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 (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, 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 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, 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.

Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study.

BACKGROUND: Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. METHODS: In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre- versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [≤1 hour (n = 773), >1 to ≤3 hours (n = 772), and >3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. RESULTS: Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC >3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 2.9% vs. >1 to ≤3 hours, 3.6% vs. >3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre- versus in-hospital ticagrelor (absolute risk difference: ≤1 hour, 1.3% vs. >1 hour to ≤3 hours, 0.7% vs. >3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95%CI 1.20-2.97, P < .01), but not post-PCI ST-segment resolution (P = .41). CONCLUSIONS: The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

Prehospital ticagrelor in ST-segment elevation myocardial infarction.

BACKGROUND: The direct-acting platelet P2Y12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. METHODS: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. RESULTS: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used. CONCLUSIONS: Prehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.).

A Clinical Decision Rule to Identify Emergency Department Patients at Low Risk for Acute Coronary Syndrome Who Do Not Need Objective Coronary Artery Disease Testing: The No Objective Testing Rule.

STUDY OBJECTIVE: We derive a clinical decision rule for ongoing investigation of patients who present to the emergency department (ED) with chest pain. The rule identifies patients who are at low risk of acute coronary syndrome and could be discharged without further cardiac testing. METHODS: This was a prospective observational study of 2,396 patients who presented to 2 EDs with chest pain suggestive of acute coronary syndrome and had normal troponin and ECG results 2 hours after presentation. Research nurses collected clinical data on presentation, and the primary endpoint was diagnosis of acute coronary syndrome within 30 days of presentation to the ED. Logistic regression analyses were conducted on 50 bootstrapped samples to identify predictors of acute coronary syndrome. A rule was derived and diagnostic accuracy statistics were computed. RESULTS: Acute coronary syndrome was diagnosed in 126 (5.3%) patients. Regression analyses identified the following predictors of acute coronary syndrome: cardiac risk factors, age, sex, previous myocardial infarction, or coronary artery disease and nitrate use. A rule was derived that identified 753 low-risk patients (31.4%), with sensitivity 97.6% (95% confidence interval [CI] 93.2% to 99.5%), negative predictive value 99.6% (95% CI 98.8% to 99.9%), specificity 33.0% (95% CI 31.1% to 35.0%), and positive predictive value 7.5% (95% CI 6.3% to 8.9%) for acute coronary syndrome. This was referred to as the no objective testing rule. CONCLUSION: We have derived a clinical decision rule for chest pain patients with negative early cardiac biomarker and ECG testing results that identifies 31% at low risk and who may not require objective testing for coronary artery disease. A prospective trial is required to confirm these findings.

External validation of the emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP).

OBJECTIVE: The emergency department assessment of chest pain score accelerated diagnostic pathway (EDACS-ADP) facilitates low-risk ED chest pain patients early to outpatient investigation. We aimed to validate this rule in a North American population. METHODS: We performed a retrospective validation of the EDACS-ADP using 763 chest pain patients who presented to St Paul's Hospital, Vancouver, Canada, between June 2000 and January 2003. Patients were classified as low risk if they had an EDACS <16, no new ischaemia on ECG and non-elevated serial 0-hour and 2-hour cardiac troponin concentrations. The primary outcome was the number of patients who had a predetermined major adverse cardiac event (MACE) at 30 days after presentation. RESULTS: Of the 763 patients, 317 (41.6%) were classified as low risk by the EDACS-ADP. The sensitivity, specificity, negative predictive value and positive predictive value of the EDACS-ADP for 30-day MACE were 100% (95% CI 94.2% to 100%), 46.4% (95% CI 42.6% to 50.2%), 100% (95% CI 98.5% to 100.0%) and 17.5% (95% CI 14.1% to 21.3%), respectively. CONCLUSIONS: This study validated the EDACS-ADP in a novel context and supports its safe use in a North American population. It confirms that EDACS-ADP can facilitate progression to early outpatient investigation in up to 40% of ED chest pain patients within 2 hours.

Survival after an acute coronary syndrome: 18-month outcomes from the Australian and New Zealand SNAPSHOT ACS study.

OBJECTIVES: To assess the impact of the availability of a catheterisation laboratory and evidence-based care on the 18-month mortality rate in patients with suspected acute coronary syndromes (ACS). DESIGN, SETTING AND PARTICIPANTS: Management and outcomes are described for patients enrolled in the 2012 Australian and New Zealand SNAPSHOT ACS audit. Patients were stratified according to their presentation to hospitals with or without cardiac catheterisation facilities. Data linkage ascertained patient vital status 18 months after admission. Descriptive and Cox proportional hazards analyses determined predictors of outcomes, and were used to estimate the numbers of deaths that could be averted by improved application of evidence-based care. MAIN OUTCOME MEASURES: Mortality for ACS patients from admission to 18 months after admission. RESULTS: Definite ACS patients presenting to catheterisation-capable (CC) hospitals (n = 1326) were more likely to undergo coronary angiography than those presenting to non-CC hospitals (n = 1031) (61.5% v 50.8%; P = 0.0001), receive timely reperfusion (for ST elevation myocardial infarction (STEMI) patients: 45.2% v 19.2%; P < 0.001), and be referred for cardiac rehabilitation (57% v 53%; P = 0.05). All-cause mortality over 18 months was highest for STEMI (16.2%) and non-STEMI (16.3%) patients, and lowest for those presenting with unstable angina (6.8%) and non-cardiac chest pain (4.8%; P < 0.0001 for trend). After adjustment for patient propensity to present to a CC hospital and patient risk, presentation to a CC hospital was associated with 21% (95% CI, 2%-37%) lower mortality than presentation to a non-CC hospital. This mortality difference was attenuated after adjusting for delivery of evidence-based care. CONCLUSION: In Australia and New Zealand, the availability of a catheterisation laboratory appears to have a significant impact on long-term mortality in ACS patients, which is still substantial. This mortality may be reduced by improvements in evidence-based care in both CC and non-CC hospitals.

Cost and outcomes of assessing patients with chest pain in an Australian emergency department.

OBJECTIVES: We sought to characterise the demographics, length of admission, final diagnoses, long-term outcome and costs associated with the population who presented to an Australian emergency department (ED) with symptoms of possible acute coronary syndrome (ACS). DESIGN, SETTING AND PARTICIPANTS: Prospectively collected data on ED patients presenting with suspected ACS between November 2008 and February 2011 was used, including data on presentation and at 30 days after presentation. Information on patient disposition, length of stay and costs incurred was extracted from hospital administration records. MAIN OUTCOME MEASURES: Primary outcomes were mean and median cost and length of hospital stay. Secondary outcomes were diagnosis of ACS, other cardiovascular conditions or non-cardiovascular conditions within 30 days of presentation. RESULTS: An ACS was diagnosed in 103 (11.1%) of the 926 patients recruited. 193 patients (20.8%) were diagnosed with other cardiovascular-related conditions and 622 patients (67.2%) had non-cardiac-related chest pain. ACS events occurred in 0 and 11 (1.9%) of the low-risk and intermediate-risk groups, respectively. Ninety-two (28.0%) of the 329 high-risk patients had an ACS event. Patients with a proven ACS, high-grade atrioventricular block, pulmonary embolism and other respiratory conditions had the longest length of stay. The mean cost was highest in the ACS group ($13 509; 95% CI, $11 794-$15 223) followed by other cardiovascular conditions ($7283; 95% CI, $6152-$8415) and non-cardiovascular conditions ($3331; 95% CI, $2976-$3685). CONCLUSIONS: Most ED patients with symptoms of possible ACS do not have a cardiac cause for their presentation. The current guideline-based process of assessment is lengthy, costly and consumes significant resources. Investigation of strategies to shorten this process or reduce the need for objective cardiac testing in patients at intermediate risk according to the National Heart Foundation and Cardiac Society of Australia and New Zealand guideline is required.

Availability of highly sensitive troponin assays and acute coronary syndrome care: insights from the SNAPSHOT registry.

OBJECTIVES: To examine differences in care and inhospital course of patients with possible acute coronary syndrome (ACS) in Australia and New Zealand based on whether a highly sensitive (hs) troponin assay was used at the hospital to which they presented. DESIGN, SETTING AND PATIENTS: A snapshot study of consecutive patients presenting to hospitals in Australia and New Zealand from 14 to 27 May 2012 with possible ACS. MAIN OUTCOME MEASURES: Rates of major adverse cardiac events (inhospital death, new or recurrent myocardial infarction, stroke, cardiac arrest or worsening heart failure); association between assay type and outcome (via propensity score matching and a generalised estimating equation [GEE]; averages of the predicted outcomes among patients who were treated with and without the availability of an hs assay (via inverse probability-weighting [IPW] with regression-adjusted estimators). RESULTS: 4371 patients with possible ACS were admitted to 283 hospitals. Over half of the hospitals (156 [55%]) reported using the hs assay and most patients (2624 [60%]) had hs tests (P = 0.004). Use of the hs assay was independent of hospital coronary revascularisation capability. Patients tested with the hs assay had more non-invasive investigations (exercise tests, stress echocardiography, stress nuclear scans, and computed tomography coronary angiography) than those tested with the sensitive assay. However, there were no differences between the groups in rates of angiography or revascularisation. All adjusted analyses showed a consistently lower rate of inhospital events, including recurrent heart failure in patients for whom the hs assay was used (GEE odds ratio, 0.75; 95% CI, 0.60-0.94; P = 0.014); IPW analysis showed a 2.3% absolute reduction in these events with the use of the hs assay (P = 0.018). CONCLUSION: Use of hs troponin testing of patients hospitalised with possible ACS was associated with an increased rate of non-invasive cardiac investigations and fewer inhospital adverse events.

Should fee-for-service be for all guideline-advocated acute coronary syndrome (ACS) care? Observations from the Snapshot ACS study.

OBJECTIVE: The aim of the present study was to explore the association of health insurance status on the provision of guideline-advocated acute coronary syndrome (ACS) care in Australia. METHODS: Consecutive hospitalisations of suspected ACS from 14 to 27 May 2012 enrolled in the Snapshot study of Australian and New Zealand patients were evaluated. Descriptive and logistic regression analysis was performed to evaluate the association of patient risk and insurance status with the receipt of care. RESULTS: In all, 3391 patients with suspected ACS from 247 hospitals (23 private) were enrolled in the present study. One-third of patients declared private insurance coverage; of these, 27.9% (304/1088) presented to private facilities. Compared with public patients, privately insured patients were more likely to undergo in-patient echocardiography and receive early angiography; furthermore, in those with a discharge diagnosis of ACS, there was a higher rate of revascularisation (P < 0.001). Each of these attracts potential fee-for-service. In contrast, proportionately fewer privately insured ACS patients were discharged on selected guideline therapies and were referred to a secondary prevention program (P = 0.056), neither of which directly attracts a fee. Typically, as GRACE (the Global Registry of Acute Coronary Events) risk score rose, so did the level of ACS care; however, propensity-adjusted analyses showed lower in-hospital adverse events among the insured group (odds ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.004). CONCLUSION: Fee-for-service reimbursement may explain differences in the provision of selected guideline-advocated components of ACS care between privately insured and public patients.

Validation of an accelerated high-sensitivity troponin T assay protocol in an Australian cohort with chest pain.

OBJECTIVES: To validate an accelerated biomarker strategy using a high-sensitivity cardiac troponin T (hs-cTnT) assay for diagnosing acute myocardial infarction (AMI) in patients presenting to the emergency department with chest pain; and to validate this strategy in combination with the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand risk stratification model. DESIGN, SETTING AND PATIENTS: Single-centre, prospective, observational cohort study of 764 adults presenting to a tertiary hospital with symptoms of possible acute coronary syndrome between November 2008 and February 2011. MAIN OUTCOME MEASURES: AMI or cardiac death within 24 hours of presentation (primary), and major adverse cardiac events within 30 days (secondary). RESULTS: An elevated hs-cTnT assay result above the 99th percentile at either the 0 h or 2 h time points had sensitivity of 96.4% (95% CI, 87.9%-99.0%), specificity of 82.6% (95% CI, 79.7%-85.2%), negative predictive value of 99.7% (95% CI, 98.8%-99.9%) and positive predictive value of 30.5% (95% CI, 24.2%-37.6%) for diagnosing AMI. Compared with a traditional 6 h cardiac troponin testing strategy, the accelerated strategy led to reclassification of risk in only two patients with adverse cardiac outcomes, with no net effect on appropriate management. CONCLUSIONS: In patients presenting with chest pain, an accelerated biomarker strategy using the hs-cTnT assay performed well in the initial diagnosis of AMI. The accelerated strategy was also effective when incorporated into a comprehensive strategy of risk stratification that included clinical and demographic factors. The time saved by this approach could have a major impact on health service delivery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000053022.