High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

032: Thirty months outcomes after PCI of unprotected left main coronary artery according to the SYNTAX score

AimsTo assess middle term outcomes according to SYNTAX score and rates of delayed surgical/bleeding events after unprotected left main (LM) coronary artery (ULMCA) PCI in an unselected patients population.MethodsConsecutive patients treated by PCI for ULMCA were included among a single center 3508 PCI database within 36 months. Syntax scores were calculated, post discharge extracardiac surgery or hemorrhage were recorded during follow-up as clinical outcomes (Death, TVR, MACCE=cardiovascular death+MI+stroke+TLR).Results102 (3.6%) patients underwent PCI of the LM, including 21 protected LM. Among the 81 patients with PCI of ULMCA, mean age was 65±13, 27% had urgent PCI for AMI or cardiogenic shock, 61% had DES.SYNTAX score was 28±14 in mean and ≤22 in 30 (37%), 23 to 32 in 22 (27%) and ≥33 in 29 (36%) patients.At 30±11 months follow up (98% of the patients), death occurred in 24 patients (30%), TVR in 16 (20%) and MACCE in 35 (43%). Clinical events according to the SYNTAX score are shown in figure. No cardiovascular death occurred in patients with syntax ≤22. MACCE rates were significantly lower when DES were used (24% vs. 64%, p<0.05) and in case of non-urgent PCI (36% vs. 71%, p<0.05).During follow-up, 20 (25%) and 12 (15%) patients underwent unplanned extracardiac surgery and/or hemorrhage, leading to antiplatelet withdrawal in 31% of the cases.ConclusionsIn unselected patients treated by PCI of ULMCA with Syntax score ≤22, outcomes were found to be excellent with no cardiovascular death observed at 30 months. DES and non-urgent PCI were associated with a better prognosis. One patient out of three underwent unplanned extracardiac surgery or hemorrhage during follow up.Figure: 30-months outcomes according to SYNTAX scor

Has the frequency of bleeding changed over time for patients presenting with an acute coronary syndrome? The Global Registry of Acute Coronary Events

AIMS: To determine whether changes in practice, over time, are associated with altered rates of major bleeding in acute coronary syndromes (ACS). METHODS AND RESULTS: Patients from the Global Registry of Acute Coronary Events were enrolled between 2000 and 2007. The main outcome measures were frequency of major bleeding, including haemorrhagic stroke, over time, after adjustment for patient characteristics, and impact of major bleeding on death and myocardial infarction. Of the 50 947 patients, 2.3% sustained a major bleed; almost half of these presented with ST-elevation ACS (44%, 513). Despite changes in antithrombotic therapy (increasing use of low molecular weight heparin, P < 0.0001), thienopyridines (P < 0.0001), and percutaneous coronary interventions (P < 0.0001), frequency of major bleeding for all ACS patients decreased (2.6 to 1.8%; P < 0.0001). Most decline was seen in ST-elevation ACS (2.9 to 2.1%, P = 0.02). The overall decline remained after adjustment for patient characteristics and treatments (P = 0.002, hazard ratio 0.94 per year, 95% confidence interval 0.91-0.98). Hospital characteristics were an independent predictor of bleeding (P < 0.0001). Patients who experienced major bleeding were at increased risk of death within 30 days from admission, even after adjustment for baseline variables. CONCLUSION: Despite increasing use of more intensive therapies, there was a decline in the rate of major bleeding associated with changes in clinical practice. However, individual hospital characteristics remain an important determinant of the frequency of major bleeding

Impact of presentation and transfer delays on complete ST-segment resolution before primary percutaneous coronary intervention: Insights from the ATLANTIC trial

Aims: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial. Methods and results: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as 6570%. Complete STR occurred pre-PCI in 12.8% (204/1, 598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre- PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258). Conclusions: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active. ClinicalTrials.gov Identifier: NCT01347580

Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial

Objective: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. Background: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. Methods: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. Results: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution ( 6570%) after PCI (OR 0.59, 95% CI 0.43\u20130.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62\u20134.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08\u20135.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54\u201328.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. Conclusions: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580

Effect of Pre-Hospital Ticagrelor During the First 24 Hours After Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H Analysis

OBJECTIVES: The aim of this landmark exploratory analysis, ATLANTIC-H24, was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery study). BACKGROUND: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). METHODS: The ATLANTIC-H24 analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction grade 3 flow, >/=70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. RESULTS: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%, p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%, p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%, p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. CONCLUSIONS: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580])