Life after abciximab; what's next for intracoronary thrombus?

A case is described in which the short-acting glycoprotein IIb/IIIa receptor antagonist tirofiban was used in combination with heparin, aspirin and prasugrel to successfully treat extensive intracoronary thrombus in a delayed presentation STEMI, illustrating the utility of this approach.

Glycosylated haemoglobin assessment in diabetic patients with acute coronary syndromes.

BACKGROUND: Guidelines for the management of acute coronary syndromes (ACS) advocate for maintaining adequate long-term glycaemic control in diabetic patients. Glycosylated haemoglobin (HbA1c) measurement is commonly used to monitor long-term glycaemic control in diabetes. AIMS: To evaluate the frequency and clinical predictors of in-hospital HbA1c measurement in diabetic patients presenting with ACS and the relationship between HbA1c assessment and mortality following discharge. METHODS: This registry-based cohort study included 1743 diabetic patients from 33 representative hospitals across Australia with a final diagnosis of ACS. Independent predictors of HbA1c assessment were evaluated using a multivariable logistic generalised estimating equations analysis. The association between HbA1c assessment and mortality following discharge was evaluated using Cox proportional hazard analysis. RESULTS: Seven hundred and fourteen (41%) patients had HbA1c assessment during admission. Frequency of assessment varied markedly between hospitals (7.7-87.6%). HbA1c assessment was significantly more frequent in hospitals with catheterisation laboratories. Frequency of assessment was not associated with location of hospital (rural vs urban) or hospital capacity. Independent clinical predictors of HbA1c assessment across participating hospitals were younger age, ST-Elevation Myocardial Infarction, cardiac catheterisation and coronary artery bypass surgery during admission. HbA1c assessment was associated with higher rates of coronary catheterisation, revascularisation and receipt of evidence-based medicines but not with mortality during 6 months following discharge (hazard ratio, 0.48; 95% confidence interval, 0.19-1.18). CONCLUSION: Frequency of HbA1c assessment varies markedly between hospitals, and most diabetic patients admitted for ACS in Australia do not receive assessment of pre-admission glycaemic control. HbA1c assessment was associated with better evidence driven medical care.

Comparison of the management and in-hospital outcomes of acute coronary syndrome patients in Australia and New Zealand: results from the binational SNAPSHOT acute coronary syndrome 2012 audit.

BACKGROUND/AIMS: We aimed to assess differences in patient management, and outcomes, of Australian and New Zealand patients admitted with a suspected or confirmed acute coronary syndrome (ACS). METHODS: We used comprehensive data from the binational Australia and New Zealand ACS 'SNAPSHOT' audit, acquired on individual patients admitted between 00.00 h on 14 May 2012 to 24.00 h on 27 May 2012. RESULTS: There were 4387 patient admissions, 3381 (77%) in Australia and 1006 (23%) in New Zealand; Australian patients were slightly younger (67 vs 69 years, P = 0.0044). Of the 2356 patients with confirmed ACS, Australian patients were at a lower cardiovascular risk with a lower median Global Registry Acute Coronary Events score (147 vs 154 P = 0.0008), but as likely to receive an invasive coronary angiogram (58% vs 54%, P = 0.082), or revascularisation with percutaneous coronary intervention (32% vs 31%, P = 0.92) or coronary artery bypass graft surgery (7.0% vs 5.6%, P = 0.32). Of the 1937 non-segment elevation myocardial infarction/unstable angina pectoris (NSTEMI/UAP) patients, Australian patients had a shorter time to angiography (46 h vs 67 h, P < 0.0001). However, at discharge, Australian NSTEMI/UAP survivors were less likely to receive aspirin (84% vs 89%, P = 0.0079, a second anti-platelet agent (57% vs 63%, P = 0.050) or a beta blocker (67% vs 77%, P = 0.0002). In-hospital death rates were not different (2.7% vs 3.2%, P = 0.55) between Australia and New Zealand. CONCLUSIONS: Overall more similarities were seen, than differences, in the management of suspected or confirmed ACS patients between Australia and New Zealand. However, in several management areas, both countries could improve the service delivery to this high-risk patient group.

The design and rationale of the Australian Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE).

BACKGROUND: Cardiovascular observational registries characterise patients and describe the manner and use of therapeutic strategies. They facilitate analyses on the quality of care among participating institutions and document variations in clinical practice which can be benchmarked against best practice recommendations. The Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE) is an Australian observational registry that describes management and outcomes in patients with acute coronary syndromes (ACS) and feeds back both performance and outcome measures to participating hospitals. METHODS: The CONCORDANCE registry has been designed within a comparative effectiveness research (CER) framework to collect and report data from hospitals located in geographically diverse regions of Australia. Information including patient demographics, presenting characteristics, past medical history, in-hospital management and outcomes at six months and two years are entered into a web-based database using an electronic clinical record form (eCRF). Individual hospital information is returned to the sites in a real time confidential report detailing information on key performance indicator (KPI) process measures and outcomes benchmarked against the aggregated study cohort. Governance rules ensure data security and protect patient and clinician confidentiality. Consistent with a CER framework, additional characteristics of the registry include: (a) the capacity to evaluate associations between the inter and intra hospital systems and the provision of evidence based care and outcomes, (b) ongoing data collection from representative hospitals which allow spatial and temporal analysis of change in practice and the application of treatment modalities in the real world setting and (c) the provision of a data spine for quality improvement strategies and practical clinical trials. CONCLUSION: The CONCORDANCE registry is a clinician-driven initiative describing clinical care for ACS patients admitted to Australian hospitals. The registry generates high quality data which is fed back to clinicians, and key stakeholders in ACS care. Using a CER approach, the registry describes the translation of randomised trial evidence into practice, and provides insights into strategies that could improve care and ultimately patient outcomes.

An invasive management strategy is associated with improved outcomes in high-risk acute coronary syndromes in patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is associated with poor outcomes after acute coronary syndromes, yet selection for invasive investigation and management is low. METHODS: Patients presenting with ST segment elevation myocardial infarction (STEMI) or intermediate- to high-risk non-ST segment elevation acute coronary syndrome (NSTEACS) (n=2597) were stratified into groups based on kidney function, defined as normal (glomerular filtration rate (GFR)≥60mL/min/1.73m(2) ), moderate CKD (GFR 30-59mL/min/1.73m(2) ) and severe CKD (GFR <30mL/min/1.73m(2)). Based on these stratums of kidney function, incidence and outcome measures were obtained for: rates of angiography and revascularization; 6-month mortality; and the incidence and outcome of in-hospital acute kidney impairment (AKI). RESULTS: Patients with CKD were less likely to be offered coronary angiography after STEMI/NSTEACS (P<0.001); however, after selection, revascularization rates were similar (percutaneous coronary intervention (P=0.8); surgery (P=0.4)). Six-month mortality rates increased with CKD (GFR≥60, 2.8%; GFR 30-59, 9.9%; GFR<30, 16.5%, P≤0.001), as well as the combined efficacy/safety end-point (GFR≥60, 9.4%; GFR 30-59, 20.2%; GFR<30, 27.1%, P≤0.001). Six-month mortality was lower in patients who had received prior angiography (GFR≥60, 1.5% vs 3.6%, P=0.001; GFR 30-59, 5.1% vs 12.7%, P<0.001; GFR<30, 7.3% vs 18.5%, P=0.094). Risk of AKI increased with CKD (GFR≥60, 0.7%; GFR 30-59, 3.4%; GFR<30, 6.8%, P≤0.001), and was associated with high 6-month mortality (35.6% vs 4.1%, P<0.001). CONCLUSIONS: In patients with CKD after STEMI/NSTEACS, 6-month mortality and morbidity is high, selection for angiography is lower, yet angiography is associated with a reduced long-term mortality, and with comparable revascularization rates to those without CKD. In-hospital AKI is more common in CKD and predicts a high 6-month mortality.

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.

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.

Current management of acute coronary syndromes in Australia: observations from the acute coronary syndromes prospective audit.

BACKGROUND: Acute coronary syndromes (ACS) management is now well informed by guidelines extrapolated from clinical trials. However, most of these data have been acquired outside the local context. We sought to describe the current patterns of ACS care in Australia. METHODS: The Acute Coronary Syndrome Prospective Audit study is a prospective multi-centre registry of ST-segment elevation myocardial infarction (STEMI), high-risk non-ST-segment elevation ACS (NSTEACS-HR) and intermediate-risk non-ST-segment elevation ACS (NSTEACS-IR) patients, involving 39 metropolitan, regional and rural sites. Data included hospital characteristics, geographic and demographic factors, risk stratification, in-hospital management including invasive services, and clinical outcomes. RESULTS: A cohort of 3402 patients was enrolled; the median age was 65.5 years. Female and non-metropolitan patients comprised 35.5% and 23.9% of the population, respectively. At enrolment, 756 (22.2%) were STEMI patients, 1948 (57.3%) were high-risk NSTEACS patients and 698 (20.5%) were intermediate-risk NSTEACS patients. Evidence-based therapies and invasive management use were highest among suspected STEMI patients compared with other strata (angiography: STEMI 89%, NSTEACS-HR 54%, NSTEACS-IR 34%, P < 0.001) (percutaneous coronary intervention: STEMI 68.1%, NSTEACS-HR 22.2%, NSTEACS-IR 8.1%, P < 0.001). In hospital mortality was low (STEMI 4.0%, NSTEACS-HR 1.8%, NSTEACS-IR 0.1%, P < 0.001), as was recurrent MI (STEMI 2.4%, NSTEACS-HR: 2.8%, NSTEACS-IR 1.2%, P = 0.052). CONCLUSION: There appears to be an 'evidence-practice gap' in the management of ACS, but this is not matched by an increased risk of in-hospital clinical events. Objective evaluation of local clinical care is a key initial step in developing quality improvement initiatives and this study provides a basis for the improvement in ACS management in Australia.

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.

Coronary stenting in diabetic patients: Results from the ROSETTA registry.

OBJECTIVE: Diabetes mellitus is associated with high rates of restenosis and adverse outcomes after percutaneous transluminal coronary angioplasty (PTCA). It is unclear whether coronary stenting reduces adverse events in diabetic patients after PTCA. Our purpose was to determine whether coronary stenting improves clinical event rates in diabetic patients after PTCA. METHODS: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) registry was a prospective multicenter observational study examining functional testing and adverse outcomes after successful PTCA. RESULTS: Among the 791 patients enrolled, 180 were diabetic. A total of 90 diabetics received stents while the remaining 90 patients did not. Baseline clinical characteristics were similar between the 2 groups of patients. However, patients with stents were more likely to have complex lesions, whereas those without stents were more likely to undergo atherectomy and have greater residual coronary stenosis. At 6-month follow-up, the composite end point defined as cardiac death, unstable angina, myocardial infarction, need for repeat PTCA, or coronary artery bypass graft surgery (CABG) occurred in 25.0% of stented and 22.2% of nonstented diabetic patients (P not significant [NS]). A multivariate logistic regression analysis showed that coronary stenting was not associated with a reduced incidence of the composite end point among diabetic patients (odds ratio 0.97, 95% CI 0.46-2.05, P NS). CONCLUSION: Coronary stenting does not improve clinical event rates in diabetic patients after PTCA.

Characterisation of persistent anti-Xa activity following administration of the low molecular weight heparin enoxaparin sodium (Clexane).

It is widely reported that persistent anti-Xa activity follows administration of low molecular weight heparins. To identify the effectors of this activity we have injected 125I-labelled Enoxaparin sodium into rabbits and subsequently analysed the circulating radiolabelled material and anti-Xa activity by affinity and size exclusion chromatography. Antithrombin III-binding material derived from the injected drug was responsible for all the anti-Xa amidolytic activity. At early times after injection additional anticoagulant activity which was largely attributable to tissue factor pathway inhibitor was measured by the Heptest clotting assay after removal of glycosaminoglycans from plasma samples. Small radiolabelled fragments, including penta/hexasaccharide with affinity for antithrombin III, were detectable in the circulation 1 week later, and sulphated oligosaccharides persisted for 3-4 weeks. Significant quantities of radiolabel remained in the liver and kidney several weeks post-injection; these organs may sequester some of the injected drug and give rise to circulating biologically active material by degradation and secretion of catabolic products into the plasma.

Production method affects the pharmacokinetic and ex vivo biological properties of low molecular weight heparins.

Low molecular weight (LMW) heparins have prolonged circulating half-lives relative to unfractionated heparin, but the rates of plasma clearance differ between different LMW preparations. To determine the impact of method of production on their pharmacokinetic and ex vivo biological properties, two LMW heparins of similar molecular weight distribution, Logiparin and Fragmin, were radiolabelled with 125I, administered intravenously with 4 mg/kg of carrier drug into rabbits, and the circulating radiolabelled material and anti-Xa activity were analysed by size exclusion chromatography and affinity for antithrombin and Polybrene. Following administration of Logiparin, the anti-Xa amidolytic activity was eliminated with the same half-life as the anti-thrombin-binding radiolabel and was not neutralised by antibody against tissue factor pathway inhibitor (TFPI). Larger molecules were cleared preferentially and were no longer detectable 8 h post injection. These findings resemble those we have previously described for Enoxaparin. After Fragmin administration the antithrombin binding radiolabel was cleared more rapidly than the anti-Xa activity, and at late times after injection a significant amount of this activity was neutralised by antibody against TFPI. Sulphated radiolabel was eliminated with a similar half-life to the anti-Xa activity and sulphated molecules > 6000 Da remained in the circulation 8 h after administration. Fragmin, unlike Logiparin and Enoxaparin, has no negatively charged sulphamino group at the reducing end of the molecule. We suggest that this minimises cellular interaction and protects the larger molecules from elimination. They remain in the circulation, contributing to anti-Xa activity by binding TFPI. Thus the method of production of LMW heparins may significantly influence their pharmacokinetic properties and circulating anticoagulant activities.

Low molecular weight heparin is responsible for the anti-Xa activity of Desmin 370.

Dermatan sulphate does not catalyse the inactivation of factor Xa. However, the low molecular weight (LMW) dermatan sulphate Desmin 370 has been shown to generate circulating anti-Xa activity following administration to humans. Using a single batch of Desmin 370, we measured 3 U/mg of anti-Xa activity by amidolytic assay in vitro. The material responsible for this activity had a lower molecular weight range (6000 and 1800 Da) than Desmin 370 and was more highly sulphated than the bulk of the drug. Heparinase digestion of Desmin 370 eliminated 90% of the in vitro anti-Xa activity without significantly interfering with its ability to potentiate inactivation of thrombin by HCII, suggesting that the anti-Xa activity is not due to dermatan sulphate and is probably heparin. When 125I-labelled Desmin 370 together with 40 mg/kg carrier drug was administered intravenously to a rabbit, anti-Xa activity was readily detectable in the plasma for up to 10 h and had a longer half-life than the sulphated radiolabel. Most of this anticoagulant activity was recovered from the plasma by Polybrene affinity chromatography and was probably a sulphated glycosaminoglycan. Administration of the heparinase-digested drug to a rabbit resulted in 70% less anti-Xa activity than the undigested drug. We conclude that Desmin 370 contains detectable quantities of biologically active low molecular weight heparin, which is responsible for persistent anti-Xa activity following intravenous administration.

Long-term persistence of biological activity following administration of Enoxaparin sodium (clexane) is due to sequestration of antithrombin-binding low molecular weight fragments--comparison with unfractionated heparin.

We have previously reported (Brieger D, Dawes J. Thromb Haemost 1994; 72: 275-80) that the prolonged anti-Xa amidolytic activity following intravenous administration of the low molecular weight heparin Enoxaparin sodium is mediated by small molecules derived from the injected drug, and an antithrombin binding penta/hexasaccharide can be detected in the circulation as late as 1 week after administration. To investigate the mechanism underlying this persistence we administered 125I-labelled fractions of Enoxaparin sodium and unfractionated 125I-heparin to rabbits. Both 125I-heparin and the radiolabeled high molecular weight (> 6000 Da) Enoxaparin sodium were more effectively cleared from the circulation than the smaller components of LMW heparin. However, our data suggest that the circulating biologically active penta/hexasaccharide was not an unmodified component of the injected drug but was derived from a subpopulation of molecules of intermediate molecular weight (1800-6000 Da) which was retained in the tissues. Significant quantities of both Enoxaparin sodium and unfractionated heparin were retained in the internal organs. We propose that the sequestered subpopulations of Enoxaparin sodium and unfractionated heparin follow different catabolic routes. After administration of both unfractionated and LMW heparin additional antithrombin binding material was released into the circulation by a bolus dose of heparin. This material was not contained on circulating blood cells and was probably sequestered on the endothelium.

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.

Minimally invasive management of transposition of the great arteries in the newborn period.

This study reports on a predominantly noninvasive management program for neonatal transposition of the great arteries [TGA] incorporating balloon atrial septostomy [BAS] under echocardiographic control. BAS was performed in 25 consecutive patients presenting with TGA between April 1988 and April 1990. Structural and coronary anatomy was evaluated echocardiographically with angiographic supplementation only when additional data were required. This information was correlated, where possible, with direct anatomic findings and subsequent course. BAS was performed through the umbilicus in 17 patients (85% of patients in whom this approach was attempted). Thirteen patients did not require ventilation during BAS. There were minimal complications and satisfactory septostomies in all cases. Coronary anatomy was correctly predicted in all patients where anatomic correlation was available. Without invasive investigation 9 patients underwent neonatal arterial switch procedures and 2 underwent palliative procedures. BAS under echocardiographic control proved safe, effective, minimally traumatic and mostly possible via the umbilical vein. The umbilical vein, where patent, permitted rapid safe access for BAS. Echocardiographic diagnosis of the coronary artery, and structural and functional anatomy was reliable and allowed minimally invasive preoperative management in many patients.

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.

Hirudin in Acute Coronary Syndromes: When Cents Override Good Sense.

Two large multicenter clinical trials comparing heparin with hirudin in the management of patients with acute coronary syndromes have recently been completed. Direct thrombin inhibition was reported to result in only a modest reduction in the incidence of primary endpoint in GUSTO IIb, and to be of no demonstrable benefit in TIMI 9b. However, closer examination of the performance of hirudin in these trials suggests it to have been harshly judged. Hirudin provided a consistently more reliable anticoagulant effect than heparin, was associated with a comparable risk of bleeding and minimal risk of allergy. Furthermore, direct thrombin inhibition was more effective in preventing events in patients with unstable angina and non-Q wave infarction, and resulted in a significant reduction in the incidence of reinfarction among all facets of the acute coronary syndromes. There was in addition a striking benefit of combining hirudin with streptokinase in patients with acute myocardial infarction. Based on these data, there is little doubt that hirudin rather than heparin should form the foundation on which to base future strategies for management of the acute coronary syndromes.