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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)
General Cardiology
Methods: Consecutive patients (n⫽448, mean [⫾SD] age, 60⫾12 years) with acute myocardial infarction had their serum C-reactive protein levels measured within 12–24 hours of symptom onset and were divided into tertiles. Infarct size (by echocardiographic examination performed on day 2 or 3) and mortality at 30 days and subsequent cardiac events were determined for these tertiles. Results: Mortality at 30 days was higher with increasing C-reactive protein tertile (3%, 10% and 22% in low-, middle- and high-risk tertiles; p⫽0.02 for middle vs. lowest tertile and p⬍0.001 for highest vs. lowest tertile). Multivariate analysis identified C-reactive protein in the upper tertile as an independent-predictor of 30-day mortality (relative risk⫽3.0; 95% confidence interval [CI]: 1.3–7.2; p⫽0.01) and the development of heart failure (odds ratio⫽2.6; 95% CI: 1.5– 4.6; p⫽0.0006). In contrast, C-reactive protein levels were not associated with the development of postinfarction angina, recurrent myocardial infarction or the need for revascularization. Conclusion: Plasma C-reactive protein level obtained within 12–24 hours of symptoms onset is an independent marker of 30-day mortality and the development of heart failure in patients with acute myocardial infarction. Perspective: C-reactive protein, a marker of inflammation, appears to predict not only 30-day mortality but also the development of heart failure, suggesting a potential role of inflammation in left ventricular remodeling after acute myocardial infarction. RM
Abstracts Women’s Early Warning Symptoms of Acute Myocardial Infarction McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Barvin BJ. Circulation 2003;108:2619 –23. Study Question: What are the prodromal signs and symptoms of acute myocardial infarction in women? Methods: Women diagnosed with AMI from five sites (n⫽515) were surveyed 4 – 6 months after discharge using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey. This survey included a questionnaire with regards to their symptoms, comorbidities and demographic characteristics. Results: Women in this cohort were predominantly white (93%), high school educated (54.8%) and older (mean age, 66⫾12). Prodromal symptoms were reported in 95% of women with the most frequent prodromal symptoms experienced more than 1 month before AMI being unusual fatigue (70.7%), sleep disturbance (47.8%) and shortness of breath (42.1%). Chest discomfort was reported in only 29.7% more than a month before their AMI. The most frequent acute symptoms included shortness of breath (57.9%), weakness (54.8%), and fatigue (42.9%) with chest discomfort reported by only 43% of patients. Women had more acute (mean, 7.3⫾4.8; range, 0 –29) than prodromal (mean, 5.71⫾4.36; range, 0 –25) symptoms. These two scores were correlated (r⫽0.61, p⬍0.001). Women with more prodromal symptoms experienced more acute symptoms. After controlling for risk factors, prodromal scores accounted for 33.2% of acute symptomatology. Conclusions: Most women have prodromal symptoms before AMI, but it is unknown whether prodromal symptoms are predictive of future events. Perspective: It is important to recognize that atypical presentation of AMI with shortness of breath, extreme fatigue and weakness, rather than typical chest discomfort, is not uncommon in women. The lack of healthy controls in this study makes it difficult to attribute the vague symptoms described a month before their AMI to be indicative of a future acute event, which is usually related to sudden plaque rupture. RM
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) Budaj A, Brieger D, Steg G, et al. Am Heart J 2003;146:999 – 1006. Study Question: What are the patterns of use of antithrombotic and antiplatelet therapies across the globe in patients with the spectrum of acute coronary syndromes (ACS)? Methods: Patients with ACS (n⫽12,665) enrolled in the Global Registry of Acute Coronary Events (GRACE) had their data analyzed. Baseline characteristics, clinical presentation and medication use were compared in the different types of ACS, and regional differences in the use of antiplatelet and antithrombotic therapies were evaluated. Multivariable logistic regression was implemented to determine independent variables indicating the use of various hospital therapies. Results: The use of unfractionated heparin was higher than that for low–molecular-weight heparin (57% vs. 47%, p⬍0.0001). More than 90% of patients received aspirin in hospital, 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 thien-
Admission C-Reactive Protein Levels and 30-Day Mortality in Patients With Acute Myocardial Infarction Suleiman M, Aronson D, Reisner SA, et al. Am J Med 2003;115: 695–701. Study Question: What is the value of C-reactive protein levels in predicting the risk of subsequent cardiovascular events in patients with acute myocardial infarction?
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Conclusions: In patients with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure. Perspective: This and many prior studies have demonstrated the importance of elevated leukocyte count and other inflammatory markers (i.e., C-reactive protein, cytokines, myeloperoxidases) in determining the long-term prognosis after an acute coronary event supporting a major role of inflammation in acute coronary syndromes. RM
opyridines. 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 antithrombotic and antiplatelet therapies with unfractionated and low–molecular-weight heparin being more commonly utilized in patients with ACS outside United States and thienopyridines, and glycoprotein inhibitors being used less commonly in those outside United States. Conclusions: Striking geographic and practice variations are apparent in the use of antithrombotic and antiplatelet therapies around the world. Perspective: This study highlights the significant challenge of guideline implementation globally for patients with ACS. Many of the differences seen are fueled by local or regional financial pressures either favoring or not favoring a given treatment. RM
Benefits of Statin Treatment in Cardiac Syndrome-X Kayikcioglu M, Pazin S, Yavuzgil O, Kultursay H, Can LH, Soydan I. Eur Heart J 2003;24:1999 –2005. Study Question: Syndrome-X or angina with normal epicardial coronary arteries is associated with arterial endothelial dysfunction and abnormalities in the coronary microcirculation. Do statins benefit endothelial function in syndrome-X and is this associated with less exercise-induced ischemia? Methods: 40 patients with syndrome-X were randomized in a single-blind fashion to 3 months of pravastatin 40 mg/day or placebo regardless of lipid parameters. Diagnostic criteria for syndrome-X included typical exercise induced angina, ⬎1 mm ST depression with exercise and angiographically normal coronary arteries. Arterial endothelial function was determined at baseline and after treatment as brachial artery flow mediated dilation (FMD) measured by ultrasound. Medications were withdrawn at least 1 week prior to the study. Sublingual nitroglycerin was permitted until 24 hours prior to the procedures. Results: Average age was 46 years, 55% were female, 35% smokers, mean BP 110/72 mm Hg, total cholesterol 193 mg/dL, LDL-C 121 mg/dL, HDL 44 mg/dL, peak exercise work 10.8 METs, time to 1 mm ST depression 249 seconds, and FMD 9.3⫾8%, with no difference in these variables between groups at baseline. After 3 months, pravastatin lowered the LDL-C by 17% with no change by placebo. Pravastatin therapy increased FMD (9.7⫾8.6% to 16.3⫾6.8%) and exercise duration and time from 1 mm ST depression with no change on placebo. The change in FMD correlated relatively highly with exercise duration (r⫽⫺0.647, p⫽0.04). Ischemic symptoms and exercise ECG findings resolved in 26% of the pravastatin group and there was a significant improvement in angina class compared to placebo. There were no changes in FMD or exercise parameters in the placebo group. Conclusions: Statin therapy resulted in beneficial effects on both exercise induced ischemia and FMD in cardiac Syndrome X, probably related to improved arterial endothelial function. Perspective: Syndrome-X is often associated with increased lipids and smoking as in this study, and IVUS often shows epicardial non-occlusive plaque not appreciated on coronary angiography. Statins and L-arginine have both been shown to enhance endothelial function in syndrome-X. The
Elevated Leukocyte Count and Adverse Hospital Events in Patients With Acute Coronary Syndromes: Findings From the Global Registry of Acute Coronary Events (GRACE) Furman MI, Gore JM, Anderson FA, et al. Am Heart J 2004;147: 42– 8. Study Question: Was there an 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)? Methods: The association between admission leukocyte count and hospital mortality and heart failure was examined in 8269 patients presenting with an acute coronary syndrome (ACS). This association was examined separately in patients with ST-segment elevation AMI, non–ST-segment elevation AMI and unstable angina. Patients were categorized based on their leukocyte count into four mutually exclusive groups (Q): Q1⬍6000, Q2⫽6000 –9999, Q3⫽10,000 –11,999, Q4ⱖ12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events adjusting 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).
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Methods: Consecutive patients (n⫽448, mean [⫾SD] age, 60⫾12 years) with acute myocardial infarction had their serum C-reactive protein levels measured within 12–24 hours of symptom onset and were divided into tertiles. Infarct size (by echocardiographic examination performed on day 2 or 3) and mortality at 30 days and subsequent cardiac events were determined for these tertiles. Results: Mortality at 30 days was higher with increasing C-reactive protein tertile (3%, 10% and 22% in low-, middle- and high-risk tertiles; p⫽0.02 for middle vs. lowest tertile and p⬍0.001 for highest vs. lowest tertile). Multivariate analysis identified C-reactive protein in the upper tertile as an independent-predictor of 30-day mortality (relative risk⫽3.0; 95% confidence interval [CI]: 1.3–7.2; p⫽0.01) and the development of heart failure (odds ratio⫽2.6; 95% CI: 1.5– 4.6; p⫽0.0006). In contrast, C-reactive protein levels were not associated with the development of postinfarction angina, recurrent myocardial infarction or the need for revascularization. Conclusion: Plasma C-reactive protein level obtained within 12–24 hours of symptoms onset is an independent marker of 30-day mortality and the development of heart failure in patients with acute myocardial infarction. Perspective: C-reactive protein, a marker of inflammation, appears to predict not only 30-day mortality but also the development of heart failure, suggesting a potential role of inflammation in left ventricular remodeling after acute myocardial infarction. RM
Abstracts Women’s Early Warning Symptoms of Acute Myocardial Infarction McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Barvin BJ. Circulation 2003;108:2619 –23. Study Question: What are the prodromal signs and symptoms of acute myocardial infarction in women? Methods: Women diagnosed with AMI from five sites (n⫽515) were surveyed 4 – 6 months after discharge using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey. This survey included a questionnaire with regards to their symptoms, comorbidities and demographic characteristics. Results: Women in this cohort were predominantly white (93%), high school educated (54.8%) and older (mean age, 66⫾12). Prodromal symptoms were reported in 95% of women with the most frequent prodromal symptoms experienced more than 1 month before AMI being unusual fatigue (70.7%), sleep disturbance (47.8%) and shortness of breath (42.1%). Chest discomfort was reported in only 29.7% more than a month before their AMI. The most frequent acute symptoms included shortness of breath (57.9%), weakness (54.8%), and fatigue (42.9%) with chest discomfort reported by only 43% of patients. Women had more acute (mean, 7.3⫾4.8; range, 0 –29) than prodromal (mean, 5.71⫾4.36; range, 0 –25) symptoms. These two scores were correlated (r⫽0.61, p⬍0.001). Women with more prodromal symptoms experienced more acute symptoms. After controlling for risk factors, prodromal scores accounted for 33.2% of acute symptomatology. Conclusions: Most women have prodromal symptoms before AMI, but it is unknown whether prodromal symptoms are predictive of future events. Perspective: It is important to recognize that atypical presentation of AMI with shortness of breath, extreme fatigue and weakness, rather than typical chest discomfort, is not uncommon in women. The lack of healthy controls in this study makes it difficult to attribute the vague symptoms described a month before their AMI to be indicative of a future acute event, which is usually related to sudden plaque rupture. RM
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) Budaj A, Brieger D, Steg G, et al. Am Heart J 2003;146:999 – 1006. Study Question: What are the patterns of use of antithrombotic and antiplatelet therapies across the globe in patients with the spectrum of acute coronary syndromes (ACS)? Methods: Patients with ACS (n⫽12,665) enrolled in the Global Registry of Acute Coronary Events (GRACE) had their data analyzed. Baseline characteristics, clinical presentation and medication use were compared in the different types of ACS, and regional differences in the use of antiplatelet and antithrombotic therapies were evaluated. Multivariable logistic regression was implemented to determine independent variables indicating the use of various hospital therapies. Results: The use of unfractionated heparin was higher than that for low–molecular-weight heparin (57% vs. 47%, p⬍0.0001). More than 90% of patients received aspirin in hospital, 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 thien-
Admission C-Reactive Protein Levels and 30-Day Mortality in Patients With Acute Myocardial Infarction Suleiman M, Aronson D, Reisner SA, et al. Am J Med 2003;115: 695–701. Study Question: What is the value of C-reactive protein levels in predicting the risk of subsequent cardiovascular events in patients with acute myocardial infarction?
ACC CURRENT JOURNAL REVIEW Mar 2004
9
Conclusions: In patients with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure. Perspective: This and many prior studies have demonstrated the importance of elevated leukocyte count and other inflammatory markers (i.e., C-reactive protein, cytokines, myeloperoxidases) in determining the long-term prognosis after an acute coronary event supporting a major role of inflammation in acute coronary syndromes. RM
opyridines. 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 antithrombotic and antiplatelet therapies with unfractionated and low–molecular-weight heparin being more commonly utilized in patients with ACS outside United States and thienopyridines, and glycoprotein inhibitors being used less commonly in those outside United States. Conclusions: Striking geographic and practice variations are apparent in the use of antithrombotic and antiplatelet therapies around the world. Perspective: This study highlights the significant challenge of guideline implementation globally for patients with ACS. Many of the differences seen are fueled by local or regional financial pressures either favoring or not favoring a given treatment. RM
Benefits of Statin Treatment in Cardiac Syndrome-X Kayikcioglu M, Pazin S, Yavuzgil O, Kultursay H, Can LH, Soydan I. Eur Heart J 2003;24:1999 –2005. Study Question: Syndrome-X or angina with normal epicardial coronary arteries is associated with arterial endothelial dysfunction and abnormalities in the coronary microcirculation. Do statins benefit endothelial function in syndrome-X and is this associated with less exercise-induced ischemia? Methods: 40 patients with syndrome-X were randomized in a single-blind fashion to 3 months of pravastatin 40 mg/day or placebo regardless of lipid parameters. Diagnostic criteria for syndrome-X included typical exercise induced angina, ⬎1 mm ST depression with exercise and angiographically normal coronary arteries. Arterial endothelial function was determined at baseline and after treatment as brachial artery flow mediated dilation (FMD) measured by ultrasound. Medications were withdrawn at least 1 week prior to the study. Sublingual nitroglycerin was permitted until 24 hours prior to the procedures. Results: Average age was 46 years, 55% were female, 35% smokers, mean BP 110/72 mm Hg, total cholesterol 193 mg/dL, LDL-C 121 mg/dL, HDL 44 mg/dL, peak exercise work 10.8 METs, time to 1 mm ST depression 249 seconds, and FMD 9.3⫾8%, with no difference in these variables between groups at baseline. After 3 months, pravastatin lowered the LDL-C by 17% with no change by placebo. Pravastatin therapy increased FMD (9.7⫾8.6% to 16.3⫾6.8%) and exercise duration and time from 1 mm ST depression with no change on placebo. The change in FMD correlated relatively highly with exercise duration (r⫽⫺0.647, p⫽0.04). Ischemic symptoms and exercise ECG findings resolved in 26% of the pravastatin group and there was a significant improvement in angina class compared to placebo. There were no changes in FMD or exercise parameters in the placebo group. Conclusions: Statin therapy resulted in beneficial effects on both exercise induced ischemia and FMD in cardiac Syndrome X, probably related to improved arterial endothelial function. Perspective: Syndrome-X is often associated with increased lipids and smoking as in this study, and IVUS often shows epicardial non-occlusive plaque not appreciated on coronary angiography. Statins and L-arginine have both been shown to enhance endothelial function in syndrome-X. The
Elevated Leukocyte Count and Adverse Hospital Events in Patients With Acute Coronary Syndromes: Findings From the Global Registry of Acute Coronary Events (GRACE) Furman MI, Gore JM, Anderson FA, et al. Am Heart J 2004;147: 42– 8. Study Question: Was there an 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)? Methods: The association between admission leukocyte count and hospital mortality and heart failure was examined in 8269 patients presenting with an acute coronary syndrome (ACS). This association was examined separately in patients with ST-segment elevation AMI, non–ST-segment elevation AMI and unstable angina. Patients were categorized based on their leukocyte count into four mutually exclusive groups (Q): Q1⬍6000, Q2⫽6000 –9999, Q3⫽10,000 –11,999, Q4ⱖ12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events adjusting 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).
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