Differences between sexes in STEMI treatment and outcomes with contemporary primary PCI.

BACKGROUND: Historically, differences in timely reperfusion and outcomes have been described in females who suffer ST-segment elevation myocardial infarction (STEMI). However, there have been improvements in the treatment of STEMI patients with contemporary Percutaneous Coronary Intervention (PCI) strategies. METHODS: Comparisons between sexes were performed on STEMI patients treated with primary PCI over a 4-year period (January 1, 2017-December 31, 2020) from the Queensland Cardiac Outcomes Registry. Primary outcomes were 30-day and 1-year cardiovascular mortality. Secondary outcomes were STEMI performance measures. The total and direct effects of gender on mortality outcomes were estimated using logistic and multinomial logistic regression models. RESULTS: Overall, 2747 (76% male) were included. Females were on average older (65.9 vs. 61.9 years; p < 0.001), had longer total ischemic time (69 min vs. 52 min; p < 0.001) and less achievement of STEMI performance targets (<90 min) (50% vs. 58%; p < 0.001). There was no evidence for a total (odds ratio [OR] 1.3 (95% confidence interval [CI]: 0.8-2.2; p = 0.35) or direct (adjusted OR 1.2 (95% CI: 0.7-2.1; p = 0.58) effect of female sex on 30-day mortality. One-year mortality was higher in females (6.9% vs. 4.4%; p = 0.014) with total effect estimates consistent with increased risk of cardiovascular mortality (Incidence rate ratio [IRR]: 1.5; 95% CI: 1.0-2.3; p = 0.059) and noncardiovascular mortality (IRR: 2.1; 95% CI: 0.9-4.7; p = 0.077) in females. However, direct (adjusted) effect estimates of cardiovascular mortality (IRR: 1.0; 95% CI: 0.6-1.6; p = 0.94) indicated sex differences were explained by confounders and mediators. CONCLUSION: Small sex differences in STEMI performance measures still exist; however, with contemporary primary PCI strategies, sex is not associated with cardiovascular mortality at 30 days or 1 year.

Asundexian versus Apixaban in Patients with Atrial Fibrillation.

BACKGROUND: Stroke prevention with direct-acting oral anticoagulant agents in patients with atrial fibrillation confers a risk of bleeding and limits their use. Asundexian, an activated factor XI (XIa) inhibitor, is an oral anticoagulant that may prevent strokes with less bleeding. METHODS: In a phase 3, international, double-blind trial, we randomly assigned high-risk patients with atrial fibrillation in a 1:1 ratio to receive asundexian at a dose of 50 mg once daily or standard-dose apixaban. The primary efficacy objective was to determine whether asundexian is at least noninferior to apixaban for the prevention of stroke or systemic embolism. The primary safety objective was to determine whether asundexian is superior to apixaban with respect to major bleeding events. RESULTS: A total of 14,810 randomly assigned patients were included in the intention-to-treat population. The mean (±SD) age of the patients was 73.9±7.7 years, 35.2% were women, 18.6% had chronic kidney disease, 18.2% had a previous stroke or transient ischemic attack, 16.8% had received oral anticoagulants for no more than 6 weeks, and the mean CHA2DS2-VASc score (range, 0 to 9, with higher scores indicating a greater risk of stroke) was 4.3±1.3. The trial was stopped prematurely at the recommendation of the independent data monitoring committee. Stroke or systemic embolism occurred in 98 patients (1.3%) assigned to receive asundexian and in 26 (0.4%) assigned to receive apixaban (hazard ratio, 3.79; 95% confidence interval [CI], 2.46 to 5.83). Major bleeding occurred in 17 patients (0.2%) who received asundexian and in 53 (0.7%) who received apixaban (hazard ratio, 0.32; 95% CI, 0.18 to 0.55). The incidence of any adverse event appeared to be similar in the two groups. CONCLUSIONS: Among patients with atrial fibrillation at risk for stroke, treatment with asundexian at a dose of 50 mg once daily was associated with a higher incidence of stroke or systemic embolism than treatment with apixaban in the period before the trial was stopped prematurely. There were fewer major bleeding events with asundexian than with apixaban during this time. (Funded by Bayer; OCEANIC-AF ClinicalTrials.gov number, NCT05643573; EudraCT number, 2022-000758-28.).

Prehospital Activation of the Cardiac Catheterization Laboratory in ST-Segment-Elevation Myocardial Infarction for Primary Percutaneous Coronary Intervention.

Background Prehospital activation of the cardiac catheter laboratory is associated with significant improvements in ST-segment-elevation myocardial infarction (STEMI) performance measures. However, there are equivocal data, particularly within Australia, regarding its influence on mortality. We assessed the association of prehospital activation on performance measures and mortality in patients with STEMI treated with primary percutaneous coronary intervention from the Queensland Cardiac Outcomes Registry (QCOR). Methods and Results Consecutive ambulance-transported patients with STEMI treated with primary percutaneous coronary intervention were analyzed from January 1, 2017 to December 31, 2020 from the QCOR. The total and direct effects of prehospital activation on the primary outcomes (30-day and 1-year cardiovascular mortality) were estimated using logistic regression analyses. Secondary outcomes were STEMI performance measures. Among 2498 patients (mean age: 62.2±12.4 years; 79.2% male), 73% underwent prehospital activation. Median door-to-balloon time (34 minutes [26-46] versus 86 minutes [68-113]; P<0.001), first-electrocardiograph-to-balloon time (83.5 minutes [72-98] versus 109 minutes [81-139]; P<0.001), and proportion of patients meeting STEMI targets (door-to-balloon <60 minutes 90% versus 16%; P<0.001), electrocardiograph-to-balloon time <90 minutes (62% versus 33%; P<0.001) were significantly improved with prehospital activation. Prehospital activation was associated with significantly lower 30-day (1.6% versus 6.6%; P<0.001) and 1-year cardiovascular mortality (2.9% versus 9.5%; P<0.001). After adjustment, no prehospital activation was strongly associated with increased 30-day (odds ratio [OR], 3.6 [95% CI, 2.2-6.0], P<0.001) and 1-year cardiovascular mortality (OR, 3.0 [95% CI, 2.0-4.6]; P<0.001). Conclusions Prehospital activation of cardiac catheterization laboratory for primary percutaneous coronary intervention was associated with significantly shorter time to reperfusion, achievement of STEMI performance measures, and lower 30-day and 1-year cardiovascular mortality.

Oral Anticoagulant Use in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Review of the Evidence With Recommendations for Australian Clinical Practice.

Chronic kidney disease is common in patients with atrial fibrillation (AF) and is associated with heightened risks of stroke/systemic embolisation and bleeding. In this review we outline the evidence for AF stroke prevention in kidney disease, identify current knowledge gaps, and give recommendations for anticoagulation at various stages of chronic kidney disease. Overall, anticoagulation is underused. Warfarin use becomes increasingly difficult with advancing kidney disease, with difficulty maintaining international normalised ratio (INR) in therapeutic range, increased risk of intracranial and fatal bleeding compared to non-vitamin K oral anticoagulants (NOACs), and high rates of discontinuation. Similarly, the direct thrombin inhibitor dabigatran is not recommended as it is predominantly renally excreted with consequent increased plasma levels and bleeding risk with advanced kidney disease. The Factor Xa inhibitors apixaban and rivaroxaban have less renal excretion (25-35%), modest increases in plasma levels with advancing kidney disease, and are the preferred first line choice for anticoagulation in moderate kidney disease based on strong evidence from randomised clinical trials (RCTs). In severe kidney disease there is a paucity of RCT data, but extrapolation of the pharmacokinetic and RCT data for moderate kidney disease, and observational studies, support the considered use of dose-adjusted Factor Xa inhibitors unless the bleeding risk is prohibitive. In Australia, apixaban is approved for creatinine clearance down to 25 mL/min, and rivaroxaban down to 15 mL/min. For end-stage kidney disease warfarin is the only agent approved, but we recommend against anticoagulation (except in selected cases) due to high bleeding risk, multiple co-morbidities, and questionable benefit.

Balancing the Risks of Recurrent Ischaemic and Bleeding Events in a Stable Post ACS Population.

OBJECTIVE: To better guide decisions regarding antithrombotic treatment in individual patients surviving 6 months following an acute coronary syndrome (ACS) by balancing between subsequent recurrent ischaemic and bleeding risk. METHODS: Patients surviving 6 months following an ACS were followed in an Australian registry. Ischaemic (composite of cardiovascular death, myocardial infarction or stroke) and bleeding (≥BARC 2) events were collected. A dual binary outcome modelling strategy was used arriving at a common set of variables from which bleeding and ischaemic risk could be independently determined in individual patients. Patients in whom bleeding rates exceeded composite ischaemic event rates during the follow-up period were identified. RESULTS: The cohort comprised 5,905 patients in whom 215 experienced an ischaemic event and 49 a bleeding event. The single set of variables included in both ischaemic and bleeding models (C-statistics 0.71 and 0.72 respectively) included modified TIGRIS1 ischaemic score, mode of revascularisation, history of heart failure, anaemia, multivessel disease, readmission within 6 months of index ACS and age >75. In the majority, ischaemic events were more frequent than bleeding events. In higher risk patients post coronary artery bypass grafting (CABG), bleeding events were more frequent than recurrent ischaemic events. CONCLUSION: The risk of recurrent ischaemic events exceeds bleeding in most patients followed 6 to 24 months following an ACS. Post CABG patients with comorbidities have a higher risk of bleeding over this period during which time attention should be directed towards modifiable bleeding risk factors including requirement for dual antiplatelet therapy.

Composite Echocardiographic Score to Predict Long-Term Survival Following Myocardial Infarction.

BACKGROUND: Whilst the left ventricular ejection fraction (LVEF) remains the primary echocardiographic measure widely utilised for risk stratification following myocardial infarction (MI), it has a number of well recognised limitations. The aim of this study was to compare the prognostic utility of a composite echocardiographic score (EchoScore) composed of prognostically validated measures of left-ventricular (LV) size, geometry and function, to the utility of LVEF alone, for predicting survival following MI. METHODS: Retrospective data on 394 consecutive patients with a first-ever MI were included. Comprehensive echocardiography was performed within 24 hours of admission for all patients. EchoScore consisted of LVEF<50%, left atrial volume index>34 mL/m2, average E/e >14, E/A ratio>2, abnormal LV mass index, and abnormal LV end-systolic volume index. A single point was allocated for each measure to derive a score out of 6. The primary outcome measure was all-cause mortality. RESULTS: At a median follow-up of 24 months there were 33 deaths. On Kaplan-Meier analysis, a high EchoScore (>3) displayed significant association with all-cause mortality (log-rank χ2=74.48 p<0.001), and was a better predictor than LVEF<35% (log-rank χ2=17.01 p<0.001). On Cox proportional-hazards multivariate analysis incorporating significant clinical and echocardiographic predictors, a high EchoScore was the strongest independent predictor of all-cause mortality (HR 6.44 95%CI 2.94-14.01 p<0.001), and the addition of EchoScore resulted in greater increment in model power compared to addition of LVEF (model χ2 56.29 vs 44.71 p<0.001, Harrell's C values 0.83 vs 0.79). CONCLUSIONS: A composite echocardiographic score composed of prognostically validated measures of LV size, geometry, and function is superior to LVEF alone for predicting survival following MI.

Patients With Diabetes at High Bleeding Risk With 1-Month Dual Antiplatelet Therapy: Onyx ONE Clear Results.

Background: Patients with diabetes mellitus (DM) are at a higher risk of ischemic events compared with patients without DM. Percutaneous coronary intervention (PCI) with the Resolute Onyx zotarolimus-eluting stent (ZES) followed by 1-month dual antiplatelet therapy (DAPT) is safe and effective in patients with high bleeding risk. However, outcomes in patients with DM are not fully understood. Methods: Onyx ONE Clear was a prospective, multicenter study that included patients receiving the Resolute Onyx ZES during PCI and 1-month DAPT. The primary end point was a composite of cardiac death (CD) or myocardial infarction from 1 month to 12 months. Results: Among the Onyx ONE Clear population (N = 1506), 39% had DM. Patients with DM had a higher incidence of hypertension, hyperlipidemia, and previous PCI and a higher body mass index than patients without DM. Patients with diabetes were also younger, more likely to be anemic, and experience renal failure. After adjusting for baseline differences between the groups, the Kaplan-Meier rates of CD or myocardial infarction (9.3% vs 6.1%; P = .122, unadjusted P = .010) and target lesion failure (10.2% vs 7.7%; P = .294, unadjusted P = .056) between 1 month and 12 months were not significantly different in patients with and without DM. The rates of target lesion revascularization were also similar in both groups, and stent thrombosis was very low and comparable in both arms after adjusting for baseline differences. Non-CD and bleeding were more frequent in patients with DM. Conclusions: Patients with diabetes treated with the Resolute Onyx ZES followed by 1-month DAPT had favorable 12-month ischemic outcomes after accounting for baseline differences between patients with and without DM, supporting the safety and efficacy of the treatment in selected patients with DM at high bleeding risk.

Direct Oral Anticoagulants in Asian Patients with Atrial Fibrillation: Consensus Recommendations by the Asian Pacific Society of Cardiology on Strategies for Thrombotic and Bleeding Risk Management.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

Determinants of Diastolic Dysfunction Following Myocardial Infarction: Evidence for Causation Beyond Infarct Size.

BACKGROUND: The determinants of severe diastolic dysfunction (DD) following myocardial infarction (MI) are not well defined. This study sought to define the determinants of severe DD (restrictive mitral inflow pattern on Doppler echocardiography [RFP]) in patients with a first-ever MI, with particular emphasis on the impact of infarct size. METHODS: Retrospective single-centre study including consecutive patients admitted to a tertiary referral centre with a first-ever non-ST-elevation-MI (NSTEMI) or ST-elevation-MI (STEMI) (n=477). Peak troponin-I (Peak-TnI) was used as the principal measure of infarct size, whilst left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were regarded as surrogate measures. Echocardiography was performed within 24 hours of admission for all patients. RFP was defined as E/A ratio >2.0 or E/A ratio >1.5 and E-wave deceleration time <140 ms. RESULTS: A total of 69 patients (14.5%) had RFP. Peak-TnI levels were higher in the RFP group (32.6±32.7 versus 16.9±25.2 µg/L, p<0.001). In sequential multivariable models incorporating significant clinical, angiographic and left ventricular (LV) size-related variables, Peak-TnI (OR 1.98, p=0.001), WMSI (OR 2.34, p=0.048) and LVEF (OR 0.97, p=0.044) were independent predictors of RFP. Presence of diabetes was also an independent predictor in all the models constructed. When patients were stratified according to an LVEF of 50%, 39% of RFP patients had a preserved LVEF (RFP/preserved EF group), and these patients had lower Peak-TnI levels compared to the RFP/reduced EF group (14.4±18.7 vs 44.5±35.5 µg/L). CONCLUSIONS: Whilst infarct size is a major determinant of severe diastolic dysfunction after MI, a significant subset of patients develop severe diastolic dysfunction despite a small infarct size and preserved LVEF, highlighting that other factors such as pre-existing diastolic dysfunction due to risk factors such as diabetes have an important role in causation.

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial.

BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. METHODS: 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. RESULTS: Compared with no GPI (n = 930), routine GPI (n = 525) or bailout GPI (n = 175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p = 0.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p = 0.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p = 0.92). CONCLUSION: Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation.

Revascularization Strategies in Patients With STEMI: Culprit-Only vs Multivessel Revascularization Using Percutaneous Coronary Intervention.

BACKGROUND: Approximately 50% of patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) have multivessel coronary disease (MVD). Evidence on the best PCI approach for these patients is conflicting. The aim of this study is to examine Australian data from the CONCORDANCE registry to describe the practice and outcomes of patients receiving multivessel vs culprit-only PCI. METHODS: Two cohorts were constructed from MVD-STEMI patients undergoing primary PCI at 41 hospitals between 2009 and 2015: culprit-only PCI (n = 587; 87%) and multivessel PCI (n = 82; 12%). Clinical characteristics were described, and the outcomes were all-cause mortality, heart failure, and myocardial reinfarction, in-hospital and at 6-month follow-up. The relative prevalence of each procedure over time was also described. RESULTS: The patient cohorts were comparable in age, sex, and cardiovascular risk factors. Patients with higher Killip scores were more likely to receive multivessel PCI (P=.02). The multivessel group was significantly more likely to have in-hospital cardiogenic shock (P<.01), myocardial reinfarction (P=.02), cardiac arrest (P=.02), and stroke (P=.01). There was no difference in the incidence of ischemic events at 6 months, but the multivessel group had a lower rate of planned repeat revascularizations (12% vs 2%; P=.03). There was no difference in the relative frequency of multivessel vs culprit-only PCI during the observation period. CONCLUSIONS: The relative frequency of multivessel vs culprit-only PCI has not changed from 2009-2015. Index complete revascularization for STEMI-MVD patients is more likely to be performed in those with worse presentations and is associated with worse in-hospital complications.

Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention: A subanalysis of the ATLANTIC Trial.

BACKGROUND: In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system. METHODS: This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution. RESULTS: Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06). CONCLUSIONS: This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.

Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: ATLANTIC-Morphine.

BACKGROUND: Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management. METHODS: ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded. RESULTS: Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02). CONCLUSIONS: Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain. TRIAL REGISTRATION: 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 (≥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.

Preventing recurrent events in survivors of acute coronary syndromes in Australia: consensus recommendations using the Delphi process.

OBJECTIVE: There remain substantial gaps in implementation of evidence-based care in patients with acute coronary syndromes (ACS) in Australia, which contribute to high recurrent event rates. Improved translation of evidence into effective action is a key health-care priority. We engaged cardiovascular experts from across Australia to develop straightforward, easily actionable recommendations on key medications to use following ACS. METHODS: An eight-person steering committee (SC) reviewed the published evidence and developed an initial set of statements to be developed into consensus recommendations using a modified Delphi technique. A panel of 21 expert cardiologists in the ACS field (including the SC) voted on their level of agreement with the statements using a 6 point Likert scale. Statements that did not reach consensus (≥80% agreement) were reviewed by the SC, modified as appropriate based on input from the panel and circulated for re-voting. RESULTS: Twenty-eight statements were developed by the SC across six classes of medication: low-density lipoprotein (LDL) cholesterol lowering agents, aspirin, dual antiplatelet therapy, renin-angiotensin-aldosterone system inhibitors, beta blockers and "other". Twenty-six recommendations were endorsed by the voting panel; two statements did not reach consensus. CONCLUSIONS: Despite the extensive evidence base and detailed guidelines outlining best practice post ACS, there remain considerable gaps in translating these into everyday care. We used an internationally recognized technique to develop practical consensus recommendations on medical treatment following ACS. These simple, up-to-date recommendations aim to improve evidence-based medication use and thereby reduce the risk of future cardiovascular events for Australian patients with ACS.

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).

Validating the Manchester Acute Coronary Syndromes (MACS) and Troponin-only Manchester Acute Coronary Syndromes (T-MACS) rules for the prediction of acute myocardial infarction in patients presenting to the emergency department with chest pain.

BACKGROUND: The Manchester Acute Coronary Syndromes (MACS) rule and the Troponin-only MACS (T-MACS) rule risk stratify patients with suspected acute coronary syndrome (ACS). This observational study sought to validate and compare the MACS and T-MACS rules for assessment of acute myocardial infarction (AMI). METHODS: Prospectively collected data from twoEDs in Australia and New Zealand were analysed. Patients were assigned a probability of ACS based on the MACS and T-MACS rules, incorporating high-sensitivity troponin T, heart-type fatty acid-binding protein, ECG results and clinical symptoms. Patients were then deemed very low risk, low risk, intermediate or high risk if their MACS probability was less than 2%, between 2% and 5%, between 5% and 95% and greater than 95%, respectively. The primary endpoint was 30-day diagnosis of AMI. The secondary endpoint was 30-day major adverse cardiac event (MACE) including AMI, revascularisation or coronary stenosis (>70%). Sensitivity, specificity and predictive values were calculated to assess the accuracy of the MACS and T-MACS rules. RESULTS: Of the 1244 patients, 114 (9.2%) were diagnosed with AMI and 163 (13.1%) with MACE. The MACS and T-MACS rules categorised 133 (10.7%) and 246 (19.8%) patients, respectively, as very low risk and potentially suitable for early discharge from the ED. There was one false negative case for both rules making sensitivity 99.1% (95.2%-100%). CONCLUSIONS: MACS and T-MACS accurately risk stratify very low risk patients. The T-MACS rule would allow for more patients to be discharged early. The potential for missed MACE events means that further outpatient testing for coronary artery disease may be required for patients identified as very low risk.

Differences in Presentation, Management and Outcomes in Women and Men Presenting to an Emergency Department With Possible Cardiac Chest Pain.

BACKGROUND: Research suggests that female patients with acute coronary syndrome (ACS) experience delays in emergency department (ED) management and are less likely to receive guideline-based treatments and referrals for follow-up testing. Women are often found to have poorer clinical outcomes in comparison to men. This study aimed to assess current sex differences in the presentation, management and outcomes of patients with undifferentiated chest pain presenting to a tertiary ED. METHODS: Data were analysed from two prospective studies conducted at a single Australian site between 2007 and 2014. Eligible patients were those of 18 years of age or older presenting with at least 5 minutes of chest pain or other symptoms for which the treating physician planned to investigate for possible ACS. Presenting symptoms, ED time measures, follow-up testing and outcomes, including 30-day ACS and mortality, were measured and compared between male and female patients. RESULTS: Of 2349 (60% men) patients presenting with chest pain, 153 men and 51 women were diagnosed with ACS within 30days . Presenting symptoms were similar in men and women with confirmed ACS. Time from symptom onset to ED presentation, time spent in the ED and total time in hospital were similar between the sexes. Male and female patients had similar rates of follow-up provocative testing. After adjustment for clinical factors, the odds of undergoing angiography were 1.8 (95% CI: 1.36-2.40) times higher for men than women. Of those undergoing coronary angiography within 30 days, a smaller proportion of women, compared to men, received revascularisation. Within 30 days, three (0.2%) male and one (0.1%) female patient died. CONCLUSION: Minimal sex differences were observed in the contemporary emergency management of patients presenting with suspected ACS. Thirty-day outcomes were similarly low in men and women despite lower rates of coronary angiography and revascularisation in women. Further research is required to replicate these results in different hospital systems and cultural settings.

Suspected ACS Patients Presenting With Myocardial Damage or a Type 2 Myocardial Infarction Have a Similar Late Mortality to Patients With a Type 1 Myocardial Infarction: A Report From the Australian and New Zealand 2012 SNAPSHOT ACS Study.

BACKGROUND: Cardiac troponin (T and I) are considered the standard markers for detection of myocardial damage and the diagnosis of acute coronary syndrome (ACS) among patients who present to an emergency department with chest pain. However, these markers can be released in other situations and may be associated with short- and long-term clinical outcomes. In this study, we examine late mortality rates among patients presenting with a suspected ACS due to an unstable coronary plaque and those patients having a non-ACS. METHODS: 4388 patients were hospitalised with suspected ACS, between 14 and 27 May 2012 in the Australia and New Zealand SNAPSHOT ACS study. Those patients were categorised in five diagnostic groups: 1) ST elevation MI (n=419); 2) non-ST elevation MI (n=1012); 3) unstable angina (n=925); 4) non-ACS diagnoses (n=837); and 5) chest pain considered unlikely ischaemic (not otherwise specified, n=1195). RESULT: The respective mortality rates at 18 months in these groups were 16.2%, 16.3%, 6.8%, 12.8%, and 4.8%; Pearson χ2=110 p<0.001. Among non-ACS diagnoses patients (group 4) those with the highest mortality rates (cardiac (14.4%), respiratory (18.2%), sepsis (15.4%) and neoplastic (67%) diagnoses) had the highest rates of elevated troponin levels (48%, 31%, 38% and 67% respectively). By contrast, those with the lowest mortality rates (musculoskeletal (2.9%), gastrointestinal disorders (3.9%) and non-specific chest pain (7.4%)) had the lowest rate of elevated troponin levels (9%, 18% and 15.8% respectively). However, after adjusting for baseline clinical and demographic characteristics, the mortality rate at 18 months for patients with elevated troponin was similar for ACS or non-ACS diagnoses (Hazard Ratio, 95% C.I.0.98-1.07, p=0.333). CONCLUSIONS: Among patients in the 2012 SNAPSHOT ACS study, non-ACS diagnoses characterised by high rates of elevated troponin levels had high mortality rates similar to those diagnosed with ACS. Therapies known to be effective in ACS patients, including early invasive management, should be examined in these non-ACS patients with troponin elevations within adequately powered randomised trials.