Corrigendum to 'National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016' Heart Lung and Circulation volume 25, (2016) 898 - 952.

Please note that on p.929 in 5.2.2.7, paragraph 3, the dose of dabigatran should read as BD rather than daily. We regret any inconvenience that this may have caused.

Impact of a regionalised clinical cardiac support network on mortality among rural patients with myocardial infarction.

OBJECTIVE: To evaluate the impact of the regionalised Integrated Cardiovascular Clinical Network (ICCNet) on 30-day mortality among patients with myocardial infarction (MI) in an Australian rural setting. DESIGN, SETTING AND PATIENTS: An integrated cardiac support network incorporating standardised risk stratification, point-of-care troponin testing and cardiologist-supported decision making was progressively implemented in non-metropolitan areas of South Australia from 2001 to 2008. Hospital administrative data and statewide death records from 1 July 2001 to 30 June 2010 were used to evaluate outcomes for patients diagnosed with MI in rural and metropolitan hospitals. MAIN OUTCOME MEASURE: Risk-adjusted 30-day mortality. RESULTS: 29 623 independent contiguous episodes of MI were identified. The mean predicted 30-day mortality was lower among rural patients compared with metropolitan patients, while actual mortality rates were higher (30-day mortality: rural, 705/5630 [12.52%] v metropolitan, 2140/23 993 [8.92%]; adjusted odds ratio [OR], 1.46; 95% CI, 1.33-1.60; P< 0.001). After adjustment for temporal improvement in MI outcome, availability of immediate cardiac support was associated with a 22% relative odds reduction in 30-day mortality (OR, 0.78; 95% CI, 0.65-0.93; P= 0.007). A strong association between network support and transfer of patients to metropolitan hospitals was observed (before ICCNet, 1102/2419 [45.56%] v after ICCNet, 2100/3211 [65.4%]; P< 0.001), with lower mortality observed among transferred patients. CONCLUSION: Cardiologist-supported remote risk stratification, management and facilitated access to tertiary hospital-based early invasive management are associated with an improvement in 30-day mortality for patients who initially present to rural hospitals and are diagnosed with MI. These interventions closed the gap in mortality between rural and metropolitan patients in South Australia.

The prognostic meaning of the full spectrum of aVR ST-segment changes in acute myocardial infarction.

AIMS: ST-elevation in lead aVR is known to be associated with a worse prognosis in patients with acute ST elevation myocardial infarction (MI) but the significance of ST depression in lead aVR has been unclear. Infarction of the inferior apex of the left ventricle may not be appreciated on the standard 12-lead electrocardiogram (ECG) except by observing ST depression in lead aVR which is reciprocal to lead V(7). We therefore determined the prognostic value of the full spectrum of aVR ST changes in patients presenting with acute ST elevation MI. METHODS AND RESULTS: Lead aVR ST level was measured on randomization and 60 min ECGs in 15 315 patients with normal conduction from the HERO-2 trial. The outcome measure was 30-day mortality. aVR ST elevation ≥1 mm was associated with higher 30-day mortality for both inferior (22.5% for ≥1.5 mm and 13.2% for 1 mm) and anterior (23.5% for ≥1.5 mm and 11.5% for 1 mm) infarction. In contrast, deeper aVR ST depression (0, 0.5, 1, and ≥1.5 mm) was associated with higher mortality for anterior infarction (9.8, 13.2, 12.8, and 16.8%, respectively, trend P-value <0.0001) but not for inferior infarction. The resolution of aVR ST depression and ST elevation 60 min after fibrinolysis was associated with lower mortality. CONCLUSION: There is a U-shaped relationship between 30-day mortality and aVR ST level in patients presenting with anterior but not inferior ST elevation MI.

aVR ST elevation: an important but neglected sign in ST elevation acute myocardial infarction.

AIM: This study evaluated the prognostic implications of aVR ST elevation during ST elevation acute myocardial infarction (AMI). METHODS AND RESULTS: The Hirulog and Early Reperfusion/Occlusion-2 study randomized 17 073 patients with acute ST elevation AMI within 6 h of symptom onset to receive either bivalirudin or heparin, in addition to streptokinase and aspirin. The treatments had no effect on the primary endpoint of 30-day mortality. Electrocardiographic recordings were performed at randomization and at 60 min after commencing streptokinase. aVR ST elevation > or =1 mm was associated with higher 30-day mortality in 15 315 patients with normal intraventricular conduction regardless of AMI location (14.7% vs. 11.2% for anterior AMI, P = 0.0045 and 16.0% vs. 6.4% for inferior AMI, P < 0.0001). After adjusting for summed ST elevation and ST depression in other leads, associations with higher mortality were found with aVR ST elevation of > or =1.5 mm for anterior [odds ratio 1.69 (95% CI 1.16 to 2.45)] and of > or =1 mm for inferior AMI [odds ratio 2.41 (95% CI 1.76 to 3.30)]. There was a significant interaction between aVR ST elevation and infarct location. Thirty-day mortality was similar with anterior and inferior AMI when aVR ST elevation was present (11.5% vs. 13.2%, respectively, P = 0.51 with 1 mm and 23.5% vs. 22.5% respectively, P = 0.84 with > or = 1.5 mm ST elevation). After fibrinolytic therapy, resolution of ST elevation in aVR to <1 mm was associated with lower mortality, while new ST elevation > or =1 mm was associated with higher mortality. CONCLUSION: aVR ST elevation is an important adverse prognostic sign in AMI.

Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention.

BACKGROUND: Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI. METHODS: In this prospective, open-label, multicenter, randomized trial, we randomly assigned 3528 patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionated heparin adjusted for activated clotting time, stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors. The primary end point was the incidence of major or minor bleeding that was not related to coronary-artery bypass grafting. The main secondary end point was the percentage of patients in whom the target anticoagulation levels were reached. RESULTS: Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non-CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI, -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced in both enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001). CONCLUSIONS: In elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844 [ClinicalTrials.gov].).

Risk stratification of patients with acute anterior myocardial infarction and right bundle-branch block: importance of QRS duration and early ST-segment resolution after fibrinolytic therapy.

BACKGROUND: Patients with an acute anterior ST-segment elevation myocardial infarction and right bundle-branch block (RBBB) have a high mortality risk, which may be stratified by early ECG changes. METHODS AND RESULTS: In the Hirulog Early Reperfusion Occlusion (HERO-2) trial, 17 073 patients with acute myocardial infarction (AMI) within 6 hours of symptom onset were treated with streptokinase and randomized to receive bivalirudin or heparin. There was no difference in the primary end point of 30-day mortality. ECGs were recorded at randomization and 60 minutes after fibrinolytic therapy was begun. The 30-day mortality rate was 31.6% in the 415 patients with RBBB and anterior AMI at randomization and 33% in the 100 patients who developed new RBBB at 60 minutes from normal baseline conduction accompanying an anterior AMI. An increase in QRS duration by 20-ms increments was associated with increasing 30-day mortality rate in both RBBB groups on multivariable analyses with covariates of age, Killip class, systolic blood pressure, pulse, and prior infarction. Patients with QRS duration > or = 160 ms had higher 30-day mortality rate than those with QRS duration < 160 ms (37.2% versus 27.2%, P = 0.03, and 46.2% versus 24.5%, P = 0.025, in the 2 groups, respectively). For the patients with RBBB and anterior MI at randomization, RBBB resolved at 60 minutes in 40 patients, but 30-day mortality rate was unchanged. For those with persisting RBBB at 60 minutes, 30-day mortality rate was lower if ST-segment elevation had resolved by > or = 50% (20.4% versus 35.3%, P = 0.006). CONCLUSIONS: In patients with anterior AMI and RBBB, increasing QRS duration is associated with increasing 30-day mortality. Early ST-segment resolution after fibrinolytic therapy despite persisting RBBB is associated with lower mortality rate.

Comparison of percutaneous coronary intervention and coronary artery bypass grafting after acute myocardial infarction complicated by cardiogenic shock: results from the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial.

BACKGROUND: The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated the survival advantage of emergency revascularization versus initial medical stabilization in patients developing cardiogenic shock after acute myocardial infarction. The relative merits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with shock have not been defined. The objective of this analysis was to compare the effects of PCI and CABG on 30-day and 1-year survival in the SHOCK trial. METHODS AND RESULTS: Of the 302 trial patients, 128 with predominant left ventricular failure had emergency revascularization. The selection of revascularization procedures was individualized. Eighty-one patients (63.3%) had PCI, and 47 (36.7%) had CABG. The median time from randomization to intervention was 0.9 hours (interquartile range [IQR], 0.3 to 2.2 hours) for PCI and 2.7 hours (IQR, 1.3 to 5.5 hours) for CABG. Baseline demographics and hemodynamics were similar, except that there were more diabetics (48.9% versus 26.9%; P=0.02), 3-vessel disease (80.4% versus 60.3%; P=0.03), and left main coronary disease (41.3% versus 13.0%; P=0.001) in the CABG group. In the PCI group, 12.3% had 2-vessel and 2.5% had 3-vessel interventions. In the CABG group, 84.8% received > or =2 grafts, 52.2% received > or =3 grafts, and 87.2% were deemed completely revascularized. The survival rates were 55.6% in the PCI group compared with 57.4% in the CABG group at 30 days (P=0.86) and 51.9% compared with 46.8%, respectively, at 1 year (P=0.71). CONCLUSIONS: Among SHOCK trial patients randomized to emergency revascularization, those treated with CABG had a greater prevalence of diabetes and worse coronary disease than those treated with PCI. However, survival rates were similar. Emergency CABG is an important component of an optimal treatment strategy in patients with cardiogenic shock, and should be considered a complementary treatment option in patients with extensive coronary disease.

Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: The elderly constitute an increasing proportion of acute myocardial infarction patients and have disproportionately high mortality and morbidity. Those with heart failure or impaired left ventricular left ventricular function after acute myocardial infarction have high complication and mortality rates. Little is known about outcomes with contemporary therapies in these patients. METHODS AND RESULTS: The Valsartan in Acute Myocardial Infarction Trial (VALIANT) randomized 14,703 patients with heart failure and/or left ventricular ejection fraction <40% to receive captopril, valsartan, or both. Mortality and a composite end point, including cardiovascular mortality, readmission for heart failure, reinfarction, stroke, and resuscitated cardiac arrest, were compared for the age groups of <65 (n=6988), 65 to 74 (n=4555), 75 to 84 (n=2777), and > or =85 (n=383) years. With increasing age, 3-year mortality almost quadrupled (13.4%, 26.3%, 36.0%, and 52.1%, respectively), composite end-point events more than doubled (25.2%, 41.0%, 52.3%, and 66.8%), and hospital admissions for heart failure almost tripled (12.0%, 23.1%, 31.3%, and 35.4%). Outcomes did not differ between the 3 study treatments in any age group. Adverse events associated with captopril and valsartan were more common in the elderly and in patients receiving combination therapy. With increasing age, use of aspirin, beta-blockers, and statins declined, and use of digoxin, calcium-channel blockers, and non-potassium-sparing diuretics increased. On 3-year multivariable analysis, each 10-year age increase was associated with a hazard ratio of 1.49 (95% CI, 1.426 to 1.557; P<0.0001) for mortality and an odds ratio of 1.38 (95% CI, 1.31 to 1.46; P<0.0001) for readmission with heart failure. CONCLUSIONS: Outcomes remained poor in elderly patients with heart failure and/or impaired left ventricular systolic function after acute myocardial infarction, although most received beta-blockers and all received an ACE inhibitor and/or an angiotensin receptor blocker. Better therapies and increased use of aspirin, beta-blockers, and statins are needed in this important and increasing patient group.

Patients with prolonged ischemic chest pain and presumed-new left bundle branch block have heterogeneous outcomes depending on the presence of ST-segment changes.

OBJECTIVES: The purpose of this research was to examine the prognostic value of ST-segment changes (concordant ST-segment elevation and/or precordial V1 to V3 ST-segment depression) during presumed-new left bundle branch block (LBBB) in patients receiving fibrinolytic therapy. BACKGROUND: These patients are often considered high-risk, but their outcome is not well-defined. METHODS: The Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial compared bivalirudin with heparin in patients receiving streptokinase for ST-segment elevation or presumed-new LBBB. Each patient with LBBB was matched with a control (with normal intraventricular conduction) for age, gender, pulse rate, systolic blood pressure, Killip class, and region. RESULTS: A total of 300 patients had LBBB (92 with and 208 without ST-segment changes) and 15,340 had normal conduction. Acute myocardial infarction (AMI) occurred in 80.7% of LBBB patients and 88.7% of controls (p = 0.006). ST-segment changes were specific (96.6%) but not sensitive (37.8%) for enzymatic diagnosis of AMI. Mortality at 30 days was similar in LBBB patients with ST-segment changes (21.7%) and controls (25.0%, p = 0.563), but lower in LBBB patients without ST-segment changes than in controls (13.5% vs. 21.6%, p = 0.022). In the whole HERO-2 cohort, the LBBB patients with ST-segment changes had higher mortality than patients with normal conduction (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.78 to 2.42). The LBBB patients without ST-segment changes had lower mortality than patients with normal conduction (OR 0.52, 95% CI 0.33 to 0.80). CONCLUSIONS: ST-segment changes during LBBB are specific for the diagnosis of AMI and predict 30-day mortality; LBBB patients without ST-segment changes have lower adjusted 30-day mortality than those with normal conduction. Trials are required to determine the best treatment for high-risk and low-risk patients with LBBB.

Efficacy and safety of enoxaparin compared with unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial.

BACKGROUND: Enoxaparin reduces ischemic events more effectively than unfractionated heparin (UFH) in patients treated conservatively for non-ST-segment elevation acute coronary syndrome. The SYNERGY trial compared these agents in high-risk patients undergoing early invasive treatment. Enoxaparin was noninferior to UFH for the 30-day primary end point of death/myocardial infarction (MI), but modestly increased bleeding. METHODS AND RESULTS: This article compares the outcomes of the 4687 SYNERGY patients (47%) undergoing percutaneous coronary intervention, who were randomized to receive enoxaparin or UFH. Antithrombotic therapy was administered prerandomization in 78%. Crossover (usually in the catheterization laboratory) to the alternative antithrombotic occurred in 14.6% of enoxaparin patients and 2.9% of UFH-treated patients (P < .0001). Stenting was performed in 86.3%. Abrupt vessel closure occurred in 1.3% of enoxaparin patients and 1.7% of UFH-treated patients (P = .318). The rates of death/MI were similar at 30 days (13.1% with enoxaparin vs 14.2% with UFH, P = .289). GUSTO severe bleeding occurred with similar frequency in both groups (1.5% vs 1.6%, P = .688). TIMI major bleeding was more common with enoxaparin (3.7% vs 2.5% with UFH, P = .028). Transfusions were more frequent with enoxaparin than with UFH (6.8% vs 5.4%, P = .047). TIMI major bleeding increased with crossover from enoxaparin to UFH (from 3.7% to 7.8%) and from UFH to enoxaparin (from 2.5% to 8.6%). Statistical adjustment to model reasons for crossover did not affect the overall safety and efficacy outcomes. CONCLUSIONS: In high-risk patients undergoing early percutaneous coronary intervention for acute coronary syndrome, enoxaparin avoids the need for monitoring and achieves similar effectiveness to UFH but is associated with more bleeding.

Baseline Q-wave surpasses time from symptom onset as a prognostic marker in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

OBJECTIVES: We assessed the incremental value of baseline Q waves over time from symptom onset as a marker of clinical outcome in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Time from symptom onset is a central focus in STEMI patients. The presence of Q waves on the baseline electrocardiogram (ECG) has been suggested to be of incremental value to time from symptom onset in evaluating clinical outcomes. METHODS: We evaluated baseline Q waves and ST-segment resolution 30 min after primary percutaneous intervention (PCI) ECGs in 4,530 STEMI patients without prior infarction. Additionally, peak biomarkers; 90-day mortality; and the composite of death, congestive heart failure (CHF), or cardiogenic shock were assessed. RESULTS: Fifty-six percent of patients had baseline Q waves: they were older, more frequently male and diabetic, and had a more advanced Killip class. Patients with baseline Q waves had greater mortality and a higher composite rate of death, CHF, and shock versus patients without baseline Q waves at 90 days (5.3% vs. 2.1% and 12.1% vs. 4.8%, respectively, both p < 0.001). Complete ST-segment resolution was highest, whereas 90-day mortality and the composite outcome were lowest among those randomized < or =3 h without baseline Q waves. After multivariable adjustment, baseline Q-wave but not time from symptom onset was significantly associated with a 78% relative increase in the hazard of 90-day mortality and a 90% relative increase in the hazard of death, shock, and CHF. CONCLUSIONS: Baseline Q waves in STEMI patients treated with primary PCI provide an independent prognostic marker of clinical outcome. These data might be useful in designing future clinical trials as well as in evaluating patients for triage and potential transfer for planned primary PCI. (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction [APEX-AMI]; NCT00091637).

Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention 1-year results from the STEEPLE (SafeTy and efficacy of enoxaparin in percutaneous coronary intervention patients, an international randomized evaluation) trial.

OBJECTIVES: Our purpose was to evaluate long-term mortality and identify factors associated with 1-year mortality in patients who underwent elective percutaneous coronary intervention (PCI). BACKGROUND: While long-term outcomes in PCI patients have been reported previously, limited data are currently available regarding the comparative long-term outcomes in PCI patients who receive enoxaparin versus intravenous unfractionated heparin (UFH). METHODS: We conducted a follow-up analysis of clinical outcomes at 1 year in patients enrolled in the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation) trial of 3,528 patients undergoing elective PCI. Patients were randomized to receive either intravenous 0.50-mg/kg or 0.75-mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure. RESULTS: Mortality rates were 1.4%, 2.0%, and 1.5% from 1 month to 1 year, and 2.3%, 2.2%, and 1.9% from randomization to 1 year, after index PCI in patients receiving 0.50 mg/kg enoxaparin, 0.75 mg/kg enoxaparin, and UFH, respectively. Multivariate analysis identified nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio: 3.5, 95% confidence interval: 1.7 to 7.3; p < 0.001), and major bleeding within 48 h (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.5; p = 0.04) as the strongest independent risk factors for 1-year mortality. CONCLUSIONS: The 1-year mortality rates were low and comparable between patients receiving enoxaparin and UFH during elective PCI. Periprocedural ischemic or bleeding events were the strongest independent predictors of 1-year mortality. (The STEEPLE Trial; NCT00077844).

Impact of anticoagulation levels on outcomes in patients undergoing elective percutaneous coronary intervention: insights from the STEEPLE trial.

AIMS: To determine the relationship between anticoagulation levels during percutaneous coronary intervention, and ischaemic events and bleeding. METHODS AND RESULTS: A sub-analysis from the STEEPLE trial was conducted. Pre-defined target anticoagulation levels were achieved in 86% of patients receiving enoxaparin, compared with 20% receiving unfractionated heparin (UFH) (P < 0.001). A significant relationship was observed between anti-Xa levels > 0.9 IU/mL and covariate-adjusted rate of non-coronary artery bypass graft-related major and minor bleeding [odds ratio (OR) 1.6, 95% CI 1.0-2.5 for each unit of anti-Xa; P = 0.03]; anti-Xa levels and covariate-adjusted incidence of death, myocardial infarction, or revascularization showed no significance (P = 0.47). Major bleeding increased significantly with an activated clotting time (ACT) > 325 s (OR 1.6, 95% CI 1.1-2.2 per 100 s; P = 0.04). A significant relationship with increasing ischaemic events was observed when ACT was < 325 s (OR 0.7, 95% CI 0.2-0.8 per 100 s; P = 0.006) indicating a narrow therapeutic window. CONCLUSION: Target anticoagulation levels were achieved more readily in patients receiving enoxaparin. An anti-Xa level of up to 0.9 IU/mL has a good safety and efficacy profile; poor achievement of target ACT with UFH makes assessing the optimal range difficult.