Pre-hospital ticagrelor in ST-segment elevation myocardial infarction in the French ATLANTIC population.

BACKGROUND: ATLANTIC was a randomized study comparing pre- and in-hospital treatment with a ticagrelor loading dose (LD) in ongoing ST-segment elevation myocardial infarction (STEMI). We sought to compare patient characteristics and clinical outcomes in France with other countries participating in ATLANTIC. METHODS: The population comprised 1862 patients, 660 (35.4%) from France and 1202 from 12 other countries. The main endpoints were reperfusion (≥70% ST-segment elevation resolution) and TIMI flow grade 3 before (co-primary endpoints) and after percutaneous coronary intervention (PCI). Other endpoints included a composite ischaemic endpoint (death/myocardial infarction/stroke/urgent revascularization/definite stent thrombosis) and bleeding events at 30days. RESULTS: In France, median times from first LD to angiography and between first and second LDs were 49 and 35min, respectively, and were similar to other countries. French patients were younger (mean 58.7 vs 61.9years, p<0.0001) and characterized by a higher rate of radial access (89.9% vs 54.8%, p<0.0001), more frequent use of pre-hospital glycoprotein (GP) IIb/IIIa inhibitors (14.1% vs 3.1%, p<0.0001) and intravenous enoxaparin (57.3% vs 10.1%, p<0.0001). In France, as in other countries, the co-primary endpoints did not differ between the two randomization groups. The composite ischaemic endpoint was numerically lower in France (3.3% vs 5.1%, p=0.07), with a lower mortality (1.4% vs 3.3%, p=0.01). PLATO major bleeding was numerically less frequent in France (1.8% vs 3.2%, p=0.07). CONCLUSIONS: The French population appears to have better outcomes than the rest of the study population, and seems related to differences in demographics and management characteristics. TRIAL REGISTRY: ClinicalTrials.gov (NCT01347580).

One-year incidence and clinical impact of bleeding events in patients treated with prasugrel or clopidogrel after ST-segment elevation myocardial infarction.

BACKGROUND: Little information is available on the long-term incidence of bleeding events after ST-segment elevation myocardial infarction (STEMI) with the current antithrombotic strategy. AIMS: To evaluate the effect of bleedings for up to 12months on clinical events and therapeutic compliance in unselected STEMI patients treated with prasugrel or clopidogrel. METHODS: Patients were treated with clopidogrel or prasugrel according to guidelines. The primary endpoint was first occurrence of a bleeding event from hospital discharge to 12months, assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire. Topography of bleedings, causes of premature cessation and ischaemic events were compared between clopidogrel- and prasugrel-treated patients. RESULTS: A total of 390 patients were enrolled (211 in the prasugrel group, 179 in the clopidogrel group). Elderly, female and low-body weight patients were more likely to receive clopidogrel. At 12months, the incidence of major bleedings (BARC 3) was lower with prasugrel (1% vs 6%; P=0.02), mainly due to fewer transfusions. Elderly age was a risk factor for severe bleeding. Premature treatment cessation was related to ischaemic complications (P=0.03), and occurred more frequently with prasugrel (P=0.001). One-year mortality was very low (1.9 per 100 person-years, 95% confidence interval 0.9-4.0), and was higher in the clopidogrel group (P=0.03). CONCLUSIONS: In this unselected STEMI population, the rate of major bleedings with prasugrel at 12months was low, but nuisance bleedings were frequent and led to more premature cessations than with clopidogrel. Prevention of bleeding complications, even minor, is necessary to prevent disruption of antithrombotic medication.

Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction has traditionally been supported by unfractionated heparin, which has never been directly compared with a new anticoagulant using consistent anticoagulation and similar antiplatelet strategies in both groups. We compared traditional heparin treatment with intravenous enoxaparin in primary PCI. METHODS: In a randomised open-label trial, patients presenting with ST-elevation myocardial infarction were randomly assigned (1:1) to receive an intravenous bolus of 0·5 mg/kg of enoxaparin or unfractionated heparin before primary PCI. Wherever possible, medical teams travelling in mobile intensive care units (ambulances) selected, randomly assigned (using an interactive voice response system at the central randomisation centre), and treated patients. Patients who had received any anticoagulant before randomisation were excluded. Patients and caregivers were not masked to treatment allocation. The primary endpoint was 30-day incidence of death, complication of myocardial infarction, procedure failure, or major bleeding. The main secondary endpoint was the composite of death, recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00718471. FINDINGS: 910 patients were assigned to treatment with enoxaparin (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126 (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on unfractionated heparin (relative risk [RR] 0·83, 95% CI 0·68-1·01, p=0·06). The incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0·08), complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0·21), procedure failure (100 [26%] vs 109 [28%]; p=0·61), and major bleeding (20 [5%] vs 22 [5%]; p=0·79) did not differ between groups. Enoxaparin resulted in a significantly reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR 0·59, 95% CI 0·38-0·91, p=0·015). Death, complication of myocardial infarction, or major bleeding (46 [10%] vs 69 [15%] patients; p=0·03), death or complication of myocardial infarction (35 [8%] vs 57 [12%]; p=0·02), and death, recurrent myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0·04) were all reduced with enoxaparin. INTERPRETATION: Intravenous enoxaparin compared with unfractionated heparin significantly reduced clinical ischaemic outcomes without differences in bleeding and procedural success. Therefore, enoxaparin provided an improvement in net clinical benefit in patients undergoing primary PCI. FUNDING: Direction de la Recherche Clinique, Assistance Publique-Hôpitaux de Paris; Sanofi-Aventis.