Gordon FitzGerald

Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events

Objective: To assess whether sex differences exist in the angiographic severity, management and outcomes of acute coronary syndromes (ACS). Methods: The study comprised 7638 women and 19 117 men with ACS who underwent coronary angiography and were included in GRACE (Global Registry of Acute Coronary Events) from 1999–2006. Normal vessels/mild disease was defined as <50% stenosis in all epicardial vessels; advanced disease was defined as ⩾one vessel with ⩾50% stenosis. Results: Women were older than men and had higher rates of cardiovascular risk factors. Men and women presented equally with chest pain; however, jaw pain and nausea were more frequent among women. Women were more likely to have normal/mild disease (12% vs 6%, p<0.001) and less likely to have left-main and three-vessel disease (27% vs 32%, p<0.001) or undergo percutaneous coronary intervention (65% vs 68%, p<0.001). Women and men with normal and mild disease were treated less aggressively than those with advanced disease. Women with advanced disease had a higher risk of death (4% vs 3%, p<0.01). After adjustment for age and extent of disease, women were more likely to have adverse outcomes (death, myocardial infarction, stroke and rehospitalisation) at six months compared to men (odds ratio 1.24, 95% confidence interval 1.14 to 1.34); however, sex differences in mortality were no longer statistically significant. Conclusions: Women with ACS were more likely to have cardiovascular disease risk factors and atypical symptoms such as nausea compared with men, but were more likely to have normal/mild angiographic coronary artery disease. Further study regarding sex differences related to disease severity is warranted.

Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: FINDINGS FROM THE GLOBAL ORTHOPAEDIC REGISTRY

Patients who have undergone total hip or knee replacement (THR and TKR, respectively) are at high risk of venous thromboembolism. We aimed to determine the time courses of both the incidence of venous thromboembolism and effective prophylaxis. Patients with elective primary THR and TKR were enrolled in the multi-national Global Orthopaedic Registry. Data on the incidence of venous thromboembolism and prophylaxis were collected from 6639 THR and 8326 TKR patients. The cumulative incidence of venous thromboembolism within three months of surgery was 1.7% in the THR and 2.3% in the TKR patients. The mean times to venous thromboembolism were 21.5 days (sd 22.5) for THR, and 9.7 days (sd 14.1) for TKR. It occurred after the median time to discharge in 75% of the THR and 57% of the TKA patients who developed venous thromboembolism. Of those who received recommended forms of prophylaxis, approximately one-quarter (26% of THR and 27% of TKR patients) were not receiving it seven days after surgery, the minimum duration recommended at the time of the study. The risk of venous thromboembolism extends beyond the usual period of hospitalisation, while the duration of prophylaxis is often shorter than this. Practices should be re-assessed to ensure that patients receive appropriate durations of prophylaxis.

Does Comorbidity Account for the Excess Mortality in Patients With Major Bleeding in Acute Myocardial Infarction

Background— Analyses from randomized controlled trials suggest that bleeding in patients with acute myocardial infarction is associated with poor outcomes. Because these data are not generalizable to all patients with acute myocardial infarction, we sought to better understand the scope of this problem in a “real-world” setting. Methods and Results— We examined the frequency of major bleeding in 40 087 patients with acute myocardial infarction enrolled in the Global Registry of Acute Coronary Events. Regression analyses were used to examine the association between patient and treatment characteristics, bleeding, and hospital and postdischarge outcomes. Major bleeding occurred in 2.8% of patients. These patients were older, more severely ill, and more likely to undergo invasive procedures. Patients with bleeding were more likely to die during hospitalization (hazard ratio, 1.9; 95% confidence interval, 1.6 to 2.2) but not after discharge (hazard ratio, 0.8; 95% confidence interval, 0.6 to 1.0) than patients who did not bleed. Continuation of antithrombotic therapies after day 1 was lower in patients who experienced early bleeding. Moreover, in patients who bled, hospital mortality was increased in those who discontinued aspirin, thienopyridines, or low–molecular-weight heparins. Conclusions— Major bleeding occurred in 1 in 35 patients with acute myocardial infarction; these patients accounted for ≈10% of all hospital deaths. Nevertheless, risk of hospital mortality associated with bleeding was much lower than reported in randomized controlled trials. These data suggest that although bleeding may be causally related to adverse outcomes in some patients in the real-world setting, it is often merely a marker for patients at higher risk for adverse outcomes.

Factors at Admission Associated With Bleeding Risk in Medical Patients: Findings From the IMPROVE Investigators

BACKGROUND Acutely ill, hospitalized medical patients are at risk of VTE. Despite guidelines for VTE prevention, prophylaxis use in these patients is still poor, possibly because of fear of bleeding risk. We used data from the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) to assess in-hospital bleeding incidence and to identify risk factors at admission associated with in-hospital bleeding risk in acutely ill medical patients. METHODS IMPROVE is a multinational, observational study that enrolled 15,156 medical patients. The in-hospital bleeding incidence was estimated by Kaplan-Meier analysis. A multiple regression model analysis was performed to identify risk factors at admission associated with bleeding. RESULTS The cumulative incidence of major and nonmajor in-hospital bleeding within 14 days of admission was 3.2%. Active gastroduodenal ulcer (OR, 4.15; 95% CI, 2.21-7.77), prior bleeding (OR, 3.64; 95% CI, 2.21-5.99), and low platelet count (OR, 3.37; 95% CI, 1.84-6.18) were the strongest independent risk factors at admission for bleeding. Other bleeding risk factors were increased age, hepatic or renal failure, ICU stay, central venous catheter, rheumatic disease, cancer, and male sex. Using these bleeding risk factors, a risk score was developed to estimate bleeding risk. CONCLUSIONS We assessed the incidence of major and clinically relevant bleeding in a large population of hospitalized medical patients and identified risk factors at admission associated with in-hospital bleeding. This information may assist physicians in deciding whether to use mechanical or pharmacologic VTE prophylaxis.

Predictive and Associative Models to Identify Hospitalized Medical Patients at Risk for VTE

BACKGROUND Acutely ill hospitalized medical patients are at risk for VTE. We assessed the incidence of VTE in the observational International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) study and derived VTE risk assessment scores at admission and associative VTE scores during hospitalization. METHODS Data from 15,156 medical patients were analyzed to determine the cumulative incidence of clinically observed VTE over 3 months after admission. Multiple regression analysis identified factors associated with VTE risk. RESULTS Of the 184 patients who developed symptomatic VTE, 76 had pulmonary embolism, and 67 had lower-extremity DVT. Cumulative VTE incidence was 1.0%; 45% of events occurred after discharge. Factors independently associated with VTE were previous VTE, known thrombophilia, cancer, age > 60 years, lower-limb paralysis, immobilization ≥ 7 days, and admission to an ICU or coronary care unit (first four were available at admission). Points were assigned to each factor identified to give a total risk score for each patient. At admission, 67% of patients had a score ≥ 1. During hospitalization, 31% had a score ≥ 2; for a score of 2 or 3, observed VTE risk was 1.5% vs 5.7% for a score ≥ 4. Observed and predicted rates were similar for both models (C statistic, 0.65 and 0.69, respectively). During hospitalization, a score ≥ 2 was associated with higher overall and VTE-related mortality. CONCLUSIONS Weighted VTE risk scores derived from four clinical risk factors at hospital admission can predict VTE risk in acutely ill hospitalized medical patients. Scores derived from seven clinical factors during hospitalization may help us to further understand symptomatic VTE risk. These scores require external validation.

Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty

ABSTRACT Objective: Despite evidence-based guidelines for venous thromboembolism (VTE) prevention after total hip or knee arthroplasty (THA/TKA), many patients may not receive effective prophylaxis. Our objective was to analyze data from the multinational Global Orthopaedic Registry (GLORY) to evaluate the compliance of surgeons with the American College of Chest Physicians (ACCP) guidelines for VTE prevention. Research design and methods: Data from 8160 patients who had undergone a primary, unilateral, elective THA (n = 3950) or TKA (n = 4210), and had at least 3 months of follow-up were analyzed. Results: Almost all patients received a form of recommended prophylaxis. Compliance with guidelines in terms of type, duration, start time, and dose was achieved for 47% of THA and 61% of TKA patients in the USA, and 62% of THA and 69% of TKA patients outside the USA. Warfarin use, mostly in the USA, was fully compliant in 33% of THA and 48% of TKA patients. Low-molecular-weight heparin use was fully compliant in 63% of THA and 72% of TKA patients in the USA, and 67% of THA and 73% of TKA patients outside the USA. Conclusion: Although almost all THA and TKA patients both inside and outside the USA received prophylaxis, a large proportion did not receive treatment in accordance with the ACCP guidelines. Our study may have overestimated the use of recommended prophylaxis as some participating investigators may have had a specific interest in VTE prophylaxis. Furthermore, although analyses were restricted to approximately three-quarters of patients who had outpatient follow-up data, their characteristics were similar to those in the entire population.

Unprotected left main revascularization in patients with acute coronary syndromes

AIMS In acute coronary syndromes (ACS), the optimal revascularization strategy for unprotected left main coronary disease (ULMCD) has been little studied. The objectives of the present study were to describe the practice of ULMCD revascularization in ACS patients and its evolution over an 8-year period, analyse the prognosis of this population and determine the effect of revascularization on outcome. METHODS AND RESULTS Of 43 018 patients enrolled in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007, 1799 had significant ULMCD and underwent percutaneous coronary intervention (PCI) alone (n = 514), coronary artery bypass graft (CABG) alone (n = 612), or no revascularization (n = 673). Mortality was 7.7% in hospital and 14% at 6 months. Over the 8-year study, the GRACE risk score remained constant, but there was a steady shift to more PCI than CABG over time. Patients undergoing PCI presented more frequently with ST-segment elevation myocardial infarction (STEMI), after cardiac arrest, or in cardiogenic shock; 48% of PCI patients underwent revascularization on the day of admission vs. 5.1% in the CABG group. After adjustment, revascularization was associated with an early hazard of hospital death vs. no revascularization, significant for PCI (hazard ratio (HR) 2.60, 95% confidence interval (CI) 1.62-4.18) but not for CABG (1.26, 0.72-2.22). From discharge to 6 months, both PCI (HR 0.45, 95% CI 0.23-0.85) and CABG (0.11, 0.04-0.28) were significantly associated with improved survival in comparison with an initial strategy of no revascularization. Coronary artery bypass graft revascularization was associated with a five-fold increase in stroke compared with the other two groups. CONCLUSION Unprotected left main coronary disease in ACS is associated with high mortality, especially in patients with STEMI and/or haemodynamic or arrhythmic instability. Percutaneous coronary intervention is now the most common revascularization strategy and preferred in higher risk patients. Coronary artery bypass graft is often delayed and performed in lower risk patients, leading to good 6-month survival. The two approaches therefore appear complementary.

Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score

Objectives Risk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices. Design and setting The GRACE risk score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005. Participants Patients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes. Outcome measures The GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors. Results For key independent risk predictors of death (1 year), non-linear associations (vs linear) were found for age (p<0.0005), systolic blood pressure (p<0.0001), pulse (p<0.0001) and creatinine (p<0.0001). By employing non-linear algorithms, there was improved model discrimination, validated externally. Using the FAST-MI 2005 cohort, the c indices for death exceeded 0.82 for the overall population at 1 year and also at 3 years. Discrimination for death or MI was slightly lower than for death alone (c=0.78). Similar results were obtained for hospital survivors, and with substitutions for creatinine and Killip class, the model performed nearly as well. Conclusions The updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.

Factors related to heart rupture in acute coronary syndromes in the Global Registry of Acute Coronary Events

AIMS To determine the incidence and factors associated with heart rupture (HR) in acute coronary syndrome (ACS) patients. METHODS AND RESULTS Among 60 198 patients, 273 (0.45%) had HR (free wall rupture, n = 118; ventricular septal rupture, n = 155). Incidence was 0.9% for ST-segment elevation myocardial infarction (STEMI), 0.17% for non-STEMI, and 0.25% for unstable angina. Hospital mortality was 58 vs. 4.5% in patients without HR (P < 0.001). The incidence was lower in STEMI patients with primary percutaneous coronary intervention (PCI) than in those without (0.7 vs. 1.1%; P = 0.01), but primary PCI was not independently related to HR in adjusted analysis (P = 0.20). Independent variables associated with HR included: ST-segment elevation (STE)/left bundle branch block; ST-segment deviation; female sex; previous stroke; positive initial cardiac biomarkers; older age; higher heart rate; systolic blood pressure/30 mmHg decrease. Conversely, previous MI and the use of low-molecular-weight heparin and beta-blockers during first 24 h were identified as protective factors for HR. CONCLUSION The incidence of HR is low in patients with ACS, although its incidence is probably underestimated. Heart rupture occurs more frequently in ACS with STE and is associated with high hospital mortality. A number of variables are independently related to HR.

Reperfusion in Patients With Renal Dysfunction After Presentation With ST-Segment Elevation or Left Bundle Branch Block: GRACE (Global Registry of Acute Coronary Events)

OBJECTIVES We investigated the relative benefit of reperfusion strategies in renal dysfunction and ST-segment elevation/left bundle branch block (STE/LBBB). BACKGROUND Few data are available informing the treatment of STE myocardial infarction in the presence of renal dysfunction. METHODS Patients (N = 12,532) from the GRACE (Global Registry of Acute Coronary Events) presenting with STE/LBBB were stratified by renal function and receipt of fibrinolysis, primary percutaneous coronary intervention (PCI), or neither. RESULTS As renal function declined, hospital mortality increased and reperfusion decreased (both p < 0.001). Compared with no reperfusion, primary PCI was associated with lower hospital mortality in patients with normal renal function (1.9% vs. 3.7%, p = 0.001, adjusted) but no reduction in those with renal dysfunction (14% vs. 15% for glomerular filtration rate [GFR] 30 to 59 ml/min/1.73 m(2); 29% vs. 32% for GFR <30 ml/min/1.73 m(2)). Fibrinolysis was not associated with lower hospital mortality for normal (3.1% vs. 3.7%, p = NS) or low renal function (32% vs. 32%, p = NS) and with higher mortality with moderate renal dysfunction (adjusted odds ratio: 1.35, 95% confidence interval: 1.01 to 1.80). Primary PCI was associated with increased hospital bleeding and fibrinolysis with increased stroke in all patients. Among hospital survivors, primary PCI, but not fibrinolysis, was associated with lower mortality for moderate dysfunction. Both reperfusion strategies were associated with higher mortality for severe dysfunction. CONCLUSIONS In STE/LBBB and renal dysfunction, mortality rates are high and reperfusion rates are lower. In moderate renal dysfunction, primary PCI is associated with mortality reduction at 6 months. Outcomes remain poor with severe renal dysfunction, despite receipt of reperfusion therapy.