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[Coronary revascularization: off-pump versus on-pump--a comparison of behavior of biochemical cardiac ischemia markers].

BACKGROUND: Recently, coronary artery bypass grafting (CABG) on the beating heart with avoidance of extracorporeal circulation (off-pump CABG technique) has been gaining increasing importance in modern cardiac surgery. The object of this prospective study was to compare postoperative kinetic and patterns of cardiac troponin I (cTnI), T (cTnT), and creatine kinase MB (CKMB) activities after off-pump CABG versus conventional on-pump CABG. METHODS: We studied 106 patients who underwent first-time elective on-pump (group I, n = 69, 56 male, 13 female, mean age: 64.3 +/- 9.9 years, mean ejection fraction: 56 +/- 15%) or off-pump (group II, n = 37, 24 male, 13 female, mean age: 68.4 +/- 9.1 years, mean ejection fraction: 57 +/- 13%) CABG surgery via median sternotomy. CTn I and cTnT levels, total creatine kinase (CK) and CK-MB activities in the serum were measured before operation, up on arrival at the ICU and 6, 12, 24, 48 and 120 hours later. Serial 12-lead ECGs were recorded preoperatively and on days 1, 2 and 5. RESULTS: Serum concentrations of cardiac troponins in all patients were preoperatively either not detectable or in the normal range and significantly increased after surgery. In group I, one patient developed a Q wave myocardial infarction, one patient a non-Q wave infarction and two patients a new left bundle branch block on the ECG. One patient of group II developed a new Q-wave myocardial infarction and another patient permanent atrial fibrillation associated with a continuous arrhythmia. All patients with a myocardial infarction in the ECG showed significant elevation of concentrations or activities of these biochemical markers. The median postoperative peak values for cTnI were measured at 24 h in both groups (2.7 micrograms/l, 95%-CI: [2.2, 3.2] in group I and 1.1 micrograms/l, 95%-CI: [0.5, 1.3] in group II). CTnT postoperatively presented an earlier median peak of 0.128 microgram/l at 12 h in group II (95%-CI: [0.041, 0.146]) than in group I at 48 h (0.298 microgram/l, 95%-CI: [0.254, 0.335]). CONCLUSIONS: All patients undergoing CABG surgery with or without extracorporeal circulation postoperatively showed an increase of cardiac troponin levels. After uncomplicated coronary revascularization, patients with the off-pump CABG technique continuously presented lower serum cardiac troponin concentrations than those with the on-pump CABG technique. CTnI showed the same patterns of release in both groups with different median postoperative peak values at 24 h. The patterns off cTnT release following CABC surgery with or without extracorporal circulation were different: CTnT reaches its postoperative peak value in patients with the off-pump CABG technique earlier than those with the on-pump CABG technique (12 h postoperatively versus 48 h).

Aged↗

Level of circulating phospholipase A2 in prediction of the prognosis of patients with suspected myocardial infarction.

OBJECTIVES: Atherosclerotic lesions result from inflammatory-proliferative responses of the endothelium and smooth muscle of the arterial wall. Poor prognosis of acute myocardial infarction (AMI) patients has been associated with elevated levels of acute phase proteins including C-reactive protein. We investigated the significance of circulating phospholipase A2 in the long-term prognosis of suspected AMI patients. METHODS: The concentration of phospholipase A2 was measured by an immunoassay in sera of 100 suspected AMI patients. Admission phospholipase A2 95 % fractile outliers were excluded to eliminate the effect of acute infectious diseases. The total and atherosclerotic mortalities were followed for a 4-year period. RESULTS: The most powerful prognostic limit for both admission (p = 0.02, RR = 2.6 and 95% CI = 1.2 to 5.6) and maximal (p = 0.06, RR = 2.4 and 95% CI = 0.96 to 5.9) phospholipase A2 groups was > or =8 microg/l. The admission phospholipase A2 level had an independent prognostic significance for atherosclerotic mortality (p = 0.04, RR = 2.4 and CI = 1.02 to 5.8) in multivariate analysis with CK-MB and age. CONCLUSIONS: The elevated serum phospholipase A2 level at admission is an independent predictor of long-term atherosclerotic mortality in patients with suspected AMI. The prognostic significance of phospholipase A2 weakens during hospitalisation concomitant to the onset of the acute inflammatory response to myocardial injury.

Aged↗

Cardiac ischemia during hemolytic uremic syndrome.

Increased thrombin generation and impaired fibrinolysis during Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) plausibly diminish myocardial blood flow, but the frequency of cardiac ischemia during HUS is unknown. We identified a 9-year-old boy with HUS in whom myocardial diastolic dysfunction was demonstrated by echocardiography, who also had elevated serum troponin-I and creatine kinase MB mass. However, eight additional patients with HUS did not have elevated markers of cardiac injury. When present, elevated troponin-I should be considered to represent myocardial injury, and not attributed simply to renal insufficiency. It is possible that myocardial ischemia and secondary arrhythmias account for some sudden deaths that occur during acute HUS.

Biomarkers↗

Newly developed T-wave inversion with cardiac wall-motion abnormality predominantly occurs in middle-aged or elderly women after noncardiac surgery.

PURPOSE: The study was done to determine the characteristics and prevalence of myocardial ischemia with inverted T waves after noncardiac surgery. METHODS: A list of patients who developed electrocardiogram (ECG) T-wave inversion associated with wall-motion abnormalities observed by transthoracic echocardiography (TTE) following noncardiac surgery was generated from the intensive care unit (ICU) medical records database between January 1, 1995, and December 31, 2000. The hospital records of these patients were analyzed retrospectively. RESULTS: Among 4219 patients (2187 men and 2032 women) who were admitted to the ICU after noncardiac surgery, 13 developed myocardial ischemia with inverted T waves postoperatively. All of the patients were middle-aged or elderly women with no history of coronary artery disease; nine of them had undergone intraabdominal surgery. Characteristic ECG findings included inverted T waves in the left precordial leads, which subsequently became prominent with QT prolongation. In all of these patients, wall-motion abnormalities were observed on the anterior wall, but these resolved within 60 days of the episode. Myocardial ischemia was asymptomatic, with neither hemodynamic changes nor adverse cardiac events. CONCLUSION: Newly developed giant negative T waves with QT prolongation in the ECG may indicate myocardial stunning, but do not in themselves imply a poor prognosis. The marked preponderance of middle-aged and elderly women with this type of myocardial ischemia remains to be explained.

Aged↗

Serum levels of cardiac troponin I and other marker proteins in patients with chronic renal failure.

BACKGROUND: Serum levels ob biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF. METHODS: Subjects consisted of 59 healthy volunteers and 102 patients: 61 with CRF undergoing hemodialysis (CRF-HD), 10 with CRF under conservative therapy (CRF-CT), 21 with renal disease (RD), and 10 with muscle disease (MD). Patients with RD, CRF, and MD were evaluated to verify the absence of myocardial injury. We developed an immunoradiometric assay to measure serum cTnI using monoclonal antibodies. The lower limit of detection was 0.33 micro g/l. Serum cTnI, creatine kinase (CK), CK-MB, cardiac troponin T (first-, second-, and third-generation assay: cTnT-I, cTnT-II, and cTnT-III), and cardiac myosin light chain 1 (cMLC1) were measured. RESULTS: cTnI was not detected in healthy volunteers or patients with CRF, RD, or MD. In patients with CRF-HD, elevated levels occurred in 4.9% (3/61) for CK, 0% (0/61) for CK-MB, 39.5% (15/38) for cTnT-I, 7.3% (3/41) for cTnT-II, 13.0% (3/23) for cTnT-III, and 77.0% (47/61) for cMLC1; and in patients with MD the levels were increased in 70% (7/10) for CK, 50% (5/10) for CK-MB, 44.4% (4/9) for cTnT-I, 20% (2/10) for cTnT-II, and 50% (5/10) for cMLC1. CONCLUSIONS: cTnI is a highly specific marker for AMI and is particularly useful for detecting AMI in patients with CRF or MD. Serum levels of biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF.

Biomarkers↗

A case of hypothyroidism mimicking acute coronary syndrome.

Hypothyroid patients have increased concentrations of creatinine kinase that is mostly due to increased CK-MM. However, CK-MB has also been reported to increase above reference values in hypothyroid patients without apparent myocardial damage. This may create confusion during the evaluation of myocardial injury in a hypothyroid patient presenting with chest pain. Troponin I is considered as a superior marker for the diagnosis of myocardial infarction in hypothyroid patients. However, there are some reports showing an increase in the level of troponin I without any myocardial damage in hypothyroid patients as in our case. In this report, we present a 47 years old male hypothyroid patient who had chest pain, abnormal electrocardiographic findings and increased cardiac enzymes suggesting acute coronary syndrome although he had normal coronary arteriogram.

Acute Disease↗

Diagnostic accuracy of cardiac markers for myocardial damage after radiofrequency catheter ablation.

AIMS: This study compares serum markers of myocardial damage incurred during radiofrequency catheter ablation (RFCA). METHODS AND RESULTS: Blood was sampled from 34 patients with atrial flutter (n = 16), atrioventricular nodal reentrant tachycardia (AVNRT; n = 13), and Wolff-Parkinson-White syndrome (WPW; n = 5) to measure creatine kinase MB subfraction (CK-MB), human heart-type fatty acid protein (h-FABP), and cardiac troponin T (cTnT) values at baseline and after RFCA. The controls comprised 12 patients without significant elevation of all myocardial markers during electrophysiological study (EPS) without RFCA. h-FABP values did not elevate significantly, whereas CK-MB and cTnT demonstrated significant change after RFCA (P < 0.001). Neither peak h-FABP nor CK-MB correlated with following RFCA parameters: delivery duration, number of RFCA discharges, and cumulative RFCA energy. In contrast, correlations were significant between mean peak values of cTnT and these RFCA parameters (all P < 0.05). The sensitivity (71.6%) and specificity (35.6%) of h-FABP were inferior to those of cTnT (93.3% and 89.8%, respectively). CONCLUSION: h-FABP is an insensitive and less specific marker of myocardial damage in RFCA much along the lines of CK-MB and when compared with the proven accuracy of cTnT.

Adult↗

Prevention of doxorubicin-induced cardiotoxicity by melatonin.

Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents. Cardiotoxicity made by these agents develops as a complication of the cancer chemotherapy. Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. We decided to evaluate the tissue-protective effect of melatonin against myocardial toxic effects of doxorubicin in six groups of rats. Rats were given doxorubicin (Dx) (45 mg/kg dose) and melatonin (MEL) (10 mg/kg), first doxorubicin and then melatonin (DM), first melatonin and then doxorubicin (MD). The degree of cardiac muscle cell alterations were examined either histologically (mean total score technique) or biochemically. In doxorubicin-treated group, malondialdehyde (MDA) levels of the heart tissue were significantly increased, glutathione (GSH) levels were decreased compared to the control rats. In the group in which first doxorubicin and then melatonin was given, MDA levels were significantly decreased and glutathione (GSH) levels were increased compared to the doxorubicin-treated group. During ultrastructural analysis, in doxorubicin-treated group, cellular edema, mitochondrial deformation, decreased glycogen stores, and disordered myofibrillary structure were observed. In contrast, in first doxorubicin and then melatonin-treated group, normal cellular structure was observed. But, first melatonin and then doxorubicin-treated group was not significantly preserved from the doxorubicin-induced changes. By preventing lipid peroxidation and myocardial lesions, melatonin may be highly effective in protecting against doxorubicin-induced cardiotoxicity.

Animals↗

Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury.

The efficacy of lycopene to limit myocardial injury after ischemia and reperfusion was explored in the present study. Adult male albino Wistar rats were divided into three experimental groups and orally received olive oil as vehicle (sham and control I-R) or lycopene 1 mg/kg dissolved in olive oil (lycopene treated group) respectively for 31 days. On the 31st day, animals of the control I-R and lycopene treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. The ischemia-reperfusion injury resulted in significant cardiac necrosis, depression in hemodynamics, decline in antioxidant status and rise in lipid peroxidation product levels in the control I-R group as compared to sham control. In histopathological examinations myocardial damage produced after I-R was significantly prevented in the lycopene treated group. Lycopene treatment resulted in preservation of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I-R group. Furthermore, I-R-induced lipid peroxidation was significantly inhibited in the lycopene treated group. These beneficial cardioprotective effects also translated into the functional recovery of the heart. The beneficial effect of lycopene likely results from the suppression of oxidative stress, which results in the reduction of myocardial injury.

Animals↗

Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records.

BACKGROUND: Many cardiovascular epidemiologic studies rely on diagnosis codes in health care claims databases. Despite important changes in the care and diagnosis of acute myocardial infarction (AMI), the validity of hospital discharge diagnosis codes for AMI in the US Medicare system has not been recently examined. Our objective was to examine the accuracy of International Classification of Diseases--ninth revision--Clinical Modifications (ICD-9-CM) discharge diagnosis codes and diagnosis-related groups (DRG) codes for AMI in a Medicare claims database. METHODS: We sampled hospitalization episodes from Medicare beneficiaries in Pennsylvania during 1999, 2000, or both. We used Medicare data to identify patients with hospitalizations containing indicators of AMI (ICD-9-CM diagnosis codes 410.X0 and 410.X1 or DRG codes 121, 122, and 123). Hospital records for these episodes were reviewed by trained abstractors using World Health Organization criteria for diagnosing AMI. We then calculated the positive predictive value of Medicare claims-based definitions of AMI. RESULTS: Of 2200 hospitalization episodes with Medicare diagnosis codes suggestive of AMI, 2022 hospital records (91.9%) were obtained. The positive predictive value for a primary Medicare claims-based definition was 94.1% (95% CI, 93.0%-95.2%). Positive predictive values for alternative claims-based definitions ranged slightly, with the definition including DRG codes and length-of-stay restrictions yielding the highest positive predictive value, 95.4% (95% CI, 94.3%-96.4%). Subjects with a history of myocardial infarction had a significantly lower positive predictive value than subjects without a history of myocardial infarction (88.1% vs 94.6%, P <.001). CONCLUSIONS: In this study, we observed high positive predictive values for a Medicare claims-based diagnosis of AMI and a diagnosis based on structured hospital record review.

Aged↗

Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction.

BACKGROUND: Despite improved laboratory assays for cardiac markers and a revised standard for definition of myocardial infarction (AMI), early detection of coronary ischemia in unselected patients with chest pain remains a difficult challenge. METHODS: Rapid measurements of troponin I (TnI), creatine kinase MB (CK-MB), and myoglobin were performed in 197 consecutive patients with chest pain and a nondiagnostic electrocardiogram for AMI. The early diagnostic performances of these markers and different multimarker strategies were evaluated and compared. Diagnosis of AMI was based on European Society of Cardiology/American College of Cardiology criteria. RESULTS: At a given specificity of 95%, TnI yielded the highest sensitivity of all markers at all time points. A TnI cutoff corresponding to the 10% coefficient of variation (0.1 microg/L) demonstrated a cumulative sensitivity of 93% with a corresponding specificity of 81% at 2 hours. The sensitivity was considerably higher compared to CK-MB and myoglobin, even considering patients with a short delay until admission. Using the 99th percentile of TnI results as a cutoff (0.07 microg/L) produced a cumulative sensitivity of 98% at 2 hours, but its usefulness was limited due to low specificities. Multimarker strategies including TnI and/or myoglobin did not provide a superior overall diagnostic performance compared to TnI using the 0.1 microg/L cutoff. CONCLUSION: A TnI cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of AMI. A lower TnI cutoff may be useful for very early exclusion of AMI. CK-MB and in particular myoglobin did not offer additional diagnostic value.

Aged↗

Indications for angiography subsequent to coronary artery bypass grafting.

BACKGROUND: Postoperative myocardial infarction is a rare, but potentially severe complication after coronary artery bypass grafting (CABG). Early markers for coronary bypass graft failure or native vessel occlusion are required, because immediate intervention could prevent major myocardial damage. METHODS: One thousand patients with coronary artery disease consecutively underwent CABG. Postoperative coronary angiography was performed in 40 patients with suspected myocardial ischemia. Creatine kinase (CK), CK-MB, leukocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), and glutamate-oxalacetate transaminase (GOT) were assessed at 0, 6, 12, 24, 48, and 72 hours after CABG as well as 12-lead standard electrocardiography (ECG). RESULTS: Postoperative angiography of 40 patients with suspected myocardial infarction revealed graft failure or occluded native vessels in 13 (32.5%) individuals. Patients with graft or vessel occlusion presented elevated (P < .005) leukocyte counts (17,215 +/- 6632 vs 10,773 +/- 3902 G/L) immediately after CABG. CK-MB concentrations differed ( P < .05) at 6 hours after CABG (54 +/- 48 vs 30 +/- 18 U/L). CK, CRP, LDH, and GOT did not show any differences between both groups. Frequency of ECG ST-segment elevation was increased (P < .05) in ischemic patients (69.2% vs 29.6%). CONCLUSIONS: Common signs of myocardial ischemia usually allow to diagnose unstable angina or myocardial infarction under native conditions. In contrast, these criteria frequently fail after CABG. Combined diagnostic criteria of elevated leukocytes (>14,000 G/L, at hour 0) and either ST elevation or CK-MB concentrations >35 U/L (at hour 6) at least seem to be very useful in detecting myocardial infarction after bypass grafting. In parallel, CK-MB elevation (>70 U/L, at hour 6) alone seems to predict ischemia. Both criteria should indicate angiography and potential revascularization. If these conditions were not fulfilled, the risk of perioperative myocardial infarction appears to be moderate.

Aged↗

Left ventricular ejection fraction to predict early mortality in patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Improvement in risk stratification of patients with non-ST-segment elevation acute coronary syndrome (ACS) is a gateway to a more judicious treatment. This study examines whether the routine determination of left ventricular ejection fraction (EF) adds significant prognostic information to currently recommended stratifiers. METHODS: Several predictors of inhospital mortality were prospectively characterized in a registry study of 1104 consecutive patients, for whom an EF was determined, who were admitted for an ACS. Multiple regression models were constructed using currently recommended clinical, electrocardiographic, and blood marker stratifiers, and values of EF were incorporated into the models. RESULTS: Age, ST-segment shifts, elevation of cardiac markers, and the Thrombolysis in Myocardial Infarction (TIMI) risk score all predicted mortality (P < .0001). Adding EF into the model improved the prediction of mortality (C statistic 0.73 vs 0.67). The odds of death increased by a factor of 1.042 for each 1% decrement in EF. By receiver operating curves, an EF cutoff of 48% provided the best predictive value. Mortality rates were 3.3 times higher within each TIMI risk score stratum in patients with an EF of 48% or lower as compared with those with higher. CONCLUSIONS: The TIMI risk score predicts inhospital mortality in a broad population of patients with ACS. The further consideration of EF adds significant prognostic information.

Acute Disease↗

Elevated creatine kinase-MB with normal creatine kinase predicts worse outcomes in patients with acute coronary syndromes: results from 4 large clinical trials.

BACKGROUND: The degree to which elevated creatine kinase (CK)-MB in the presence of normal CK is predictive of outcome is not well understood despite having been studied for decades. This analysis examined whether normal CK with elevated CK-MB in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) is an independent predictor of worse outcomes. A concomitant goal was to contribute insight to the debate over how patients with NSTE ACS should be managed. METHODS: Data for 25,960 patients from the GUSTO IIb, PARAGON A and B, and PURSUIT trials were analyzed. Of these patients, 6402 were excluded from primary analysis because of missing (unmeasured) biomarkers. Patients with complete laboratory data (n = 19,558) were grouped by CK and CK-MB results. To confirm the primary analysis results, data from patients with missing biomarkers were used in an imputation model. RESULTS: Patients were categorized in 1 of 4 groups: normal CK + normal CK-MB; normal CK + elevated CK-MB; elevated CK + normal CK-MB; or elevated CK + elevated CK-MB. For the primary outcome, 180-day death, or myocardial infarction, Kaplan-Meier estimates were 14.9%, 20.8%, 14.5%, and 18.2%, respectively. Regardless of total CK, elevated CK-MB was associated with a 25% to 49% increased relative risk of worse outcomes. Findings from the analyses were verified by the multivariable model. CONCLUSIONS: CK-MB remains a reliable marker for myocardial necrosis and a strong predictor of worse prognosis. All patients with ACS should have CK-MB measurement to search for cardiac ischemia. Patients with elevated CK-MB should receive aggressive management commensurate with their increased risks.

Acute Disease↗

The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE).

BACKGROUND: The impact and prognostic value of the redefinition of myocardial infarction (MI) with more sensitive markers have not been evaluated prospectively in a large, less selected population with acute coronary syndrome (ACS). METHODS: We evaluated the attack and case-fatality rates of MI based on initial and/or peak creatine kinase (CK), creatine kinase-MB (CK-MB), and cardiac troponin (the upper limit of normal [ULN] was defined according to the local hospital's standard) in a prospective observational registry of 26,267 patients with ACS admitted to 106 hospitals in 14 countries. RESULTS: The addition of cardiac troponin-positive status to CK status as a criterion for the diagnosis of MI resulted in as many as 1 in 4 additional patients meeting the redefined criteria. Compared with patients without elevated levels of CK and cardiac troponin, the crude odds for dying during hospitalization were significantly higher for patients with elevated troponin but not CK levels of greater than or equal to the ULN (odds ratio [OR] 2.2, 95% CI 1.6-2.9), those without CK levels >2 times the ULN (OR 2.8, 95% CI 2.2-3.5), and those with nonelevated levels of CK-MB (OR 2.1, 95% CI 1.4-3.2). The addition of cardiac troponin-positive status significantly increased the multivariable-adjusted odds for hospital death in patients with CK < or =2 times the ULN (OR 1.6, 95% CI 1.2-2.1) but not for patients without elevated levels of CK or CK-MB. CONCLUSIONS: The prognostic value of cardiac troponin, beyond that supplied by CK status or important baseline characteristics, assists in the identification of patients with ACS who are at increased risk for death.

Aged↗

Effects of tirofiban plus clopidogrel versus clopidogrel plus provisional abciximab on biomarkers of myocardial necrosis in patients with non-ST-elevation acute coronary syndromes treated with early aggressive approach. Results of the CLOpidogrel, upstream TIrofiban, in cath Lab Downstream Abciximab (CLOTILDA) study.

BACKGROUND: In non-ST-elevation acute coronary syndromes (NSTE-ACS), a strong correlation between adverse clinical events and peak values of myocardial necrosis markers has been found. In this study, we evaluated whether the adjunctive treatment with upstream tirofiban reduces the peak levels of cardiac troponin I and creatine kinase-MB (CK-MB) fraction in patients with NSTE-ACS undergoing early invasive strategy and pretreated with aspirin, heparin, and clopidogrel. METHODS: A total of 300 patients were randomized to receive tirofiban (group 1) or not (group 2). Serial marker samples were collected before and after coronary angiography in all cases and after percutaneous coronary intervention (PCI) when performed. RESULTS: Between the 2 groups, no differences were observed in clinical and angiographic findings. Percutaneous coronary intervention was globally performed in 198 patients (66%). Of 99 group 2 patients, 26 (26%) received abciximab just before PCI. No significant differences between the 2 groups were observed with regard to cardiac troponin I and CK-MB values at admission and at 6, 12, and 24 hours thereafter; peak values before coronary angiography; and peak values of index event. In addition, the cumulative biomarkers release of the index event was similar between the 2 groups. Major bleeding rate was 2% in group 1 and 1% in group 2 (P = not significant). Composite incidence of death, myocardial infarction, or rehospitalization for ACS at 30 days was 9% in group 1 and 10% in group 2. CONCLUSIONS: In patients with NSTE-ACS undergoing early invasive strategy, the adjunctive administration of upstream tirofiban did not reduce the peak values and the cumulative release of myocardial necrosis markers, compared with aspirin, heparin, and clopidogrel given on admission and associated with selective use of abciximab just before PCI.

Abciximab↗

Concerning the mechanism of pexelizumab's benefit in acute myocardial infarction.

BACKGROUND: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial previously demonstrated an unexpected dose-dependent reduction in 90-day mortality after bolus/infusion of pexelizumab despite no reduction in the primary end point of myocardial infarction (MI) size. We examined whether the mortality benefit was related to established modulators of clinical benefit such as baseline demographics, time to treatment from symptom onset, myocardial perfusion post-percutaneous coronary intervention (PCI), and extent of ST resolution. METHODS AND RESULTS: Eight hundred fourteen patients were randomized into 3 groups; (1) placebo, (2) pexelizumab bolus 2.0 mg/kg and placebo infusion for 20 hours, and (3) pexelizumab bolus 2.0 and 0.05 mg/kg per hour infusion for 20 hours commencing 4 hours after the bolus. Subjects presented with ST elevation MI within 6 hours of symptom onset and underwent PCI, creatine kinase (CK), and CK-MB measurements taken sequentially to define CK-MB area under the curve (AUC) and sequential ECG's defined ST resolution and QRS infarct size. Whereas mortality for both placebo and bolus pexelizumab groups rose during later time after presentation, it remained low and did not change appreciably during the 6-hour randomization window when patients received pexelizumab bolus infusion. Amplification of the mortality benefit was evident in patients with the highest quartile of hemodynamic compromise, that is, heart rate > or = 90 beat/min and systolic blood pressure < or = 118 mm Hg (3.2% vs 11.3% P = .004). A significant interaction between treatment assignment and hemodynamic status (P = .013) existed after adjusting for age, race, and MI location. Clinical benefit was not related to infarct size, extent of ST elevation, or evidence of angiographic or electrocardiographic reperfusion. CONCLUSIONS: These data raise the possibility that the clinical benefit of pexelizumab is mediated through novel pathways such as reduction in apoptosis or other mechanisms.

Adolescent↗