Acute coronary syndrome and stable coronary artery disease: are they so different? Long-term outcomes in a contemporary PCI cohort.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are known to have poorer short-term prognosis compared to stable coronary artery (CAD) patients undergoing elective PCI. Few studies have made direct comparison of long-term mortality between ACS and stable CAD patients undergoing PCI. The aim of our study was to compare the long-term mortality following PCI between patients with ACS and those with stable CAD. METHODS: We examined consecutive patients undergoing PCI with stenting at a tertiary referral hospital. Clinical, angiographic and biochemical data were collected and analysed. The primary outcome was all-cause mortality retrieved from the Statewide Death Registry database. RESULTS: Included were 1923 consecutive PCI patients (970 stable CAD and 953 ACS). The mean follow-up time was 4.1 years ± 1.8 years. In-hospital mortality was 1.4% overall, seen exclusively in patients with ACS (n=28, 2.9%). Post-discharge mortality was 6.7% among patients with stable CAD and 10.5% for ACS (P<0.01). Multivariate predictors of post-discharge deaths for both groups included age (HR 1.08 per year, P<0.001) and impaired renal function (HR 2.49, P<0.001). Following adjustment for these factors, an ACS indication for PCI was not associated with greater post-discharge mortality (adjusted HR 1.18: 0.85-1.64, P=0.32). CONCLUSIONS: Patients undergoing PCI following an ACS have higher long-term mortality to those with stable CAD, which is potentially explained by a greater prevalence of comorbidities. This suggests that for the ACS population, contemporary interventional and medical management strategies may effectively and specifically counter the adverse prognostic impact of coronary instability and myocardial damage.

Clinical effectiveness in everyday practice: improving outcomes for all patients through a national acute coronary syndrome data collaborative.

The management of acute coronary syndromes (ACS) has an extensive and impressive evidence-base with which to guide clinical practice. Despite this, translation to the clinical environment has proved to be challenging and incomplete and can be attributed to patient, provider and system factors. Causes of suboptimal guideline adherence relate to diverse issues, including patient complexity, barriers in knowledge translation of guideline recommendations and a limited capacity within health services. Addressing these factors may enable more effective guideline implementation. In Australia, the infrastructure for clinical data management is fragmented, uncoordinated and often administratively driven, compromising access to important information, which might improve clinical effectiveness. An integrated approach is required to improve clinical effectiveness in ACS care in Australia. Greater access to information both to assist in clinical decision-making and monitoring outcomes may help direct the focus towards understudied populations and improve performance and clinically relevant outcomes. A peer-led initiative based on common datasets, providing rapid feedback, while developing and disseminating a 'toolbox' of proven and sustainable interventions, could improve clinical effectiveness in the Australian management of ACS and provides a rationale for a national ACS registry.

Unperceived treatment gaps in acute coronary syndromes.

BACKGROUND: Despite a strong evidence-base for several therapies recommended in the management of acute coronary syndromes (ACS), many patients do not receive these therapies. The barriers preventing translation of evidence into practice are incompletely understood. The aim of this study was to survey clinicians regarding barriers to implementing recommendations of recently published national clinical guidelines and to determine the extent to which these impact clinical practice. METHODS: A survey of clinicians at hospitals included in Australian Collaborative Acute Coronary Syndromes Prospective Audit (ACACIA, n = 3402, PML0051) was conducted, measuring self-stated knowledge, beliefs and guideline-concordant behaviours in relation to their care of ACS patients. Correlations between individual respondents' self-estimated rates and clinician's institutional rates of guideline-concordant behaviours were performed. RESULTS: Most respondents (n = 50/86, 58%) were aware of current guidelines and their scope, achieving 7/10 (Interquartile Range (IQR) = 2) median score on knowledge questions. Belief in benefits and agreement with guideline-recommended therapy was high. However, none of these factors correlated with increased use of guideline therapies. Apart from clopidogrel (r(s) = 0.28, p < 0.01) and early interventional therapy for high-risk non-ST elevation myocardial infarction (r(s) = 0.31, p < 0.01), there were no significant correlations between individual clinicians' self-estimated rates of guideline-concordant practice and rates recorded in ACACIA data for their respective institution. CONCLUSION: Beliefs about practice do not match actual practice. False beliefs regarding levels of evidence-based practice may contribute to inadequate implementation of evidence-based guidelines. Strategies such as continuous real-time audit and feedback of information for the delivery of care may help clinicians understand their levels of practice better and improve care.

Impact of acute and chronic risk factors on use of evidence-based treatments in patients in Australia with acute coronary syndromes.

OBJECTIVE: To determine whether acute risk factors (ARF) and chronic risk factors (CRF) contribute differently to the use of evidence-based treatments (EBT) for patients with acute coronary syndromes (ACS). DESIGN: Data were collected through a prospective audit of patients with ACS. Management was analysed by the presence of acute myocardial risk factors and chronic comorbid risk factors at presentation. SETTING: 39 hospitals across Australia. PATIENTS: 2599 adults presenting with ACS. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Use of EBT, in-hospital and 12-month death, recurrent myocardial infarction and bleeding. RESULTS: The number of ARF and CRF at presentation predicted in-hospital and 12-month death, recurrent myocardial infarction and bleeding. Patients with higher numbers of ARF were more likely to receive EBT (aspirin at presentation, 81.1% for zero ARF to 85.7% for > or =3 ARF, p<0.001; angiography 45.9% to 67.5%, p<0.001; reperfusion for ST elevation 50% to 70%, p = 0.392; beta blocker at discharge 66.5% to 74.4%, p<0.001). Patients with higher numbers of CRF were less likely to receive EBT (aspirin at presentation 90.4% for zero CRF to 68.8% for > or =4 CRF, p<0.001; angiography 78.8% to 24.7%, p<0.001; reperfusion for ST elevation 73.4% to 30%; p<0.001, beta blocker at discharge 75.2% to 55.6%; p<0.001). In multivariate regression analysis, ARF and CRF were the strongest predictors of receiving or failing to receive EBT, respectively. CONCLUSIONS: Patients presenting with many ARF are more likely to receive EBT, while patients presenting with many CRF are less likely to receive them. This has important implications for future quality-improvement efforts.

Polymorphonuclear leukocyte phagocytic function increases in plasminogen knockout mice.

BACKGROUND: Mice lacking plasminogen (PG-/-) require alternative pathways of fibrinolysis for survival. This may depend on polymorphonuclear leukocytes (PMN) that can clear soluble and insoluble fibrin(ogen) through PG-independent processes. Our objective was to demonstrate that PMNs from PG-/- mice exhibit increased Mac-1 dependent phagocytic activity, which may explain their increased fibrin(ogen)lytic activity compared with wild type (PG+/+) mice. METHODS: Phagocytic activity of PMNs from PG-/- and PG+/+ mice was compared following exposure to Staphylococcus aureus (S. aureus) particles and the expression of Mac-1 was assessed in parallel by flow cytometric analysis. Resistance to phorbol-12-myristate-13-acetate (PMA)-induced cell death was compared between PMNs from the different genotypes. RESULTS: Stimulation of PG-/- PMNs by opsonized S. aureus diluted in PG-/- plasma significantly increased phagocytosis (15-fold) compared with stimulation of PG+/+ PMNs in PG+/+ plasma. Incubation of PG-/- PMNs with PG+/+ plasma (control) or PG-/- plasma supplemented with human PG inhibited this increased phagocytic activity. Mac-1 cell surface density increased 6.2+/-1.0-fold in PG-/- PMNs versus 2.9+/-0.6-fold in PG+/+ PMNs (P < 0.01) indicating that Mac-1 may be associated with increased phagocytic activity. Supporting this, treatment of PG-/- PMNs with an anti-Mac-1 antibody in PG-/- plasma inhibited phagocytic activity. In addition, physiologic PG blocked Mac-1 accessibility at the surface of PMNs. Addition of PMA resulted in 33% death of PMNs from PG-/- mice versus 68% in PG+/+ controls (P < 0.001). CONCLUSIONS: PMNs from PG-/- mice exhibit a Mac-1 dependent increase in phagocytic activity that is suppressed with human PG, an anti-Mac-1 antibody or the plasma from PG+/+ mice. The propensity for PMNs from PG-/- mice to be activated in response to PMA together with their relative resistance to PMA-toxicity may contribute to increased PMN half-life and enhanced fibrin(ogen) clearance in the setting of PG deficiency.

Hierarchy of risk based on history and location of prior myocardial infarction in the thrombolytic era. GUSTO-I Investigators.

BACKGROUND: Among patients receiving thrombolytic therapy for myocardial infarction, the outcome for those with a history of infarction is dramatically worse than for those with their first event. Methods And Results We performed a post hoc analysis of patients with a history of myocardial infarction enrolled in the Global Utilization of Streptokinase and TPA for Occluded arteries (GUSTO)-I trial, focusing on the impact of the location of their current and prior events on mortality rates. Within the first 24 hours, mortality rate was greatest among patients with a current infarction in a territory remote from their previous event. By 48 hours after examination, mortality rates among patients with a second anterior infarct had overtaken that among patients with a current inferior/prior anterior infarct. This hierarchy of risk persisted at both 30 days and 1 year (mortality rate at 1 year: current anterior/prior inferior 23.2% +/- 1.4%, current anterior/prior anterior 20% +/- 1.5%, current inferior/prior anterior 17% +/- 1.2%, current inferior/prior inferior 10.8% +/- 0. 9%). CONCLUSIONS: In patients with ST-elevation myocardial infarction on a background of prior infarction, the location of current and prior events predicts a hierarchy of short- and long-term risk of death.

Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris.

After 2 weeks of nicorandil therapy, time to ischemia on stress testing was significantly less than on day 1 and not different from placebo. These data are consistent with attenuation of the anti-ischemic effects of this drug and suggest that the potassium channel-opening properties do not compensate for development of attenuation to the nitrate component of nicorandil.

Heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy and is being encountered more frequently in patients with cardiovascular disease as use of anticoagulant therapy becomes more widespread. Our understanding of the pathophysiology of this immune-mediated condition has improved in recent years, with heparin-platelet factor 4 complex as the culprit antigen in most patients. New sensitive laboratory assays for the pathogenic antibody are now available and should permit an earlier, more reliable diagnosis, but their optimal application remains to be defined. For patients in whom HIT is diagnosed, immediate discontinuation of heparin infusions and elimination of heparin from all flushes and ports are mandatory. Further management of patients with HIT is problematic at present, as there are no readily available alternative anticoagulant agents in the United States with proven efficacy in acute coronary disease. The direct thrombin inhibitors appear to be the most promising alternatives to heparin, when continued use of heparin is contraindicated, and the results of several multicenter trials evaluating their application in patients with HIT are awaited.

Benefit of early sustained reperfusion in patients with prior myocardial infarction (the GUSTO-I trial). Global Utilization of Streptokinase and TPA for occluded arteries.

The primary objective of this study was to characterize a large cohort of patients receiving thrombolytic therapy for acute myocardial infarction with respect to the group with a prior event. Patients were randomly assigned to 1 of 4 thrombolytic strategies. Baseline characteristics, 30-day outcomes, and 1-year mortality were compared between patients with (n = 6,704) and without (n = 34,143) prior myocardial infarction. Patients with prior myocardial infarction presented to the hospital earlier than those having their first event, but institution of thrombolytic therapy was delayed. Mortality at 30 days (11.7% vs 5.9%, p = 0.001) and 1 year (17.3% vs 8.2%, p < 0.001) was greater among patients with prior infarction, and independent of other demographic variables. Accelerated alteplase was more effective than streptokinase or combination therapy (30-day mortality 10.4% vs 12.2%, p = 0.012; 1-year mortality 15.9% vs 17.8%, p = 0.041). Infarct vessel patency did not differ between those with and without prior myocardial infarction (67.3% vs 67% at 90 minutes, p = 0.92); however, recurrent ischemia was more common in patients with prior myocardial infarction. Patients with healed myocardial infarction should be educated to ensure early hospital admission if they develop symptoms suggestive of acute infarction, and upon hospital arrival should be promptly triaged to receive reperfusion therapy with accelerated alteplase.