Global patterns of use of antithrombotic and antiplatelet therapies in patients with acute coronary syndromes: insights from the Global Registry of Acute Coronary Events (GRACE)

Background

Many agents are available to treat acute coronary syndromes (ACS), yet limited information is available about their use from a multinational perspective. The objective of this report was to describe patterns of use of antithrombotic and antiplatelet therapies in patients with the spectrum of ACS through the use of data from the Global Registry of Acute Coronary Events (GRACE).

Methods

Data from 12,665 patients with ACS were analyzed. Baseline characteristics, clinical presentation, and medication use were compared. Regional differences in the administration of antiplatelet and antithrombotic therapies were analyzed. Multivariable logistic regression was implemented to determine independent variables indicating the use of various hospital therapies.

Results

Overall, unfractionated heparin was used in 57% of patients and low-molecular-weight heparin in 47% (P < .0001). More than 90% of patients received aspirin, but approximately 13% were not discharged on aspirin. Overall, 30% of patients received thienopyridines (with percutaneous coronary intervention [PCI] in 79%). Of those who did not receive aspirin, 31% received thienopyridines. Intravenous glycoprotein inhibitors were given to 17% of patients. Among those treated with PCI, only 47% received glycoprotein inhibitors, and 21% of those given glycoprotein inhibitors did not undergo PCI. Significant geographic variation was apparent in the use of unfractionated heparin, low-molecular-weight heparin, thienopyridines, and glycoprotein inhibitors.

Conclusions

Despite the availability of guidelines, striking geographic and practice variations are apparent in the use of antithrombotic and antiplatelet therapies. There remains significant room for improvement in the use of these therapies in patients with ACS, which should lead to improvement in care and outcomes.     

Implications of diabetes in patients with acute coronary syndromes. The Global Registry of Acute Coronary Events

BACKGROUND: There are limited data describing the presenting characteristics, management, and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome (ACS). OBJECTIVE: To examine differences in these factors, patients with ST-segment elevation acute myocardial infarction, non-ST-segment elevation acute myocardial infarction, and unstable angina were enrolled in a large multinational coronary disease registry. METHODS: The Global Registry of Acute Coronary Events is a prospective observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries. The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infarction, 4725 with non-ST-segment elevation acute myocardial infarction, and 5988 with unstable angina. RESULTS: Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes. Patients with diabetes were older, more often women, with a greater prevalence of comorbidities, and they were less likely to be treated with effective cardiac therapies than nondiabetic patients. Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure, renal failure, cardiogenic shock, and death. These differences remained after adjustment for potentially confounding prognostic factors. CONCLUSIONS: A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes. There are certain proven therapeutic strategies that remain underused in the diabetic population. A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS.     

Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE)

Objective

To examine the association between elevated leukocyte count and hospital mortality and heart failure in patients enrolled in the multinational, observational Global Registry of Acute Coronary Events (GRACE).

Background

Elevated leukocyte count is associated with adverse hospital outcomes in patients presenting with acute myocardial infarction (AMI). The association of this prognostic factor with hospital mortality and heart failure in patients with other acute coronary syndromes (ACS) is unclear.

Methods

We examined the association between admission leukocyte count and hospital mortality and heart failure in 8269 patients presenting with an ACS. This association was examined separately in patients with ST-segment elevation AMI, non-ST-segment elevation AMI, and unstable angina. Leukocyte count was divided into 4 mutually exclusive groups (Q): Q1 <6000, Q2 = 6000-9999, Q3 = 10,000-11,999, Q4 >12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events while accounting for the simultaneous effect of several potentially confounding variables.

Results

Increasing leukocyte count was significantly associated with hospital death (adjusted odds ratio [OR] 2.8, 95% CI 2.1-3.6 for Q4 compared to Q2 [normal range]) and heart failure (OR 2.7, 95% CI 2.2-3.4) for patients presenting with ACS. This association was seen in patients with ST-segment elevation AMI (OR for hospital death 3.2, 95% CI 2.1-4.7; OR for heart failure 2.4, 95% CI 1.8-3.3), non-ST-segment elevation AMI (OR for hospital death 1.9, 95% CI 1.2-3.0; OR for heart failure 1.7, 95% CI 1.1-2.5), or unstable angina (OR for hospital death 2.8, 95% CI 1.4-5.5; OR for heart failure 2.0, 95% CI 0.9-4.4).

Conclusion

In men and women of all ages with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure.     

Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE).

AIMS: There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding. METHODS AND RESULTS: Data from 24045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28). CONCLUSIONS: In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding.     

One-year outcome of patients after acute coronary syndromes (from the Canadian Acute Coronary Syndromes Registry)

The objective of this study was to determine the management and outcome of fewer selected patients with an acute coronary syndrome during hospitalization and up to 1 year after discharge. The Canadian Acute Coronary Syndromes Registry was a prospective observational study of patients admitted with suspected acute coronary syndromes. Data on demographic and clinical characteristics, in-hospital treatment, and outcomes were recorded. At 1 year, vital status, medication use, recurrent cardiac events, and procedures were determined by telephone contact. Of the 5,312 patients enrolled, 4,627 had a final diagnosis of acute coronary syndrome, with Q-wave myocardial infarction in 27.7%, non-Q-wave myocardial infarction in 33.2%, and unstable angina pectoris in 39.1%. During hospitalization, coronary angiography and revascularization were performed in 39.6% and 20.3% of patients, respectively. The in-hospital mortality rate was 2.4% overall. At discharge, 87.8%, 76.4%, 56.0%, and 54.8% of patients were prescribed aspirin, β blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering agents, respectively. Unadjusted 1-year mortality rates for hospital survivors were 6.5%, 10%, and 5.4% for those with Q-wave myocardial infarction, non-Q-wave myocardial infarction, and unstable angina pectoris groups, respectively (p <0.0001). This difference in mortality rate remained significant after adjusting for other prognosticators, whereas the use of coronary angiography and revascularization after discharge was similar across patients. At 1 year, fewer patients were maintained on aspirin and β blockers, whereas the use of lipid-lowering therapy increased (all p <0.0001). Despite similar rates of coronary angiography and revascularization after discharge, patients with non-Q-wave myocardial infarction had worse outcomes at 1 year. Moreover, there was a significant opportunity to enhance the discharge and long-term use of evidence-based secondary prevention therapies.     

Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE])

The long-term use of aspirin (ASA) reduces the risk of subsequent acute coronary syndromes in patients with coronary artery disease (CAD). It is less clear whether ASA therapy benefits patients who develop an acute coronary syndrome despite its use. Baseline characteristics, type of acute coronary syndrome, and in-hospital events were compared on the basis of previous use of ASA in 11,388 patients with and without a history of CAD presenting to 94 multinational hospitals. A total of 73.0% of patients with a history of CAD (n = 4,974) were previously on long-term ASA therapy compared with 19.4% of patients without a history of CAD (n = 6,414). After multivariate regression analysis controlling for various potentially confounding factors, patients with a history of CAD who were previously taking ASA were significantly less likely to present with ST-segment elevation myocardial infarction (MI) (adjusted odds ratio [OR] 0.52, 95% confidence intervals [CI] 0.44 to 0.61) or die during hospitalization (OR 0.69, 95% CI 0.50 to 0.95) in comparison to patients who were not taking ASA. Patients without a history of CAD and who were previously taking ASA also had a lower risk of developing ST-segment elevation MI (OR 0.35, 95% CI 0.30 to 0.40) and a trend toward a decreased hospital death rate (OR 0.77, 95% CI 0.55 to 1.07). These results demonstrate that patients with a history of CAD who present with an acute coronary syndrome despite prior ASA use have less severe clinical presentation, fewer hospital complications, and lower in-hospital death rates than patients not previously taking ASA.     

Management of acute coronary syndromes. Variations in practice and outcome; findings from the Global Registry of Acute Coronary Events (GRACE).

AIMS: Despite advances in the treatment of acute coronary syndromes based on randomized trial data and published guidelines, the extent to which such treatments are applied in practice remains uncertain. Data from clinical trials derive from selected geographical areas and in highly selected populations of patients, and hence may not reflect the overall population. The aim of the study was to investigate variations in hospital management and outcome using unselected data collected in the prospective Global Registry of Acute Coronary Events (GRACE). METHODS AND RESULTS: The 95 hospitals in GRACE were organized into 18 population-based clusters in 14 countries. Information was recorded about patient management and outcome during hospitalization and after discharge. Data on treatments administered were analysed by baseline condition, hospital type, by the presence or absence of a catheterization laboratory, and by geographical region. Of 11543 patients, 44% had an admission diagnosis of unstable angina, 36% presented with myocardial infarction, 9% were admitted to rule out a myocardial infarction, 7% had chest pain and 4% were hospitalized for 'other cardiac' and 'non-cardiac' diagnoses. Of the total GRACE population 38% had a final diagnosis of unstable angina, 30% ST-segment elevation myocardial infarction, 25% non-ST-segment elevation myocardial infarction, and 7% of 'other cardiac' and 'non-cardiac' final diagnoses. The event rates for hospital death or reinfarction were six and 2% for non-ST-segment elevation myocardial infarction, seven and 3% for ST-segment elevation myocardial infarction, and 3% hospital death for unstable angina. The use of aspirin was similar across all hospital types and geographical regions. In contrast, the use of percutaneous coronary intervention and glycoprotein IIb/IIIa inhibitors was higher (P<0.0001) in teaching hospitals and hospitals with catheterization laboratories and was also higher in the United States. At discharge a higher percentage (P<0.0001) of patients received angiotensin-converting enzyme inhibitors in hospitals without catheterization laboratories. The use of statins was lower in non-teaching hospitals and in centres without a catheterization laboratory. CONCLUSIONS: The GRACE study reveals substantial differences in the management of patients based on hospital type and geographical location. Further analyses will determine whether such variations translate into differences in longer term outcomes. GRACE provides a multinational reference for the implementation of therapies of proven efficacy.     

Comparison of acute coronary syndrome in patients receiving versus not receiving chronic dialysis (from the Global Registry of Acute Coronary Events [GRACE] Registry)

Patients with end-stage renal disease commonly develop acute coronary syndromes (ACS). Little is known about the natural history of ACS in patients receiving dialysis. We evaluated the presentation, management, and outcomes of patients with ACS who were receiving dialysis before presentation for an ACS and were enrolled in the Global Registry of Acute Coronary Events (GRACE) at 123 hospitals in 14 countries from 1999 to 2007. Of 55,189 patients, 579 were required dialysis at presentation. Non-ST-segment elevation myocardial infarction was the most common ACS presentation in patients receiving dialysis, occurring in 50% (290 of 579) of patients versus 33% (17,955 of 54,610) of those not receiving dialysis. Patients receiving dialysis had greater in-hospital mortality rates (12% vs 4.8%; p <0.0001) and, among those who survived to discharge, greater 6-month mortality rates (13% vs 4.2%; p <0.0001), recurrent myocardial infarction (7.6% vs 2.9%; p <0.0001), and unplanned rehospitalization (31% vs 18%; p <0.0001). The outcome in patients receiving dialysis was worse than that predicted by their calculated GRACE risk score for in-hospital mortality (7.8% predicted vs 12% observed; p <0.05), 6-month mortality/myocardial infarction (10% predicted vs 21% observed; p <0.05). In conclusion, in the present large multinational study, approximately 1% of patients with ACS were receiving dialysis. They were more likely to present with non-ST-segment elevation myocardial infarction, and had markedly greater in-hospital and 6-month mortality. The GRACE risk score underestimated the risk of major events in patients receiving dialysis.     

Impact of prior peripheral arterial disease and stroke on outcomes of acute coronary syndromes and effect of evidence-based therapies (from the Global Registry of Acute Coronary Events)

We assessed the effect of previous peripheral arterial disease (PAD) and stroke on clinical outcomes in patients with acute coronary syndrome (ACS) and sought to ascertain the effectiveness of evidence-based therapies in these patients. We used data from the multinational Global Registry of Acute Coronary Events. Patients were enrolled at 102 hospitals in 13 countries between April 1999 and September 2005. Patients presenting with ACS were stratified according to the presence of previous PAD, stroke, PAD and stroke, or neither. In-hospital analysis included 48,418 patients and 6-month analysis included 32,735 patients. The primary end point was all-cause mortality and major adverse cardiac events during 6-month follow-up. Adverse in-hospital and 6-month events were lowest in patients with neither PAD nor stroke and highest in patients with PAD and stroke after adjustment for baseline demographics and co-morbidities. In-hospital mortality for the 4 groups (neither, PAD, stroke, PAD and stroke) was 4.5% versus 7.2% versus 8.9% versus 9.4% (p <0.001) and that for 6-month mortality was 3.9% versus 8.8% versus 9.3% versus 12%, and these differences persisted after accounting for differences in baseline characteristics. Use of evidence-based therapies was associated with significantly less morbidity and mortality in all ACS subgroups. In conclusion, outcomes after ACS are worse in patients with PAD or stroke, with the highest risk in patients with the 2 conditions and the use of evidence-based therapies are associated with improved outcomes in all ACS subgroups.