital setting, bivalirudin has not been compared with standard-of-care anticoagulation. In addition, it has not been tested in conjunction with the newer P2Y12 inhibitors prasugrel or ticagrelor. DESIGN EUROMAX is a randomized, international, prospective, open-label ambulance trial comparing bivalirudin with standard-of-care anticoagulation with or without glycoprotein IIb/IIIa inhibitors in 2200 patients with STEMI and intended for primary percutaneous coronary intervention (PCI), presenting either via ambulance or to centers where PCI is not performed. Patients will receive either bivalirudin given as a 0.75 mg/kg bolus followed immediately by a 1.75-mg/kg per hour infusion for ≥30 minutes prior to primary PCI and continued for ≥4 hours after the end of the procedure at the reduced dose of 0.25 mg/kg per hour, or heparins at guideline-recommended doses, with or without routine or bailout glycoprotein IIb/IIIa inhibitor treatment according to local practice. The primary end point is the composite incidence of death or non-coronary-artery-bypass-graft related protocol major bleeding at 30 days by intention to treat. CONCLUSION The EUROMAX trial will test whether bivalirudin started in the ambulance and continued for 4 hours after primary PCI improves clinical outcomes compared with guideline-recommended standard-of-care heparin-based regimens, and will also provide information on the combination of bivalirudin with prasugrel or ticagrelor.

Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin. A position paper of the Acute Cardiovascular Care Association (ACCA) of the ESC.

Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts’ opinions, for all emergency medical services’ health providers involved in the pre-hospital management of acute cardiovascular care.

A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report

IntroductionA rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction.Case presentationA 22-year-old Caucasian man was admitted unconscious with a body temperature of 42°C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000®, Medivance Inc., USA), originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa®) for schizophrenia.ConclusionNumerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa®) medication. Frequently hyperthermia has been observed in these cases with varying outcomes. In our case the only residual impairment for the patient is dysarthria with corresponding symmetric cerebellar pyramidal cell destruction demonstrated by increased signal intensity in T2-weighted magnetic resonance imaging, most likely caused by the excessive hyperthermia.

Verbesserung der Zusammenarbeit zwischen Notärzten und Kardiologen zur Optimierung der frühen Therapie bei akutem ST-Hebungs-Infarkt

ZusammenfassungBei ST-Hebungs-Infarkt ist das Ziel, die Zeit bis zur Reperfusion zu verringern. Neben verspäteter Alarmierung des Notarztes gibt es auch häufig Zeitverluste, weil die vom Notarzt gestellte Diagnose im Krankenhaus in Zweifel gezogen wird und daher Befunde neu erhoben werden. Vertrauensbildende Maßnahmen wie gemeinsame Workshops von Kardiologen und Notärzten können zu einer besseren Kooperation beitragen. Ein weiteres Problem ist die Finanzierung der prähospitalen Lyse. Diese früh einsetzende Therapie kann die Prognose von Patienten mit akutem ST-Hebungs-Infarkt verbessern. Doch bisher ist die Kostenübernahme dafür nicht geklärt.AbstractIn cases of ST elevation myocardial infarction (MI), the aim is to reduce the time to reperfusion. Together with delay in contacting the emergency doctor, time is also commonly lost because the emergency site diagnosis is often queried in the hospital and a new diagnosis made. Building trust between cardiologists and emergency doctors, such as at common workshops, can lead to better cooperation. Another problem is the financing of prehospital thrombolysis. This early therapy can improve the prognosis for patients with acute ST elevation MI. However, the cost carrier has not yet been clearly determined.