Outcome trial data on sodium glucose cotransporter-2 inhibitors: Putting clinical benefits and risks in perspective.

BACKGROUND: Sodium glucose cotransporter-2 (SGLT2) inhibitors have significant heart failure and renoprotective benefits with a wide spectrum of unfamiliar and potentially serious adverse effects. Limited understanding of the risk-benefit profile of SGLT2 inhibitor treatment may result in under utilisation by prescribers and patients. METHODS: Data from recent seminal randomized, placebo-controlled, outcome trials for multiple SGLT2 inhibitors were incorporated. Trial populations were sub-classified into high cardiovascular risk T2DM, HFrEF, and CKD. Efficacy outcomes of heart failure hospitalisation (HFH), cardiovascular (CV) mortality, total mortality, and prevention of renal deterioration were examined. Safety outcomes included were major hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infections (UTI), mycotic genital infections (MGI), hypotension, amputations and fractures. Absolute risk reduction/increase were used to calculate number needed to treat/harm. RESULTS: Trial data comprised 71,545 patients, of which 53,144 were high risk T2DM, 9696 HFrEF and 8705 CKD. For HFrEF, NNT for HFH was 18, CV mortality 93, total mortality 76, prevention of renal deterioration 143 and prevention of DKA 6224. NNH for UTI was 557, MGI 356, hypotension 120, hypoglycaemia 574, amputations 707 and fractures 858. For CKD, NNT for HFH was 116, CV mortality 245, total mortality 138, and prevention of renal deterioration was 63. NNH for DKA was 1458, UTI 309, MGI 291, hypotension 165, hypoglycaemia 374, amputations 4450 and fractures 696. In the T2DM cohort, NNT for HFH was 139, CV mortality 851, total mortality 601 and prevention of renal deterioration 558. NNH DKA was 1525, UTI 239, MGI 69, hypotension 325, hypoglycaemia 472, amputations 1578 and fractures 9569. CONCLUSIONS AND RELEVANCE: The cardiovascular and renal protective benefits of SGLT2 inhibitors far outweigh the risks. This paper puts into perspective the benefits and risks of treatment with SGLT2 inhibitors for clinicians and patients.

Artificial intelligence in cardiovascular imaging: state of the art and implications for the imaging cardiologist.

Healthcare, conceivably more than any other area of human endeavour, has the greatest potential to be affected by artificial intelligence (AI). This potential has been shown by several reports that demonstrate equal or superhuman performance in medical tasks that aim to improve efficiency, diagnosis and prognosis. This review focuses on the state of the art of AI applications in cardiovascular imaging. It provides an overview of the current applications and studies performed, including the potential value, implications, limitations and future directions of AI in cardiovascular imaging.It is envisioned that AI will dramatically change the way doctors practise medicine. In the short term, it will assist physicians with easy tasks, such as automating measurements, making predictions based on big data, and putting clinical findings into an evidence-based context. In the long term, AI will not only assist doctors, it has the potential to significantly improve access to health and well-being data for patients and their caretakers. This empowers patients. From a physician's perspective, reliable AI assistance will be available to support clinical decision-making. Although cardiovascular studies implementing AI are increasing in number, the applications have only just started to penetrate contemporary clinical care.

Subspecialisation in cardiology care and outcome: should clinical services be redesigned, again?

BACKGROUND: Inpatient management of cardiac patients by cardiologists results in reduced mortality and hospitalisation. With increasing subspecialisation of the field because of growing management complexity and use of technological innovations, the impact of sub-specialisation on patient outcomes is unclear. AIM: To investigate whether management by subspecialty cardiologists impacts the outcomes of patients with subspecialty-specific diseases. METHODS: All patients admitted to a tertiary centre over nine years with a diagnosis of heart failure, acute coronary syndrome (ACS) or primary arrhythmia were reviewed. The outcomes of these patients managed by cardiologists subspecialised in their admission diagnosis (heart failure specialists, interventionalists and electrophysiologists) were compared with those treated by general cardiologists. RESULTS: Heart failure was diagnosed in 1704 patients, ACS in 7763 and arrhythmia in 4398. There was no difference in length of stay (LOS) (P = 0.26), mortality (P = 0.57) or cardiovascular readmissions (P = 0.50) in heart failure patients treated by general cardiologists compared with subspecialists. In ACS patients, subspecialty management was associated with reduced LOS, cardiovascular readmissions and mortality (all P < 0.05). This reduction in mortality was seen mainly in lower risk patients (P < 0.05). There was a reduction in LOS and cardiovascular readmissions in arrhythmia patients receiving subspecialty management (both P < 0.05) but no difference in mortality (P = 0.14). ACS patients managed by interventionalists were more likely to undergo coronary intervention (P < 0.05). Electrophysiologists more frequently referred patients for catheter ablation and pacemaker implantation than general cardiologists (P < 0.05). CONCLUSIONS: The benefits of subspecialty care seem attributable to the appropriate selection of patients who would benefit from technological innovations in care. These results suggest that the development of healthcare systems which align cardiovascular disease with the subspecialist may be more effective.

Initial experience with the balloon expandable Edwards-SAPIEN Transcatheter Heart Valve in Australia and New Zealand: the SOURCE ANZ registry: outcomes at 30 days and one year.

BACKGROUND: We report the findings of the SOURCE-ANZ registry of the clinical outcomes of the Edwards SAPIEN™ Transcatheter Heart Valve (THV) in the Australian and New Zealand (ANZ) clinical environment. METHODS: This single arm registry of select patients treated in eight centres, represent the initial experience within ANZ with the balloon expandable Edwards SAPIEN THV delivered by transfemoral (TF) and transapical (TA) access. RESULTS: The total enrolment for the study was 132 patients, 63 patients treated by TF, 56 by TA, and 2 patients were withdrawn from the study. The mean ages: 83.7 (TF) and 81.7 (TA), female: 34.3% (TF) and 61.3% (TA), logistic EuroSCORE: 26.8% (TF) and 28.8% (TA), and with procedural success (successful implant without conversion to surgery or death): 92.4% (TF) and 87.1% (TA) (p=0.32). Outcomes were not significantly different between TF and TA implants. These included one year mortality of 13.6% (TF) and 21.7% (TA) (p=0.24), MACCE: 16.7% (TF) and 28.3% (TA) (p=0.12), pacemaker: 4.6% (TF) and 8.3% (TA) (p=0.39), and VARC major vascular complication of 4.6% (TF) and 5.0% (TA) (p=0.91). CONCLUSION: TAVI in the ANZ clinical environment has demonstrated excellent outcomes for both the TA and TF approaches in highly selected patients. These results are consistent with those demonstrated in European, Canadian registries and the pivotal US clinical trials. ACTRN12611001026910.

Impact of age, gender and indigenous status on access to diagnostic coronary angiography for patients presenting with non-ST segment elevation acute coronary syndromes in Australia.

Using Australian guidelines for management of acute coronary syndromes, we investigated the proportion of high-risk patients enrolled in the Acute Coronary Syndromes Prospective Audit registry who received a coronary angiogram. A prospective nationwide multicentre registry involving 39 Australian hospitals was used. The study cohort were patients with high-risk clinical features without ST segment elevation (n = 1948) admitted from emergency departments between 1 November 2005 and 31 July 2007. Eighty nine per cent of patients with ST segment elevation myocardial infarction and only 53% of eligible patients with high-risk acute coronary syndromes with no ST elevation received a diagnostic angiogram. Increasing age was associated with lower rates of angiography; a high-risk patient at the age of ≥ 70 years was 19% less likely to receive an angiogram than one at the age of <70 years (risk ratio (RR) = 0.81 95% confidence interval (CI) 0.76, 0.76). Women were 26% less likely than men to receive an angiogram (RR = 0.74; 95% CI = 0.65, 0.83). The adjusted RR from the multivariate analysis suggests that a patient at the age of ≥ 70 years was 35% less likely to receive an angiogram than one at the age of <70 years (RR = 0.65, 95% CI = 0.60, 0.73), and that women were 13% less likely than men to receive an angiogram (RR = 0.87, 95% CI = 0.80, 0.96). Indigenous patients were as likely to access angiography as eligible non-indigenous patients (RR = 1.03, 95% CI 0.85, 1.25). There is underinvestigation of high-risk patients without ST segment elevation in Australian hospitals, particularly for women and older patients. Indigenous patients are younger and have poorer risk profiles, and represent a group that would benefit from greater investment in prevention strategies.

Patterns of inflammatory activation associated with precipitants of acute coronary syndromes: a case-crossover study.

AIMS: We sought to assess a broad array of possible precipitants of acute coronary syndromes (ACS) and evaluate their association with detectable inflammatory activation. METHODS AND RESULTS: Within a case-crossover design, using a standardised questionnaire, interviews among 348 ST-elevation myocardial infarction (44%) or high-risk non-ST-elevation ACS patients (56%), explored potential precipitants, including: infection (INF)-temperature >38°C and/or respiratory tract, urinary or skin infection; inflammation (INFL)-exacerbation of inflammatory conditions; exercise (EX)-moderate to heavy exercise; fast food (FF)-consumption of a meal purchased from a fast food company. Risk and control periods were: weekly over 8 weeks for INF and INFL; 24 hourly over 4 days for FF and 4 hourly over 48 h for EX. C-reactive protein (CRP) levels were assessed at admission. These precipitants were identified in 203/348 (58.3%) patients. An increased temporal risk was observed for: INF (0-7 days vs 7-8 weeks odds ratio (OR): 7.5, confidence interval (CI): 1.7-67.6, P = 0.002); INFL (0-7 days vs 7-8 weeks OR: 14.0, CI: 2.13-591.9, P = 0.001); EX (0-4 h vs 24-28 h OR: 2.2, CI: 1.3-3.5, P = 0.001) and FF (0-24 h vs 72-96 h OR: 5.67, CI: 1.6-30.2, P = 0.003). CRP levels were significantly elevated among patients reporting infective and inflammatory potential precipitants, but not among those reporting fast food consumption and unaccustomed moderate-heavy exercise. CONCLUSION: Infection, inflammatory conditions, moderate-heavy exercise and potentially fast food consumption appear to precipitate high-risk ACS. Increased inflammation as measured by CRP was not consistently detected despite the identification of an ACS precipitant. Strategies that target improved overall health may also lead to fewer ACS events through a reduction in triggers.

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.

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.

Six-month survival benefits associated with clinical guideline recommendations in acute coronary syndromes.

AIMS: The authors sought to define which guideline-advocated therapies are associated with the greatest benefit with respect to 6-month survival in patients hospitalised with an acute coronary syndrome (ACS). METHODS AND RESULTS: The authors conducted a nested case-control study of ACS patients within the Global Registry of Acute Coronary Events cohort between April 1999 and December 2007. The cases were ACS patients who survived to discharge but died within 6 months. The controls were patients who survived to 6 months, matched for ACS diagnosis, age and the Global Registry of Acute Coronary Events risk score. Rates of use of evidence-based medications and coronary interventions (angiography, percutaneous coronary intervention and coronary artery bypass graft surgery) were compared. Logistic regression including matched variables was used, and the attributable mortality from incomplete application of each therapy was calculated. A total of 1716 cases and 3432 controls were identified. Coronary artery bypass graft surgery and percutaneous coronary intervention were associated with the greatest 6-month survival benefit (OR for death 0.60 (95% CI 0.39 to 0.90) and 0.57 (0.48 to 0.72), respectively). Statins and clopidogrel provided the greatest independent pharmacologic benefit (ORs for death 0.85 (0.73 to 0.99) and 0.84 (0.72 to 0.99)) with lesser effects seen with other pharmacotherapies. CONCLUSIONS: A diminishing benefit associated with each additional ACS therapy is evident. These data may provide a rational basis for selecting between therapeutic options when compliance or cost is an issue.

Six-month survival benefits associated with clinical guideline recommendations in acute coronary syndromes

AIMS: The authors sought to define which guideline-advocated therapies are associated with the greatest benefit with respect to 6-month survival in patients hospitalised with an acute coronary syndrome (ACS).METHODS AND RESULTS: The authors conducted a nested case-control study of ACS patients within the Global Registry of Acute Coronary Events cohort between April 1999 and December 2007. The cases were ACS patients who survived to discharge but died within 6 months. The controls were patients who survived to 6 months, matched for ACS diagnosis, age and the Global Registry of Acute Coronary Events risk score. Rates of use of evidence-based medications and coronary interventions (angiography, percutaneous coronary intervention and coronary artery bypass graft surgery) were compared. Logistic regression including matched variables was used, and the attributable mortality from incomplete application of each therapy was calculated. A total of 1716 cases and 3432 controls were identified. Coronary artery bypass graft surgery and percutaneous coronary intervention were associated with the greatest 6-month survival benefit (OR for death 0.60 (95% CI 0.39 to 0.90) and 0.57 (0.48 to 0.72), respectively). Statins and clopidogrel provided the greatest independent pharmacologic benefit (ORs for death 0.85 (0.73 to 0.99) and 0.84 (0.72 to 0.99)) with lesser effects seen with other pharmacotherapies.CONCLUSIONS: A diminishing benefit associated with each additional ACS therapy is evident. These data may provide a rational basis for selecting between therapeutic options when compliance or cost is an issue.

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.

Potential survival gains in the treatment of myocardial infarction.

OBJECTIVES: To evaluate the potential impact of complete implementation of guideline recommendations in myocardial infarction (MI) care, and contrast this with new innovations. DESIGN: Modelling of potential events prevented from literature-based treatment effects and observed guideline recommendation utilisation rates. SETTING: Hospital-based care. PARTICIPANTS: Nationwide registry of 1630 patients with MI adjusted for age, gender and GRACE score extrapolated to a population of 10 000 patients. INTERVENTIONS: Literature-based efficacy estimates associated with guideline-recommended treatments and a putative treatment providing a 10-30% 12-month event reduction. MAIN OUTCOME MEASURES: Mortality and recurrent MI or stroke by 30 days and 30 days to 12 months. RESULTS: Adjusted-mortality rates for optimally managed patients with ST-segment MI (STEMI) and non-ST-segment MI (NSTEMI) to 30 days were 0.6% and 2.5%, respectively. Adjusted mortality from 30 days to 12 months was 1.8% among optimally managed patients. No reperfusion occurred in 31% of patients with STEMI. Fewer than four guideline treatments were prescribed in 26% of patients at discharge. Compared with in-hospital care, better application of secondary prevention treatments provided the greater absolute gains (STEMI 23 lives/10 000 patients by 30 days, NSTEMI 43 lives/10 000 by 30 days and secondary prevention 104 lives/10 000 by 12 months). A putative novel treatment reducing mortality by 30% among optimally managed patients would save a further 4 lives/10 000 by 12 months. CONCLUSIONS: Potential gains from improved clinical effectiveness in MI care are likely to compare favourably with benefits achieved though innovations, and should inform priorities in research and implementation strategies for improving MI outcomes.

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.

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.

Improving the management of acute coronary syndromes in Australia: translating evidence to outcomes.

Cardiovascular disease imposes a heavy burden of morbidity and mortality on the Australian community. This situation is likely to exacerbate as the number of elderly Australians increase. Management of acute coronary syndromes (ACS) is underpinned by a robust evidence base, which is outlined in clinical practice guidelines. Yet, despite wide diffusion of guidelines, many Australians who experience acute coronary syndromes do not receive optimal care. This article reviews what we have learnt from previous quality improvement initiatives and discusses what we need to know to improve acute coronary syndromes management in Australia.

Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.

BACKGROUND: Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. AIMS: We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. METHODS: A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. RESULTS: Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. CONCLUSION: Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.

The foundation and launch of the Melbourne Interventional Group: a collaborative interventional cardiology project.

The Melbourne Interventional Group (MIG) is a voluntary collaborative venture of interventional cardiologists practicing at 12 major public and private hospitals in Victoria, designed to record data pertaining to percutaneous coronary interventions (PCI) and perform long-term follow-up. The potential advantages of collaboration involve large-scale analysis of current interventional strategies (e.g. drug-eluting stents, evaluation of new technologies and cost-effective analysis), provide a basis for multi-centred clinical trials and allow comparison of clinical outcomes with cardiac surgery. The established registry documents demographic, clinical and procedural characteristics of consecutive patients undergoing PCI and permits analysis of those characteristics at 30 days and 12 months. The registry is co-ordinated by the Centre of Clinical Research Excellence (CCRE), a research body within the Department of Epidemiology and Preventive Medicine (Monash University, Melbourne). The eventual goal of MIG is to provide a contemporary appraisal of Australian interventional cardiology practice, with opportunities to improve in-hospital and long-term outcomes of patients with coronary artery disease.

Clinical end point definitions after percutaneous coronary intervention and their relationship to late mortality: an assessment by attributable risk.

OBJECTIVES: To explore the relative and absolute risks associated with various definitions for myocardial infarction, bleeding and revascularisation within the context of percutaneous coronary intervention (PCI). METHODS: The REPLACE-2 (randomised evaluation of PCI linking Angiomax to reduced clinical events) database of patients undergoing PCI was used. Various definitions of myocardial infarction, bleeding and revascularisation were modelled by logistic regression assessing their relationship with 12-month mortality. Estimates from these models were used to calculate the "attributable fraction" for late mortality associated with each definition. RESULTS: The most liberal definition of myocardial infarction was associated with an attributable risk of 13.7% (95% CI 3.4% to 23.0%). The most stringent definition was associated with an attributable risk of 4.6% (95% CI 0.6% to 8.6%). Restrictive definitions of bleeding such as TIMI (thrombolysis in myocardial infarction) major bleeding are associated with a high odds ratio of risk (6.1, 95% CI 2.1 to 17.7, p = 0.001) but low attributable fraction (3.5%, 95% CI 0.9% to 6.8%). CONCLUSIONS: Stringent end point definitions may under-represent the clinical significance of adverse outcomes after PCI. Considering both the proportional and absolute risk associated with definitions may be a more useful method for evaluating clinical trial end points. This analysis supports the current definitions of ischaemic events but suggests that more liberal definitions of bleeding events may also be relevant to late mortality.

Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes. Gradient of benefit related to the revascularization strategy.

AIMS: To assess the efficacy of platelet glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed. METHODS AND RESULTS: We performed a meta-analysis of the randomized clinical trials of platelet glycoprotein IIb/IIIa inhibitor therapy in the medical management of non-ST-elevation acute coronary syndromes. Among 29570 patients, IIb/IIIa integrin blockade was associated with a reduction in death or non-fatal myocardial infarction at 30 days, from 11.5% to 10.7% (odds ratio 0.91,P =0.02). Patients undergoing percutaneous coronary intervention during index hospitalization sustained a greater reduction in ischaemic events (odds ratio 0.82, P=0.01) than patients medically managed (odds ratio 0.95, P=0.27). Among patients undergoing intervention, the benefit was more pronounced if the procedure was performed during glycoprotein IIb/IIIa inhibitor infusion (odds ratio 0.74; P=0.02), than if revascularization was performed after drug discontinuation (odds ratio 0.87,P =0.17). CONCLUSION: This analysis, including the entire large-scale trial experience of intravenous glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes primarily medically managed, demonstrates an overall significant, albeit moderate, reduction in 30-day death or myocardial infarction associated with therapy. Although not based on a prospectively defined hypothesis, the findings suggest a gradient of benefit conferred by these agents depending on the revascularization strategy used.

Bivalirudin, a bivalent, thrombin specific anticoagulant as an alternative to heparin in interventional procedures as an alternative to heparin in interventional procedures.

Among the antithrombotic therapies evaluated to date, the synthetic peptide bivalirudin is unique in its ability to reduce both ischemic and bleeding complications associated with percutaneous coronary intervention (PCI). Bivalirudin is a small peptide consisting of 20 amino acid residues that binds thrombin in a direct, reversible, and bivalent fashion. The agent is approved for use in the United States and New Zealand as an anticoagulant in patients with unstable angina undergoing PCI and may also prove beneficial in patients with acute coronary syndromes (ACS), acute myocardial infarction (AMI) and in patients undergoing coronary artery bypass graft (CABG) procedures. This article examines bivalirudin in more detail.