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Myocardial Ischemia and Infarction
Journal of the American College of Cardiology © 2005 by the American College of Cardiology Foundation Published by Elsevier Inc.
Vol. 45, No. 11 Suppl B ISSN 0735-1097/05/$30.00 doi:10.1016/j.jacc.2005.05.011
Myocardial Ischemia and Infarction John W. Hirshfeld, JR, MD, FACC Philadelphia, Pennsylvania A total of 828 abstracts were submitted in the various myocardial ischemia and infarction categories. Of these, 297 were accepted for presentation. The presented abstracts may be grouped into seven topical categories. 1. Prevention of coronary heart disease (CHD) 2. Risk prediction for CHD 3. Pharmacologic treatment for ST-segment elevation myocardial infarction (STEMI) 4. Reperfusion treatment for STEMI 5. Advances in cell therapy for CHD 6. Quality management and improvement in myocardial infarction (MI) 7. Miscellaneous topics This article summarizes the most significant presentations.
PREVENTION OF CHD Role of aspirin and vitamin E in preventing coronary events in women. Paul Ridker and Stacy Buring presented the results of the Women’s Health Study Research Group randomized trial of primary prevention of CHD in 39,876 initially healthy female health professionals age ⬎45 years (1). Subjects were randomized in a double factorial randomization scheme to 100 mg of aspirin every other day versus placebo and 600 mg vitamin E every other day versus placebo. Follow-up was 10.1 years. The end points were cardiovascular mortality, nonfatal MI, and nonfatal stroke. The aspirin arm of the trial was positive and the vitamin E arm was negative. Because this was a very healthy population, the overall end point event rate was small at 2.5% over a 10-year observation period. Aspirin reduced the end point event rate by 9%, which was not statistically significant (p ⫽ 0.13). The reduction was leveraged by a significant reduction in the rate of ischemic stroke (relative risk ⫽ 0.76; p ⫽ 0.009). There was no effect on all-cause mortality or cardiovascular death. This study demonstrates a modest protective effect of aspirin, even in a low-risk population, and confirms the lack of effectiveness of vitamin E. Blood pressure (BP)-lowering strategy revisited. Peter Sever presented the findings of the (Anglo-Scandanavian Cardiac Outcomes Trial (ASCOT) blood pressurelowering arm (2). This trial compared two different pharmacologic strategies for lowering BP (amlodipine ⫾ perindopril vs. atenolol ⫾ benzoflumethazide) in 19,257 hypertensive men and women. The protocol treated patients to a BP ⬍140/90 mm Hg for non-diabetics and 130/80 mm Hg for diabetics. Amlodipine or atenolol were started From the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
initially and perindopril or benzoflumethazide were added if target BP was not achieved with a single drug. Follow-up was 5.1 years. End points were cardiovascular mortality and nonfatal MI. The majority of patients required both drugs to achieve target BP. The trial was stopped prematurely by the safety committee because of the emergence of superiority in the amlodipine/perindopril group. The primary end point was reduced by 10% from 4.6% to 4.1%. Other multiple cardiovascular end points were reduced in the amlodipine/perindopril group (stroke 30%, all coronary events 13%, all cardiovascular events and procedures 16%, cardiovascular mortality 16%). The trial demonstrates the superiority of the amlodipine/perindopril strategy. The difference between the strategies was not due to differences in BP because both groups achieved the same target BP levels. Thus, the difference must be due to the different drug classes used. Because the majority of patients received both drugs, one cannot determine whether one of the drugs in the trial arm pair was predominantly responsible for the difference. Aggressive low-density lipoprotein (LDL) lowering. John LaRosa presented the results of the Treating to New Targets (TNT) trial. Patients with clinically evident coronary disease were enrolled (n ⫽ 10,002) (3). Eligibility required that subjects achieve an LDL below 130 mg/dl on 10 mg of atorvastatin. Eligible subjects were then randomized between continuing 10 mg of atorvastatin and advancing to 80 mg of atorvastatin. Patients were followed until the design-required number of end point events (cardiovascular mortality, nonfatal MI, resuscitated cardiac arrest, or stroke) had been accumulated (five years). The 10 mg atorvastatin group achieved a mean LDL of 100 mg/dl, whereas the mean LDL for the 80 mg atorvastatin group was 80 mg/dl. The frequency of end point events was reduced in the 80 mg atorvastatin group (10.0% vs. 12.2%; p ⫽ 0.002). There was no difference between the two groups in the frequency of statin-related side effects. This study validates the concept that, with LDL cholesterol, lower is better.
CHD RISK PREDICTION Two studies were presented that endeavored to refine the ability to predict future coronary risk. Multimarker approach to risk prediction. Christopher Arant, representing the Women’s Ischemia Syndrome Evaluation (WISE) team, investigated a high-risk population of 595 women who were being evaluated for suspected myocardial ischemia (4). The population had a high prevalence of traditional coronary risk factors. They were further risk
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stratified by markers of inflammation— high-sensitivity C-reactive protein (hs-CRP), interleukin-6, and serum amyloid antigen. The women were followed for a mean of 3.6 years with end points of all-cause death, hospitalization for MI, congestive heart failure, stroke, or other vascular events. The annual risk of an end point event increased progressively if two or more abnormal markers were present (0 or 1 marker ⫽ 1.90%; 2 ⫽ 3.68%; 3 ⫽ 5.5%). These findings are consistent with the importance of inflammatory markers as predictors of vascular risk independently of other risk factors. Inflammation and hyperglycemia. Kausik K. Ray, representing the Thrombolysis In Myocardial Infarction (TIMI) investigators, conducted a pooled analysis of the patients enrolled in four TIMI trials (5). Patients with acute coronary syndromes were categorized by the presence or absence of diabetes, and within diabetics, by tertiles of glucose level. Patients were also characterized by levels of hs-CRP. Diabetic patients, as a group, had higher levels of hs-CRP than non-diabetics. End points were death or MI over 10 months. Both diabetes and hs-CRP were predictive of events, with diabetes being the stronger predictor. Nondiabetics with low hs-CRP levels had an 18% event rate compared with 33% for diabetics with elevated hs-CRP levels. The worst outcomes were in diabetics with elevated hs-CRP levels whose random glucose was in the top tertile. This study demonstrates, once again, that diabetes is a powerful adverse risk factor and the hs-CRP level adds independent incremental risk prediction.
PHARMACOLOGIC TREATMENT OF STEMI Studies of both classical as well as novel therapeutic approaches to the treatment of STEMI were presented. The classical approaches involved refinements of antiplatelet and beta-blocker therapy. The novel approaches examined an old and a new treatment strategy. Clopidogrel was studied in two randomized STEMI trials, both of which demonstrated benefit for adjunctive concomitant clopidogrel therapy at the time of presentation with STEMI. Clopidogrel as an adjunct to thrombolysis. Marc Sabatine, representing the TIMI-28 study group, presented the results of the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) trial (6). This trial randomized 3,496 patients who had undergone intravenous fibrinolysis for STEMI to an antiplatelet regimen of aspirin alone compared with aspirin plus a 300-mg load of clopidogrel followed by a daily dose of 75 mg. Patients subsequently underwent angiography at a median of 3.5 days after fibrinolysis. Efficacy end points included death, recurrent MI, or an occluded infarct artery. The safety end point was TIMI major bleeding. The primary end point through the time of angiography was reduced from 21.7% to 15.0% (odds ratio 0.64; p ⬍ 0.001) and was leveraged predomi-
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nantly by greater infarct artery patency at the time of elective angiography. The frequency of TIMI major bleeding was similar in both treatment groups, although TIMI minor bleeding was slightly, but not statistically, significantly increased (1.0% vs. 0.5%; p ⫽ 0.17) in the clopidogrel group. This study demonstrated a benefit of clopidogrel therapy in patients who do not receive prompt invasive evaluation and treatment. Clopidogrel as an adjunct to aspirin. Clopidogrel was also studied as an adjunct to standard therapy with aspirin in patients with STEMI who mostly did not receive subsequent invasive therapy (7). Zhenming Chen reported the results of the Clopidogrel and Metoprolol in Myocardial Infarction (COMMIT/CCS2) study, which enrolled 46,000 patients presenting with STEMI at 1,250 hospitals in China. The patients were randomized to receive aspirin alone or aspirin plus 75 mg of clopidogrel per day (no loading dose) for 30 days. Fifty-two percent of the patients received thrombolytic therapy. The end point was a composite of death, nonfatal re-infarction, and stroke. The clopidogrel group had a 9% reduction in the end point (9.3% vs. 10.1%; p ⫽ 0.002) at 30 days. The primary end point difference was driven mainly by a reduction in mortality (7.3% vs. 8.1%; p ⫽ 0.03). Upstream administration of abciximab. Jochen Goedicke presented a meta-analysis of six clinical trials of primary percutaneous coronary intervention (PCI) for STEMI comparing the outcomes of patients who received abciximab before angiography (upstream) compared with receiving it at the time of PCI (8). The primary end point was a composite of death, re-infarction, and target vessel revascularization at 30 days. Upstream abciximab patients received the drug an average of 50 min before PCI compared with 5 min in the non-upstream group. Infarct artery patency at the time of angiography was greater in the upstream group (43% vs. 29%; p ⫽ 0.001). This resulted in a nonstatistically significant decrease in the frequency of the composite end point (7.3% vs. 9.7%) and a non-statistically significant decrease in the frequency of death (2.7% vs. 4.7%). There was no difference in the frequency of major bleeding (3.5% vs. 3.8%). This study indicates that upstream administration of abciximab appears to improve outcomes in primary PCI for STEMI. Early administration of metoprolol. The COMMIT/ CCS2 trial was a two-armed multifactorial design trial. The second arm was a randomization to metoprolol versus placebo (9). Patients with STEMI who were randomized to metoprolol therapy received three 5-mg intravenous boluses of metoprolol followed by a daily oral dose of 200 mg for 30 days. The end point events were the same as in the clopidogrel arm of the trial. The results of this trial were more complex to interpret. Overall, there was no effect on mortality (metoprolol 7.7% vs. placebo 7.8%). However, metoprolol reduced the frequency of ventricular fibrillation (2.5% vs. 3.9%). There was an increased mortality in patients who presented with hemodynamic instability that
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offset a trend toward improved mortality in nonhemodynamically compromised patients. The conclusion from the trial was that metoprolol appeared to be beneficial in patients without hemodynamic compromise, but that it was likely detrimental to compromised patients. Glucose-insulin-potassium (GIK) revisited. There has been a 30-year controversy over whether administration of a GIK solution is beneficial in the early phases of STEMI. The Glucose Insulin Potassium Study (GIPS I) had suggested a possible benefit of high-dose GIK in Killip class I patients. Jorik Timmer presented the results of the GIPS II trial, which was confined to high-dose GIK in Killip class I STEMI patients (10). End points were death at 30 days, enzymatic infarct size, and left ventricular (LV) function. The trial was stopped early by the Data Safety and Monitoring Committee because of lack of effect on enzymatic infarct size and a non-significant trend toward increased mortality (2.9% vs. 1.8%; p ⫽ 0.26) in the GIK treatment group. Thus, the findings of the GIPS I trial were not confirmed and there seems to be little rationale for GIK therapy for STEMI. Matrix metalloproteinase (MMP) inhibition. W. Douglas Weaver presented a randomized trial assessing the efficacy of acute treatment with PG116800, a MMP inhibitor, with the goal to prevent ventricular remodeling after STEMI (11). The trial enrolled 253 patients undergoing primary PCI for STEMI. The population had major MIs (80% anterior, LV ejection fraction 15% to 40%). End points were a change in LV ejection fraction, a change in serum pro-brain natriuretic peptide, a change in hs-CRP, and a composite clinical end point of new or worsening congestive heart failure, hospitalization for congestive heart failure, or death. Analysis of the data revealed no detectable effect of the treatment, indicating that MMP inhibition does not appear to affect remodeling or outcome after STEMI.
REPERFUSION TREATMENT OF STEMI Many studies assessing refinement of reperfusion treatment for STEMI were presented. The predominant theme was to re-evaluate the 90-min door-to-balloon time standard. Does a 90-min door-to-balloon time matter? William W. O’Neill presented the results of a pooled analysis of four trials of PCI for STEMI (Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Debris [EMERALD], COOL MI feasibility trial [COOL], Acute Myocardial Infarction HyperOxemia Trial [AMI-HOT], Intravascular Cooling Adjunctive to Primary Coronary Intervention [ICE-IT]) (12). A total of 1,355 patients were available for analysis and were stratified by symptom onsetto-door time and door-to-balloon time. Outcome variables were death at 30 days, major cardiac adverse events at 30 days, and infarct size by sestamibi imaging. Both symptom onset-to-balloon time (p ⫽ 0.025) and door-to-balloon time (p ⬍ 0.0001) were independently associated with death
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at 30 days. Each outcome variable showed a graded relationship with door-to-balloon time up to 90 min, after which the relationship appeared to flatten. Interhospital transfer delay and mortality of STEMI. Giuseppe DeLuca examined outcomes in 616 patients who were transferred to a single hospital for primary PCI for STEMI (13). The institution’s mean door-to-balloon time was 38 min. Patients were stratified by the time delay between arrival at the first hospital and arrival at the referral hospital. End points were death at one year, myocardial blush grade, and serum lactate dehydrogenase (LDH) at 48 h after the PCI. Statistically significant associations were found for LDH at 24 h (p ⫽ 0.049) and death at 1 year (p ⫽ 0.01). There was a strong trend toward improving myocardial blush grade with shorter delay times. The association with death was particularly strong (⬍30 min ⫽ 3.2%; 30 to 59 min ⫽ 6.4%; 60 to 89 min ⫽ 6.2%; ⱖ90 min ⫽ 12.1%). Both the previously cited studies strongly reaffirm the importance of minimizing time to reperfusion in the management of STEMI. Two other studies examined the National Registry of Myocardial Infarction (NRMI) to focus on strategies to shorten door-to-balloon time. Door-to-balloon time: where can we improve? Elizabeth Bradley presented an analysis of 13,387 patients from the NRMI registry who received PCI for STEMI at 340 participating hospitals (14). Hospitals were separated into two groups: median door-to-balloon time ⬍90 min and median door-to-balloon time ⬎120 min. Door-to-balloon time was fractionated into three segments: door-toelectrocardiography time; electrocardiography-to-lab time; and lab-to-balloon time. Each segment of the overall door-to-balloon time was longer in the poorer performing hospitals than in the top performing hospitals. This analysis indicates that the determinants of door-to-balloon time are multifactorial and that institutions need to focus on improving each aspect of the process. Relationship between symptom onset-to-door time and door-to-balloon time. Robert L. McNamara presented an analysis of 29,688 patients from the NRMI registry who received primary PCI for STEMI (15). Patients were stratified by symptom onset-to-door time and those groups were analyzed for outcome according to door-to-balloon time. The principal outcome variable was risk-adjusted death at 30 days. Interestingly, the relationship between door-to-balloon time and death was stronger than the relationship between symptom-to-door time and death. There was a strong relationship between increasing risk of death and increasing door-to-balloon time both in patients with a symptom-to-door time of ⬍2 h and ⬎2 h. Linearizing the mortality rates indicated that each incremental 30-min delay in door-to-balloon time increased mortality risk by 0.3%. Mechanical reperfusion for STEMI after 12 h. It is logical to ask whether there is a point in the evolution of an STEMI beyond which reperfusion no longer provides
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benefit. Albert Schömig presented a randomized trial from nine centers in Germany, Italy, and Austria, in which 365 patients with STEMI, who presented to a PCI center more than 12 h after symptom onset and were not experiencing ongoing ischemia or heart failure, were randomized to emergency PCI or medical therapy (16). End points were infarct size by sestamibi imaging and a composite of death, recurrent MI, and stroke at 30 days. The invasive strategy reduced the scintigraphic estimate of infarct size from 13% to 8% of the LV (p ⫽ 0.0002). There were trends favoring the invasive strategy in both death at 30 days (invasive ⫽ 2%; conservative ⫽ 4%; p ⫽ 0.21) and in the combination of death and recurrent MI (invasive ⫽ 4%; conservative ⫽ 6%; p ⫽ 0.49). These findings indicate that late reperfusion appears to offer incremental benefit over conservative therapy.
CELL THERAPY FOR MI There has been considerable interest in the use of various types of stem cells to repair both acute and old MIs. These trials are still in their infancy and many complex problems exist. Early intracoronary autologous bone marrow stem cells for STEMI. Stefan Janssens presented a randomized trial of autologous bone marrow stem cells versus placebo administered into the infarct artery 24 h after PCI for STEMI (17). End points were global LV contractile function by magnetic resonance imaging, changes in regional contractility by stress echocardiography, and C11 palmitate metabolic imaging, all determined four months after treatment. The results were disappointing in that there was no detectable effect on LV contractile function at four months, although the estimate of metabolic infarct size was slightly reduced in the treatment group at four months. Surgically administered skeletal muscle myoblasts for ischemic cardiomyopathy. Nabil Dib presented the results of surgical direct myocardial injection of skeletal musclederived myoblasts at the time of bypass surgery in 22 patients undergoing surgical revascularization (18). There was no control group. There was evidence of viability in the treated myocardial regions both by positron emission tomographic scanning and by magnetic resonance imaging. Two patients developed non-sustained ventricular tachycardia. These findings appear to indicate that injected autologous myoblasts survive when injected into regions of old MI. Concern remains about the arrhythmic potential of this treatment and the lack of demonstrated efficacy on ventricular function. Percutaneously delivered skeletal muscle myoblasts for old Q-wave MI. Patrick Serruys reported the results of catheter injection of skeletal muscle-derived myoblasts into areas of old Q-wave MI (19). There was no control group. Because of previous experience with ventricular tachycardia, a prophylactic implantable cardioverter-defibrillator was implanted in each patient. Observations were stress echo-
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cardiography at 3, 6, and 12 months after the procedure. Two patients died of arrhythmia during the observation period. There were non-significant trends toward improved LV ejection fraction (baseline ⫽ 34.4%; 12 months ⫽ 36.6%; p ⫽ 0.26), regional resting wall motion score index (baseline ⫽ 3.0; 12 months ⫽ 2.7; p ⫽ 0.049), and dobutamine stress wall motion score index (baseline ⫽ 2.8; 12 months ⫽ 2.5; p ⫽ 0.07).
QUALITY IMPROVEMENT FOR MI MANAGEMENT Guaranteeing quality of care using Guidelines Applied in Practice (GAP). Smit Vasaiwala presented an analysis of the efficacy of reliably applying American College of Cardiology (ACC) guidelines to the management of acute coronary syndromes (20). He studied the outcomes of patients presenting to a single academic health center with acute coronary syndromes. A total of 2,016 were admitted before the institution activated the ACC GAP project that systematizes care of patients with acute coronary syndromes. A total of 618 patients were admitted after the GAP project was started. End points were adherence to guidelines; development of heart failure, stroke, or death while in the hospital; and bleeding while in the hospital. Application of the GAP project led to dramatic improvements both in consistency of care (appropriate use of angiotensinconverting enzyme inhibitors, beta-blockers, and statins) and in outcomes. Heart failure episodes were reduced from 12.9% to 3.6% (p ⬍ 0.001). Stroke was reduced from 1.1% to 0.2% (p ⫽ 0.02). There was a non-significant reduction in death from 4.8% to 4.2% (p ⫽ 0 .53). Major bleeding was reduced dramatically from 7.9% to 1.8% (p ⬍ 0.001). This study confirmed the value of a consistent rigorous approach to care following the ACC guidelines.
MISCELLANEOUS TOPICS Safety of cyclooxygenase (COX)-2 inhibitors in coronary artery bypass grafting (CABG) and other surgery. Andrew Whelton presented an analysis of the use of COX-2 inhibitors as analgesics for postoperative pain after CABG and non-cardiac surgery (21). A total of 1,671 patients undergoing CABG and 1,062 non-cardiac surgical patients were randomized to an intravenous load of parecoxib on postoperative day 1 followed by oral valdecoxib versus placebo. All CABG patients received aspirin. Outcome variables were MI or stroke, gastrointestinal bleeding, and wound complications. The frequency of MI or cerebrovascular accident increased in CABG patients who received the parecoxib/valdecoxib versus placebo (2.0% vs. 0.5%; p ⫽ 0.033). However, there was no difference in event rates in non-cardiac surgery patients (1.0% in both groups). This study suggests that in patients undergoing CABG, COX-2 inhibition increases the risk of thrombotic complications. Pomegranate juice! Michael Sumner presented a randomized trial of 45 patients with stable coronary disease and LV ejection fraction ⬎30% comparing treatment with a daily
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dose of 240 ml of pomegranate juice to placebo (22). Pomegranate juice contains large quantities of polyphenolic antioxidants. The outcome variable was a change in the degree of stress-induced ischemia, using a quantitative scoring system, after three months of treatment. The placebo group’s mean score increased by 1.2, whereas the pomegranate juice group’s mean score decreased by 0.7 (p ⬍ 0.05). This study suggested that long-term treatment with antioxidants is beneficial for reducing the severity of stressprovocable ischemia. Reprint requests and correspondence: Dr. John W. Hirshfeld, Jr., Cardiac Catheterization Laboratory, 9.119 Founders Pavilion, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. E-mail: hirshfel@mail. med.upenn.edu.
REFERENCES 1. Ridker P, Buring S, et al. Low dose aspirin in women in primary prevention: the Women’s Health Study. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 2. Sever P, et al. ASCOT morbidity-mortality outcomes in the blood pressure lowering arm. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 3. LaRosa J, et al. Effect of lowering LDL substantially below current targets: TNT study. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 4. Arant CB, Wessel TR, Ridker PM, et al. Multimarker approach predicts adverse cardiovascular events in women evaluated for suspected ischemia: a report from the NHLBI-sponsored WISE study (abstr). J Am Coll Cardiol 2005;45 Suppl A:223A. 5. Ray KK, Morrow DA, Cannon CP, et al. Inflammation and acute hyperglycemia: a double edged sword in diabetics with non-ST elevation ACS: analyses from the TIMI database (abstr). J Am Coll Cardiol 2005;45 Suppl A:228A. 6. Sabatine M, et al. CLARITY TIMI 28: clopidogrel as an adjunct to thrombolysis. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 7. Chen Z, et al. COMMIT/CCS-2 clopidogrel plus aspirin vs aspirin alone in acute MI. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 8. Goedicke J, Denis M, Arntz HR, et al. Upstream administration of abciximab prior to primary angioplasty improves epicardial patency
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9. 10.
11. 12. 13.
14. 15. 16. 17. 18.
19. 20. 21. 22.
and myocardial tissue perfusion: results from a meta-analysis of 602 cases (abstr). J Am Coll Cardiol 2005;45 Suppl A:250A. Collins R, et al. COMMIT/CCS-2 early metoprolol in acute MI. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Timmer J, et al. GIPS-II Trial Glucose-Insulin-Potassium Study in ST elevation myocardial infarction without congestive heart failure. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Weaver WD, et al. Matrix metalloproteinase inhibitor to prevent remodeling post myocardial infarction. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. O’Neill WW, Grines CL, Sixon SR, et al. Does a 90-minute door to balloon time matter? Observations from four current reperfusion trials (abstr). J Am Coll Cardiol 2005;45 Suppl A:225A. DeLuca G, Suryaparnata H, deBoer, MJ, et al. Inter-hospital delay and mortality in patients with ST-segment elevation myocardial infarction transferred for primary angioplasty (abstr). J Am Coll Cardiol 2005;45 Suppl A:225A. Bradley E, McNamara RL, Herrin J, et al. Door-to-balloon time for acute myocardial infarction: where can we improve (abstr)? J Am Coll Cardiol 2005;45 Suppl A:225A. McNamara RL, Wang Y, Herrin J, et al. Does time from symptom onset to hospital presentation influence importance of time from door-to-balloon (abstr)? J Am Coll Cardiol 2005;45 Suppl A:11A. Schömig A, et al. Multicenter randomized trial of mechanical reperfusion ⬎12 hours postmyocardial infarction. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Janssens S, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Dib N, Kereiakes D, McCarthy P, et al. Three year follow-up of the feasibility and safety of autologous myoblast transplantation for ischemic cardiomyopathy in patients undergoing coronary artery bypass grafting (abstr). J Am Coll Cardiol 2005;45 Suppl A:4A. Serruys P, et al. Late follow-up after percutaneous autologous skeletal myoblast transplantation. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Vasaiwala SC, Nolan E, Fang J, et al. Guaranteeing quality of care in acute coronary syndromes using ACC’s GAP program (abstr). J Am Coll Cardiol 2005;45 Suppl A:17A. Whelton A, et al. Parcoxib and valdecoxib in treatment of post op pain in coronary artery bypass grafting and general surgery. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Sumner MD, Elliot-Eller M, Weidner G, et al. Effect of pomegranate juice on myocardial perfusion in patients with coronary heart disease: a randomized, placebo-controlled double-blind study (abstr). J Am Coll Cardiol 2005;45 Suppl A:17A.
Vol. 45, No. 11 Suppl B ISSN 0735-1097/05/$30.00 doi:10.1016/j.jacc.2005.05.011
Myocardial Ischemia and Infarction John W. Hirshfeld, JR, MD, FACC Philadelphia, Pennsylvania A total of 828 abstracts were submitted in the various myocardial ischemia and infarction categories. Of these, 297 were accepted for presentation. The presented abstracts may be grouped into seven topical categories. 1. Prevention of coronary heart disease (CHD) 2. Risk prediction for CHD 3. Pharmacologic treatment for ST-segment elevation myocardial infarction (STEMI) 4. Reperfusion treatment for STEMI 5. Advances in cell therapy for CHD 6. Quality management and improvement in myocardial infarction (MI) 7. Miscellaneous topics This article summarizes the most significant presentations.
PREVENTION OF CHD Role of aspirin and vitamin E in preventing coronary events in women. Paul Ridker and Stacy Buring presented the results of the Women’s Health Study Research Group randomized trial of primary prevention of CHD in 39,876 initially healthy female health professionals age ⬎45 years (1). Subjects were randomized in a double factorial randomization scheme to 100 mg of aspirin every other day versus placebo and 600 mg vitamin E every other day versus placebo. Follow-up was 10.1 years. The end points were cardiovascular mortality, nonfatal MI, and nonfatal stroke. The aspirin arm of the trial was positive and the vitamin E arm was negative. Because this was a very healthy population, the overall end point event rate was small at 2.5% over a 10-year observation period. Aspirin reduced the end point event rate by 9%, which was not statistically significant (p ⫽ 0.13). The reduction was leveraged by a significant reduction in the rate of ischemic stroke (relative risk ⫽ 0.76; p ⫽ 0.009). There was no effect on all-cause mortality or cardiovascular death. This study demonstrates a modest protective effect of aspirin, even in a low-risk population, and confirms the lack of effectiveness of vitamin E. Blood pressure (BP)-lowering strategy revisited. Peter Sever presented the findings of the (Anglo-Scandanavian Cardiac Outcomes Trial (ASCOT) blood pressurelowering arm (2). This trial compared two different pharmacologic strategies for lowering BP (amlodipine ⫾ perindopril vs. atenolol ⫾ benzoflumethazide) in 19,257 hypertensive men and women. The protocol treated patients to a BP ⬍140/90 mm Hg for non-diabetics and 130/80 mm Hg for diabetics. Amlodipine or atenolol were started From the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
initially and perindopril or benzoflumethazide were added if target BP was not achieved with a single drug. Follow-up was 5.1 years. End points were cardiovascular mortality and nonfatal MI. The majority of patients required both drugs to achieve target BP. The trial was stopped prematurely by the safety committee because of the emergence of superiority in the amlodipine/perindopril group. The primary end point was reduced by 10% from 4.6% to 4.1%. Other multiple cardiovascular end points were reduced in the amlodipine/perindopril group (stroke 30%, all coronary events 13%, all cardiovascular events and procedures 16%, cardiovascular mortality 16%). The trial demonstrates the superiority of the amlodipine/perindopril strategy. The difference between the strategies was not due to differences in BP because both groups achieved the same target BP levels. Thus, the difference must be due to the different drug classes used. Because the majority of patients received both drugs, one cannot determine whether one of the drugs in the trial arm pair was predominantly responsible for the difference. Aggressive low-density lipoprotein (LDL) lowering. John LaRosa presented the results of the Treating to New Targets (TNT) trial. Patients with clinically evident coronary disease were enrolled (n ⫽ 10,002) (3). Eligibility required that subjects achieve an LDL below 130 mg/dl on 10 mg of atorvastatin. Eligible subjects were then randomized between continuing 10 mg of atorvastatin and advancing to 80 mg of atorvastatin. Patients were followed until the design-required number of end point events (cardiovascular mortality, nonfatal MI, resuscitated cardiac arrest, or stroke) had been accumulated (five years). The 10 mg atorvastatin group achieved a mean LDL of 100 mg/dl, whereas the mean LDL for the 80 mg atorvastatin group was 80 mg/dl. The frequency of end point events was reduced in the 80 mg atorvastatin group (10.0% vs. 12.2%; p ⫽ 0.002). There was no difference between the two groups in the frequency of statin-related side effects. This study validates the concept that, with LDL cholesterol, lower is better.
CHD RISK PREDICTION Two studies were presented that endeavored to refine the ability to predict future coronary risk. Multimarker approach to risk prediction. Christopher Arant, representing the Women’s Ischemia Syndrome Evaluation (WISE) team, investigated a high-risk population of 595 women who were being evaluated for suspected myocardial ischemia (4). The population had a high prevalence of traditional coronary risk factors. They were further risk
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stratified by markers of inflammation— high-sensitivity C-reactive protein (hs-CRP), interleukin-6, and serum amyloid antigen. The women were followed for a mean of 3.6 years with end points of all-cause death, hospitalization for MI, congestive heart failure, stroke, or other vascular events. The annual risk of an end point event increased progressively if two or more abnormal markers were present (0 or 1 marker ⫽ 1.90%; 2 ⫽ 3.68%; 3 ⫽ 5.5%). These findings are consistent with the importance of inflammatory markers as predictors of vascular risk independently of other risk factors. Inflammation and hyperglycemia. Kausik K. Ray, representing the Thrombolysis In Myocardial Infarction (TIMI) investigators, conducted a pooled analysis of the patients enrolled in four TIMI trials (5). Patients with acute coronary syndromes were categorized by the presence or absence of diabetes, and within diabetics, by tertiles of glucose level. Patients were also characterized by levels of hs-CRP. Diabetic patients, as a group, had higher levels of hs-CRP than non-diabetics. End points were death or MI over 10 months. Both diabetes and hs-CRP were predictive of events, with diabetes being the stronger predictor. Nondiabetics with low hs-CRP levels had an 18% event rate compared with 33% for diabetics with elevated hs-CRP levels. The worst outcomes were in diabetics with elevated hs-CRP levels whose random glucose was in the top tertile. This study demonstrates, once again, that diabetes is a powerful adverse risk factor and the hs-CRP level adds independent incremental risk prediction.
PHARMACOLOGIC TREATMENT OF STEMI Studies of both classical as well as novel therapeutic approaches to the treatment of STEMI were presented. The classical approaches involved refinements of antiplatelet and beta-blocker therapy. The novel approaches examined an old and a new treatment strategy. Clopidogrel was studied in two randomized STEMI trials, both of which demonstrated benefit for adjunctive concomitant clopidogrel therapy at the time of presentation with STEMI. Clopidogrel as an adjunct to thrombolysis. Marc Sabatine, representing the TIMI-28 study group, presented the results of the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) trial (6). This trial randomized 3,496 patients who had undergone intravenous fibrinolysis for STEMI to an antiplatelet regimen of aspirin alone compared with aspirin plus a 300-mg load of clopidogrel followed by a daily dose of 75 mg. Patients subsequently underwent angiography at a median of 3.5 days after fibrinolysis. Efficacy end points included death, recurrent MI, or an occluded infarct artery. The safety end point was TIMI major bleeding. The primary end point through the time of angiography was reduced from 21.7% to 15.0% (odds ratio 0.64; p ⬍ 0.001) and was leveraged predomi-
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nantly by greater infarct artery patency at the time of elective angiography. The frequency of TIMI major bleeding was similar in both treatment groups, although TIMI minor bleeding was slightly, but not statistically, significantly increased (1.0% vs. 0.5%; p ⫽ 0.17) in the clopidogrel group. This study demonstrated a benefit of clopidogrel therapy in patients who do not receive prompt invasive evaluation and treatment. Clopidogrel as an adjunct to aspirin. Clopidogrel was also studied as an adjunct to standard therapy with aspirin in patients with STEMI who mostly did not receive subsequent invasive therapy (7). Zhenming Chen reported the results of the Clopidogrel and Metoprolol in Myocardial Infarction (COMMIT/CCS2) study, which enrolled 46,000 patients presenting with STEMI at 1,250 hospitals in China. The patients were randomized to receive aspirin alone or aspirin plus 75 mg of clopidogrel per day (no loading dose) for 30 days. Fifty-two percent of the patients received thrombolytic therapy. The end point was a composite of death, nonfatal re-infarction, and stroke. The clopidogrel group had a 9% reduction in the end point (9.3% vs. 10.1%; p ⫽ 0.002) at 30 days. The primary end point difference was driven mainly by a reduction in mortality (7.3% vs. 8.1%; p ⫽ 0.03). Upstream administration of abciximab. Jochen Goedicke presented a meta-analysis of six clinical trials of primary percutaneous coronary intervention (PCI) for STEMI comparing the outcomes of patients who received abciximab before angiography (upstream) compared with receiving it at the time of PCI (8). The primary end point was a composite of death, re-infarction, and target vessel revascularization at 30 days. Upstream abciximab patients received the drug an average of 50 min before PCI compared with 5 min in the non-upstream group. Infarct artery patency at the time of angiography was greater in the upstream group (43% vs. 29%; p ⫽ 0.001). This resulted in a nonstatistically significant decrease in the frequency of the composite end point (7.3% vs. 9.7%) and a non-statistically significant decrease in the frequency of death (2.7% vs. 4.7%). There was no difference in the frequency of major bleeding (3.5% vs. 3.8%). This study indicates that upstream administration of abciximab appears to improve outcomes in primary PCI for STEMI. Early administration of metoprolol. The COMMIT/ CCS2 trial was a two-armed multifactorial design trial. The second arm was a randomization to metoprolol versus placebo (9). Patients with STEMI who were randomized to metoprolol therapy received three 5-mg intravenous boluses of metoprolol followed by a daily oral dose of 200 mg for 30 days. The end point events were the same as in the clopidogrel arm of the trial. The results of this trial were more complex to interpret. Overall, there was no effect on mortality (metoprolol 7.7% vs. placebo 7.8%). However, metoprolol reduced the frequency of ventricular fibrillation (2.5% vs. 3.9%). There was an increased mortality in patients who presented with hemodynamic instability that
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offset a trend toward improved mortality in nonhemodynamically compromised patients. The conclusion from the trial was that metoprolol appeared to be beneficial in patients without hemodynamic compromise, but that it was likely detrimental to compromised patients. Glucose-insulin-potassium (GIK) revisited. There has been a 30-year controversy over whether administration of a GIK solution is beneficial in the early phases of STEMI. The Glucose Insulin Potassium Study (GIPS I) had suggested a possible benefit of high-dose GIK in Killip class I patients. Jorik Timmer presented the results of the GIPS II trial, which was confined to high-dose GIK in Killip class I STEMI patients (10). End points were death at 30 days, enzymatic infarct size, and left ventricular (LV) function. The trial was stopped early by the Data Safety and Monitoring Committee because of lack of effect on enzymatic infarct size and a non-significant trend toward increased mortality (2.9% vs. 1.8%; p ⫽ 0.26) in the GIK treatment group. Thus, the findings of the GIPS I trial were not confirmed and there seems to be little rationale for GIK therapy for STEMI. Matrix metalloproteinase (MMP) inhibition. W. Douglas Weaver presented a randomized trial assessing the efficacy of acute treatment with PG116800, a MMP inhibitor, with the goal to prevent ventricular remodeling after STEMI (11). The trial enrolled 253 patients undergoing primary PCI for STEMI. The population had major MIs (80% anterior, LV ejection fraction 15% to 40%). End points were a change in LV ejection fraction, a change in serum pro-brain natriuretic peptide, a change in hs-CRP, and a composite clinical end point of new or worsening congestive heart failure, hospitalization for congestive heart failure, or death. Analysis of the data revealed no detectable effect of the treatment, indicating that MMP inhibition does not appear to affect remodeling or outcome after STEMI.
REPERFUSION TREATMENT OF STEMI Many studies assessing refinement of reperfusion treatment for STEMI were presented. The predominant theme was to re-evaluate the 90-min door-to-balloon time standard. Does a 90-min door-to-balloon time matter? William W. O’Neill presented the results of a pooled analysis of four trials of PCI for STEMI (Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Debris [EMERALD], COOL MI feasibility trial [COOL], Acute Myocardial Infarction HyperOxemia Trial [AMI-HOT], Intravascular Cooling Adjunctive to Primary Coronary Intervention [ICE-IT]) (12). A total of 1,355 patients were available for analysis and were stratified by symptom onsetto-door time and door-to-balloon time. Outcome variables were death at 30 days, major cardiac adverse events at 30 days, and infarct size by sestamibi imaging. Both symptom onset-to-balloon time (p ⫽ 0.025) and door-to-balloon time (p ⬍ 0.0001) were independently associated with death
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at 30 days. Each outcome variable showed a graded relationship with door-to-balloon time up to 90 min, after which the relationship appeared to flatten. Interhospital transfer delay and mortality of STEMI. Giuseppe DeLuca examined outcomes in 616 patients who were transferred to a single hospital for primary PCI for STEMI (13). The institution’s mean door-to-balloon time was 38 min. Patients were stratified by the time delay between arrival at the first hospital and arrival at the referral hospital. End points were death at one year, myocardial blush grade, and serum lactate dehydrogenase (LDH) at 48 h after the PCI. Statistically significant associations were found for LDH at 24 h (p ⫽ 0.049) and death at 1 year (p ⫽ 0.01). There was a strong trend toward improving myocardial blush grade with shorter delay times. The association with death was particularly strong (⬍30 min ⫽ 3.2%; 30 to 59 min ⫽ 6.4%; 60 to 89 min ⫽ 6.2%; ⱖ90 min ⫽ 12.1%). Both the previously cited studies strongly reaffirm the importance of minimizing time to reperfusion in the management of STEMI. Two other studies examined the National Registry of Myocardial Infarction (NRMI) to focus on strategies to shorten door-to-balloon time. Door-to-balloon time: where can we improve? Elizabeth Bradley presented an analysis of 13,387 patients from the NRMI registry who received PCI for STEMI at 340 participating hospitals (14). Hospitals were separated into two groups: median door-to-balloon time ⬍90 min and median door-to-balloon time ⬎120 min. Door-to-balloon time was fractionated into three segments: door-toelectrocardiography time; electrocardiography-to-lab time; and lab-to-balloon time. Each segment of the overall door-to-balloon time was longer in the poorer performing hospitals than in the top performing hospitals. This analysis indicates that the determinants of door-to-balloon time are multifactorial and that institutions need to focus on improving each aspect of the process. Relationship between symptom onset-to-door time and door-to-balloon time. Robert L. McNamara presented an analysis of 29,688 patients from the NRMI registry who received primary PCI for STEMI (15). Patients were stratified by symptom onset-to-door time and those groups were analyzed for outcome according to door-to-balloon time. The principal outcome variable was risk-adjusted death at 30 days. Interestingly, the relationship between door-to-balloon time and death was stronger than the relationship between symptom-to-door time and death. There was a strong relationship between increasing risk of death and increasing door-to-balloon time both in patients with a symptom-to-door time of ⬍2 h and ⬎2 h. Linearizing the mortality rates indicated that each incremental 30-min delay in door-to-balloon time increased mortality risk by 0.3%. Mechanical reperfusion for STEMI after 12 h. It is logical to ask whether there is a point in the evolution of an STEMI beyond which reperfusion no longer provides
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benefit. Albert Schömig presented a randomized trial from nine centers in Germany, Italy, and Austria, in which 365 patients with STEMI, who presented to a PCI center more than 12 h after symptom onset and were not experiencing ongoing ischemia or heart failure, were randomized to emergency PCI or medical therapy (16). End points were infarct size by sestamibi imaging and a composite of death, recurrent MI, and stroke at 30 days. The invasive strategy reduced the scintigraphic estimate of infarct size from 13% to 8% of the LV (p ⫽ 0.0002). There were trends favoring the invasive strategy in both death at 30 days (invasive ⫽ 2%; conservative ⫽ 4%; p ⫽ 0.21) and in the combination of death and recurrent MI (invasive ⫽ 4%; conservative ⫽ 6%; p ⫽ 0.49). These findings indicate that late reperfusion appears to offer incremental benefit over conservative therapy.
CELL THERAPY FOR MI There has been considerable interest in the use of various types of stem cells to repair both acute and old MIs. These trials are still in their infancy and many complex problems exist. Early intracoronary autologous bone marrow stem cells for STEMI. Stefan Janssens presented a randomized trial of autologous bone marrow stem cells versus placebo administered into the infarct artery 24 h after PCI for STEMI (17). End points were global LV contractile function by magnetic resonance imaging, changes in regional contractility by stress echocardiography, and C11 palmitate metabolic imaging, all determined four months after treatment. The results were disappointing in that there was no detectable effect on LV contractile function at four months, although the estimate of metabolic infarct size was slightly reduced in the treatment group at four months. Surgically administered skeletal muscle myoblasts for ischemic cardiomyopathy. Nabil Dib presented the results of surgical direct myocardial injection of skeletal musclederived myoblasts at the time of bypass surgery in 22 patients undergoing surgical revascularization (18). There was no control group. There was evidence of viability in the treated myocardial regions both by positron emission tomographic scanning and by magnetic resonance imaging. Two patients developed non-sustained ventricular tachycardia. These findings appear to indicate that injected autologous myoblasts survive when injected into regions of old MI. Concern remains about the arrhythmic potential of this treatment and the lack of demonstrated efficacy on ventricular function. Percutaneously delivered skeletal muscle myoblasts for old Q-wave MI. Patrick Serruys reported the results of catheter injection of skeletal muscle-derived myoblasts into areas of old Q-wave MI (19). There was no control group. Because of previous experience with ventricular tachycardia, a prophylactic implantable cardioverter-defibrillator was implanted in each patient. Observations were stress echo-
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cardiography at 3, 6, and 12 months after the procedure. Two patients died of arrhythmia during the observation period. There were non-significant trends toward improved LV ejection fraction (baseline ⫽ 34.4%; 12 months ⫽ 36.6%; p ⫽ 0.26), regional resting wall motion score index (baseline ⫽ 3.0; 12 months ⫽ 2.7; p ⫽ 0.049), and dobutamine stress wall motion score index (baseline ⫽ 2.8; 12 months ⫽ 2.5; p ⫽ 0.07).
QUALITY IMPROVEMENT FOR MI MANAGEMENT Guaranteeing quality of care using Guidelines Applied in Practice (GAP). Smit Vasaiwala presented an analysis of the efficacy of reliably applying American College of Cardiology (ACC) guidelines to the management of acute coronary syndromes (20). He studied the outcomes of patients presenting to a single academic health center with acute coronary syndromes. A total of 2,016 were admitted before the institution activated the ACC GAP project that systematizes care of patients with acute coronary syndromes. A total of 618 patients were admitted after the GAP project was started. End points were adherence to guidelines; development of heart failure, stroke, or death while in the hospital; and bleeding while in the hospital. Application of the GAP project led to dramatic improvements both in consistency of care (appropriate use of angiotensinconverting enzyme inhibitors, beta-blockers, and statins) and in outcomes. Heart failure episodes were reduced from 12.9% to 3.6% (p ⬍ 0.001). Stroke was reduced from 1.1% to 0.2% (p ⫽ 0.02). There was a non-significant reduction in death from 4.8% to 4.2% (p ⫽ 0 .53). Major bleeding was reduced dramatically from 7.9% to 1.8% (p ⬍ 0.001). This study confirmed the value of a consistent rigorous approach to care following the ACC guidelines.
MISCELLANEOUS TOPICS Safety of cyclooxygenase (COX)-2 inhibitors in coronary artery bypass grafting (CABG) and other surgery. Andrew Whelton presented an analysis of the use of COX-2 inhibitors as analgesics for postoperative pain after CABG and non-cardiac surgery (21). A total of 1,671 patients undergoing CABG and 1,062 non-cardiac surgical patients were randomized to an intravenous load of parecoxib on postoperative day 1 followed by oral valdecoxib versus placebo. All CABG patients received aspirin. Outcome variables were MI or stroke, gastrointestinal bleeding, and wound complications. The frequency of MI or cerebrovascular accident increased in CABG patients who received the parecoxib/valdecoxib versus placebo (2.0% vs. 0.5%; p ⫽ 0.033). However, there was no difference in event rates in non-cardiac surgery patients (1.0% in both groups). This study suggests that in patients undergoing CABG, COX-2 inhibition increases the risk of thrombotic complications. Pomegranate juice! Michael Sumner presented a randomized trial of 45 patients with stable coronary disease and LV ejection fraction ⬎30% comparing treatment with a daily
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dose of 240 ml of pomegranate juice to placebo (22). Pomegranate juice contains large quantities of polyphenolic antioxidants. The outcome variable was a change in the degree of stress-induced ischemia, using a quantitative scoring system, after three months of treatment. The placebo group’s mean score increased by 1.2, whereas the pomegranate juice group’s mean score decreased by 0.7 (p ⬍ 0.05). This study suggested that long-term treatment with antioxidants is beneficial for reducing the severity of stressprovocable ischemia. Reprint requests and correspondence: Dr. John W. Hirshfeld, Jr., Cardiac Catheterization Laboratory, 9.119 Founders Pavilion, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104. E-mail: hirshfel@mail. med.upenn.edu.
REFERENCES 1. Ridker P, Buring S, et al. Low dose aspirin in women in primary prevention: the Women’s Health Study. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 2. Sever P, et al. ASCOT morbidity-mortality outcomes in the blood pressure lowering arm. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 3. LaRosa J, et al. Effect of lowering LDL substantially below current targets: TNT study. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 4. Arant CB, Wessel TR, Ridker PM, et al. Multimarker approach predicts adverse cardiovascular events in women evaluated for suspected ischemia: a report from the NHLBI-sponsored WISE study (abstr). J Am Coll Cardiol 2005;45 Suppl A:223A. 5. Ray KK, Morrow DA, Cannon CP, et al. Inflammation and acute hyperglycemia: a double edged sword in diabetics with non-ST elevation ACS: analyses from the TIMI database (abstr). J Am Coll Cardiol 2005;45 Suppl A:228A. 6. Sabatine M, et al. CLARITY TIMI 28: clopidogrel as an adjunct to thrombolysis. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 7. Chen Z, et al. COMMIT/CCS-2 clopidogrel plus aspirin vs aspirin alone in acute MI. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. 8. Goedicke J, Denis M, Arntz HR, et al. Upstream administration of abciximab prior to primary angioplasty improves epicardial patency
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and myocardial tissue perfusion: results from a meta-analysis of 602 cases (abstr). J Am Coll Cardiol 2005;45 Suppl A:250A. Collins R, et al. COMMIT/CCS-2 early metoprolol in acute MI. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Timmer J, et al. GIPS-II Trial Glucose-Insulin-Potassium Study in ST elevation myocardial infarction without congestive heart failure. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Weaver WD, et al. Matrix metalloproteinase inhibitor to prevent remodeling post myocardial infarction. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. O’Neill WW, Grines CL, Sixon SR, et al. Does a 90-minute door to balloon time matter? Observations from four current reperfusion trials (abstr). J Am Coll Cardiol 2005;45 Suppl A:225A. DeLuca G, Suryaparnata H, deBoer, MJ, et al. Inter-hospital delay and mortality in patients with ST-segment elevation myocardial infarction transferred for primary angioplasty (abstr). J Am Coll Cardiol 2005;45 Suppl A:225A. Bradley E, McNamara RL, Herrin J, et al. Door-to-balloon time for acute myocardial infarction: where can we improve (abstr)? J Am Coll Cardiol 2005;45 Suppl A:225A. McNamara RL, Wang Y, Herrin J, et al. Does time from symptom onset to hospital presentation influence importance of time from door-to-balloon (abstr)? J Am Coll Cardiol 2005;45 Suppl A:11A. Schömig A, et al. Multicenter randomized trial of mechanical reperfusion ⬎12 hours postmyocardial infarction. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Janssens S, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Dib N, Kereiakes D, McCarthy P, et al. Three year follow-up of the feasibility and safety of autologous myoblast transplantation for ischemic cardiomyopathy in patients undergoing coronary artery bypass grafting (abstr). J Am Coll Cardiol 2005;45 Suppl A:4A. Serruys P, et al. Late follow-up after percutaneous autologous skeletal myoblast transplantation. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Vasaiwala SC, Nolan E, Fang J, et al. Guaranteeing quality of care in acute coronary syndromes using ACC’s GAP program (abstr). J Am Coll Cardiol 2005;45 Suppl A:17A. Whelton A, et al. Parcoxib and valdecoxib in treatment of post op pain in coronary artery bypass grafting and general surgery. Presented at: ACC 54th Annual Scientific Session; March 6 –9, 2005; Orlando, FL. Sumner MD, Elliot-Eller M, Weidner G, et al. Effect of pomegranate juice on myocardial perfusion in patients with coronary heart disease: a randomized, placebo-controlled double-blind study (abstr). J Am Coll Cardiol 2005;45 Suppl A:17A.