Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials.

BACKGROUND: Unfractionated heparin has been the primary anticoagulant therapy for percutaneous coronary intervention for >20 years. Despite the availability of rapid "point of care" testing, little clinical data defining the optimal level of anticoagulation are available. Furthermore, recent reports have advocated the use of low-dose heparin regimens in the absence of large-scale, well-conducted studies to support this practice. METHODS AND RESULTS: We pooled the data from 6 randomized, controlled trials of novel adjunctive antithrombotic regimens for percutaneous coronary interventions in which unfractionated heparin constituted the control arm. Patients were divided into 25-s intervals of activated clotting times (ACTs), from <275 s to >476 s. In a total of 5216 patients, the incidence of death, myocardial infarction, or any revascularization and major or minor bleeding at 7 days were calculated for each group and compared. An ACT in the range of 350 to 375 s provided the lowest composite ischemic event rate of 6.6%, or a 34% relative risk reduction in 7-day ischemic events compared with rates observed between 171 and 295 s by quartile analysis (P=0.001). CONCLUSIONS: Contrary to recent reports, the optimal suppression of ischemic events with unfractionated heparin therapy in patients undergoing percutaneous coronary intervention demands treatment to ACT levels that are substantially higher than currently appreciated. These data define a goal for heparin dosing within coronary interventions and establish a benchmark of optimal unfractionated heparin therapy against which future trials of novel antithrombotic regimens in percutaneous interventions can be compared.

beta-blockers before percutaneous coronary intervention do not attenuate postprocedural creatine kinase isoenzyme rise.

BACKGROUND: beta-blocker (BB) use reduces infarct size in spontaneously occurring nonreperfused infarcts but probably does not change infarct size in patients treated with reperfusion therapy. A recent observational study suggested that BB use concurrent with percutaneous coronary intervention (PCI) decreased the risk of creatine kinase (CK)-MB elevation. The cogency of such a conclusion is dependent on the ability to risk-adjust for the multiple differences in patients treated with and without BBs. METHODS AND RESULTS: Using propensity score and multivariate regression analyses, 6200 consecutive patients were analyzed to assess the relationship between BB use before PCI and per protocol-measured CK and CK-MB rise. There were several highly significant (P<0.001) differences between patients with and without BB treatment (eg, age, prior infarction, unstable angina). Maximum CK and CK-MB levels were higher in patients taking BBs (CK median, 95 U [interquartile range: 61, 175]; CK-MB, 3 U [2, 5]) than in patients not taking BBs (CK, 91 U [60, 157]; CK-MB, 3 U [2, 4]) (P=0.011 and P=0.021 for CK and CK-MB, respectively). After adjustment for significant differences in baseline characteristics there was no difference in either maximum CK rise (P=0.21) or maximum CK-MB rise (P=0.99). CONCLUSIONS: The results of this large observation study do not support the contention that BB use before PCI decreases myocardial injury.

Pronounced benefit of coronary stenting and adjunctive platelet glycoprotein IIb/IIIa inhibition in complex atherosclerotic lesions.

BACKGROUND: Previous trials testing stents compared with balloon angioplasty excluded patients with complex lesions and did not assess the effect of adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the effect of stenting and abciximab specifically for patients with complex lesions. METHODS AND RESULTS: Patients with complex lesions (long, tandem, severely calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations; saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were included in the analysis. The 1-year combined death or myocardial infarction rates in the 4 treatment groups were as follows: balloon angioplasty/placebo, 14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%, respectively (P=0.03). The incidence of target vessel revascularization at 1 year was 30.5%, 18.0%, 24.4%, and 19.7% in the 4 groups, respectively (P<0.001). After adjustment for baseline differences, multivariate analysis demonstrated that the rate of death or myocardial infarction was independently reduced by balloon angioplasty/abciximab (hazard ratio, 0.51; P<0.001) and stent/abciximab (hazard ratio, 0.60; P=0.02) but was not affected by the use of stents alone. Conversely, target vessel revascularization was reduced by stent/placebo (hazard ratio, 0.53; P<0.001), stent/abciximab (hazard ratio, 0.58; P<0.001), and balloon angioplasty/abciximab (hazard ratio, 0.74; P=0.006) compared with balloon angioplasty/placebo, respectively. CONCLUSIONS: The combination of stenting and abciximab during percutaneous coronary interventions for patients with angiographically complex lesions confers additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization.

Progression of aortic stenosis in 394 patients: relation to changes in myocardial and mitral valve dysfunction.

OBJECTIVES: This study reports the results of echocardiographic follow-up in a large cohort of patients with aortic stenosis and correlates the progression of aortic stenosis with changes in the degree of mitral regurgitation and left ventricular hypertrophy and systolic dysfunction. BACKGROUND: Progressive aortic stenosis often causes left ventricular dysfunction and mitral regurgitation. Doppler echocardiography has greatly assisted in the noninvasive evaluation and follow-up of aortic stenosis. Nevertheless, the longitudinal follow-up of patients with Doppler echocardiography for the progression of aortic stenosis and the significance of progressive ventricular hypertrophy and mitral regurgitation have not been reported. METHODS: Serial Doppler echocardiography was performed in 394 consecutive patients with valvular aortic stenosis at baseline and after a mean follow-up period of 37 +/- 16 months. Mean and peak aortic gradients, aortic valve area, left ventricular systolic and diastolic diameters and percent area change (shortening fraction) were expressed as continuous variables, and systolic dysfunction, mitral regurgitation, ventricular hypertrophy and filling properties were tabulated as categoric variables using a semiquantitative grading system. RESULTS: Peak and mean gradients increased by an average of 8.3 and 6.3 mm Hg/year, respectively; end-systolic and end-diastolic diameters increased by 1.9 and 1.6 mm/year, respectively; and aortic valve area decreased by 0.14 cm2/year during the follow-up interval (p < 0.001 for all), indicating progression of aortic stenosis and ventricular dilation. Patients in the lowest quartile of aortic valve area and highest quartiles of mean and peak gradients had the least change compared with those in the highest quartile of aortic valve area and lowest quartile of mean and peak gradients (p < 0.01 for all). Patients with more mitral regurgitation at follow-up than at baseline had higher mean percent increase in mean and peak gradients as well as more progression of ventricular dilation and worsening systolic function compared with those with stable or improving mitral regurgitation (p < 0.05 for all). Similarly, subjects with worsening left ventricular hypertrophy had larger mean percent increase in mean and peak gradients than those with stable left ventricular hypertrophy (p < 0.01) but maintained stable ventricular volumes and systolic function. There was no correlation between the amount of change in mean or peak gradients and degree of deterioration in systolic function. CONCLUSIONS: Aortic stenosis progresses predictably over time; however, systolic dysfunction is an inconsistent marker of the hemodynamic consequences of severe aortic stenosis. As an adaptive response to pressure overload, progressive hypertrophy appears to prevent ventricular dilation and development or worsening of mitral regurgitation. Conversely, progressive mitral regurgitation may be seen as a maladaptive consequence of increasing aortic stenosis.

Does coronary angiography before emergency aortic surgery affect in-hospital mortality?

OBJECTIVES: To study the relationship between coronary angiography and in-hospital mortality in patients undergoing emergency surgery of the aorta without a history of coronary revascularization or coronary angiography before the onset of symptoms. BACKGROUND: In the setting of acute ascending aortic dissection warranting emergency aortic repair, coronary angiography has been considered to be desirable, if not essential. The benefits of defining coronary anatomy have to be weighed against the risks of additional delay before surgical intervention. METHODS: Retrospective analysis of patient charts and the Cardiovascular Information Registry (CVIR) at the Cleveland Clinic Foundation. RESULTS: We studied 122 patients who underwent emergency surgery of the aorta between January 1982 and December 1997. Overall, in-hospital mortality was 18.0%, and there was no significant difference between those who had coronary angiography on the day of surgery compared with those who had not (No: 16%, n = 81 vs. Yes: 22%, n = 41, p = 0.46). Multivariate analysis revealed that a history of myocardial infarction (MI) was the only predictor of in-hospital mortality (relative risk: 4.98 95% confidence interval: 1.48-16.75, p = 0.009); however, coronary angiography had no impact on in-hospital mortality in patients with a history of MI. Furthermore, coronary angiography did not significantly affect the incidence of coronary artery bypass grafting (CABG) during aortic surgery (17% vs. 25%, Yes vs. No). Operative reports revealed that 74% of all CABG procedures were performed because of coronary dissection, and not coronary artery disease. CONCLUSIONS: These data indicate that determination of coronary anatomy may not impact on survival in patients undergoing emergency surgery of the aorta and support the concept that once diagnosed, patients should proceed as quickly as possible to surgery.

Atenolol use and clinical outcomes after thrombolysis for acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries.

OBJECTIVES: We assessed the use and effects of acute intravenous and later oral atenolol treatment in a prospectively planned post hoc analysis of the GUSTO-I dataset. BACKGROUND: Early intravenous beta blockade is generally recommended after myocardial infarction, especially for patients with tachycardia and/or hypertension and those without heart failure. METHODS: Besides one of four thrombolytic strategies, patients without hypotension, bradycardia or signs of heart failure were to receive atenolol 5 mg intravenously as soon as possible, another 5 mg intravenously 10 min later and 50 to 100 mg orally daily during hospitalization. We compared the 30-day mortality of patients given no atenolol (n=10,073), any atenolol (n=30,771), any intravenous atenolol (n=18,200), only oral atenolol (n=12,545) and both intravenous and oral drug (n=16,406), after controlling for baseline differences and for early deaths (before oral atenolol could be given). RESULTS: Patients given any atenolol had a lower baseline risk than those not given atenolol. Adjusted 30-day mortality was significantly lower in atenolol-treated patients, but patients treated with intravenous and oral atenolol treatment vs. oral treatment alone were more likely to die (odds ratio, 1.3; 95% confidence interval, 1.0 to 1.5; p=0.02). Subgroups had similar rates of stroke, intracranial hemorrhage and reinfarction, but intravenous atenolol use was associated with more heart failure, shock, recurrent ischemia and pacemaker use than oral atenolol use. CONCLUSIONS: Although atenolol appears to improve outcomes after thrombolysis for myocardial infarction, early intravenous atenolol seems of limited value. The best approach for most patients may be to begin oral atenolol once stable.

Comparison of stenting and balloon angioplasty for narrowings in aortocoronary saphenous vein conduits in place for more than five years.

To compare the 1 year outcome of Palmaz-Schatz stent implantation versus balloon angioplasty for treatment of obstructive lesions in saphenous vein grafts, we combined databases from the Palmaz-Schatz vein graft stent registry and the coronary angioplasty arm of the Coronary Angioplasty Versus Excisional Atherectomy Trial II (CAVEAT II) for comparison of baseline characteristics, procedural variables, in-hospital events and 1-year composite end point of death, Q-wave myocardial infarction, and repeat target vessel revascularization. De novo graft lesions not involving the ostia were treated with stent implantation in 377 patients and with coronary angioplasty in 156 patients. The patients were comparable in age, coronary risk profile, interval from bypass surgery (9 +/- 4 years), and reference vessel diameter. The in-hospital composite end point of death, myocardial infarction, and emergency revascularization was lower in the stent group (10%) than in the angioplasty cohort (17%) (p = 0.059). At 1 year, the patients in the stent group had a markedly lower incidence of the composite end point of death, myocardial infarction, or revascularization (23% vs 45%, p <0.001). In this nonrandomized comparison with balloon angioplasty, the treatment of lesions in saphenous vein grafts appears to be favorably influenced by Palmaz-Schatz stent implantation, in terms of in-hospital events and clinical restenosis at 1 year follow-up.

Factors leading to progression of valvular aortic stenosis.

The rate of progression of aortic stenosis (AS) in adults is variable. To determine whether clinical or echocardiographic variables are associated with more rapid hemodynamic progression, we identified 91 AS patients (initial valve area < or = 2.0 cm2) with 2 technically adequate studies separated by > or = 6 months. From the first study, left ventricular dimensions and AS severity were measured by standard Doppler-echocardiographic methods. Each aortic valve was graded for severity of calcification and degree of restricted leaflet motion; the sum of these grades provided a severity index reflecting leaflet pathology. Clinical and electrocardiographic variables were abstracted from medical records. Mean age was 68 years (range 29 to 89) and 61 were women. Initial AS severity ranged from an aortic valve area of 0.6 to 2.0 cm2 (median 1.3 cm2). During a mean follow-up of 1.8 years the aortic valve area decreased 0.04 cm2/year. The patient group with more rapid progression (decrease in aortic valve area > or = 0.1 cm2/year) had a larger proportion of men (p <0.01) and patients with an elevated serum creatinine (p = 0.04), a higher left ventricular mass index (p = 0.01), and a higher severity index (p <0.001). Multivariable regression analysis identified the severity index (direct relation) and the initial aortic valve area (inverse relation) as the only independent variables associated with more rapid progression. In conclusion, the rate of AS progression, although highly variable, is more rapid when leaflet calcification is more marked.

Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease.

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as > or = 1 stenosis of > or = 50% in a major epicardial artery or its main branches; severe coronary disease was defined as > or = 50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with > or = 70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.

Late myocardial ischemic events after saphenous vein graft intervention--importance of initially "nonsignificant" vein graft lesions.

Patients undergoing percutaneous coronary revascularization (PCR) for narrowed saphenous vein grafts (SVGs) have a high incidence of subsequent cardiac events, but the relative contribution of treated and untreated SVGs, and of native coronary narrowings to late events is uncertain. This study evaluated the role of progression of SVG disease at untreated sites to cardiac events in these patients. All patients with successful PCR of SVG lesions who were enrolled in clinical trials with mandated repeat angiography from 1990 to 1994 were studied. One hundred three patients (age 63 +/- 8 years, 82% men, ejection fraction 54 +/- 12%, graft age 8 +/- 4 years), contributing 1,095 analyzable 15- to 25-mm SVG segments were followed 29 +/- 13 months (4 patients were lost to follow-up). Actuarial event-free (death, myocardial infarction, bypass surgery, or PCR) and overall survival at 12 months were 47 +/- 5% and 94 +/- 2%, respectively. Fifty-six percent of all early (< or = 12 months) events resulted from ischemia from recurrence at initially treated SVG sites, 26% at nontreated SVG sites, and 14% at nontreated native coronary sites. By 36 months, event-free and overall survival were 25 +/- 6% and 86 +/- 4%, respectively. Events occurring > 12 months after initial treatment resulted most frequently from ischemia from progression of narrowing at untreated SVG sites (46%). Ischemic events from initially untreated SVG sites were correlated with initial percent stenosis (initial, 41% to 50%; 45% events, 31% to 40%; 18% events, < or = 30%; 2% events, p <0.001) and reference SVG diameter (p = 0.003). Recurrent ischemic events from initially treated SVG sites were independently correlated with initial percent stenosis (initial > 75%; 43% events, 50% to 75%; 27% events, < 50%; 18% events, p = 0.01), but not with final percent stenosis. The frequent occurrence of events from nontreated 41% to 50% stenoses suggests a need for increased surveillance in patients with these lesions. The low incidence of events from initially treated lesions < 50% suggests that the hypothesis that "nonsignificant" 41% to 50% lesions might best be treated at the time other more severe narrowings are treated should be examined.

A comparison of debulking versus dilatation of bifurcation coronary arterial narrowings (from the CAVEAT I Trial). Coronary Angioplasty Versus Excisional Atherectomy Trial-I.

We compared the effectiveness of percutaneous transluminal coronary angioplasty and directional coronary atherectomy for the management of bifurcation coronary lesions in 1,012 patients enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial-I. Directional coronary atherectomy was associated with less angiographic residual stenosis, but with a higher rate of side-branch closure and non-Q-wave myocardial infarction.

The benefit of abciximab in percutaneous coronary revascularization is not device-specific.

Abciximab has been shown to decrease adverse outcomes after percutaneous coronary interventions, but it is unclear whether this beneficial effect is more or less pronounced with specific devices. This study sought to determine the relative magnitude of the benefit of abciximab among different interventional devices. Data from the 5 placebo-controlled trials of abciximab during coronary intervention were pooled. Patients were divided into groups based on whether they received balloon angioplasty alone, elective stenting, bailout stenting, or directional coronary atherectomy. In the patients undergoing balloon angioplasty, the 30-day hazard ratio for death or myocardial infarction (MI) in the group randomized to abciximab versus the placebo-treated group was 0.52 (p <0.001), for elective stenting the hazard ratio was 0.51 (p <0.001), for bailout stenting the hazard ratio was 0.38 (p <0.001), and for directional coronary atherectomy the hazard ratio was 0.38 (p = 0.007). A Cox proportional-hazards model revealed that overall, the use of abciximab decreased the composite end point of 30-day death or MI rates (hazard ratio 0.55, 95% confidence interval 0.43 to 0.69, p <0. 001). However, bailout stenting and directional coronary atherectomy were associated with increased rates of death or MI compared with balloon angioplasty, as was elective stenting in women compared with men. There was no significant increase in major bleeding episodes associated with abciximab in any of the device categories. These findings from all the controlled coronary revascularization trials using abciximab demonstrate that a decrease in death and MI is achieved with abciximab regardless of the type of device used, without an increase in significant bleeding complications.

Effect of abciximab on the pattern of reperfusion in patients with acute myocardial infarction treated with primary angioplasty. RAPPORT investigators. ReoPro And Primary PTCA Organization and Randomized Trial.

We investigated the effect of platelet fibrinogen receptor blockade on infarct size after primary angioplasty. Abciximab significantly reduced the time-to-peak creatine kinase without affecting enzymatic infarct size, suggesting a beneficial effect on the pattern and speed of reperfusion.

Predictors and prognosis of suboptimal coronary blood flow after primary coronary angioplasty in patients with acute myocardial infarction.

We hypothesized that certain clinical and angiographic characteristics on presentation predict suboptimal infarct artery flow after percutaneous intervention during acute myocardial infarction (AMI). The goal of angioplasty (percutaneous transluminal coronary angioplasty [PTCA]) during AMI is the prompt restoration of normal flow to achieve myocardial reperfusion. However, inadequate epicardial coronary flow is observed in 10% to 20% of patients. From 2 large randomized trials-Global Use of Strategies To open Occluded arteries in Acute Coronary Syndromes-IIb, and Randomized Placebo-Controlled Trial of Platelet glycoprotein IIb/IIIa Blockade With Primary Angioplasty for Acute Myocardial Infarction-patients undergoing primary PTCA during AMI were included in the analysis. A multivariate logistic model was used to identify factors associated with final Thrombolysis In Myocardial Infarction (TIMI) flow grade < or =2. The 891 patients were aged (mean +/- SD) 61 +/- 12 years, 75% were men, and 39% had an anterior wall AMI. Patients underwent PTCA within 4.8 +/- 3.2 hours from the onset of chest pain. The incidence of final TIMI 3 flow was 81%. TIMI flow grade < or =2 was independently associated with increasing age (odds ratio [OR] 1.39 for every 10 years, 95% confidence interval [CI] 1.19 to 1.62), increasing heart rate (OR 1.16 for every 10 beats, 95% CI 1.05 to 1.28), and presence of visible thrombus on baseline angiogram (OR 1.89, 95% CI 1.18 to 3.05). Conversely, baseline TIMI 2 or 3 flow grade (OR 0.46, 95% CI 0.28 to 0.75) and left circumflex intervention (OR 0.42, 95% CI 0.23 to 0.79) correlated with normal postprocedural coronary flow. Mortality was significantly higher in patients with TIMI < or =2 than TIMI 3 flow grade (10.2% vs 1.5%, p <0.001, respectively). Thus, angiographic evidence of thrombus and 2 pivotal clinical characteristics, advanced age and elevated heart rate, predict lack of adequate coronary reperfusion. Conversely, the presence of normal or near-normal coronary flow before intervention correlates with a good angiographic result. Mortality risk is increased in patients with postprocedural suboptimal angiographic coronary flow.

A profile of candidates for repeat myocardial revascularization: implications for selection of treatment.

OBJECTIVES: It is not known whether the results of randomized trials comparing coronary artery bypass grafting to percutaneous transluminal coronary angioplasty for initial revascularization apply to repeat revascularization in patients with prior bypass grafts. We studied the differences between the patients with prior bypass grafts referred for surgery or angioplasty to identify the clinical and angiographic characteristics that correlated best with either choice and to find clues that might aid in selecting one treatment over the other. METHODS: Between 1992 and 1994, 870 patients underwent first isolated reoperation and 793 patients underwent first balloon angioplasty after a previous operation. A jeopardy score (0 to 8 points) was derived for each patient on the basis of the relative size of the ischemic territory. Clinical and angiographic data were analyzed for association with the revascularization strategy. RESULTS: The following characteristics were more prevalent in the reoperation group: male sex, diabetes, hypertension, valvular disease, normocholesterolemia, and severe left ventricular systolic dysfunction; fewer functioning venous and arterial grafts; and a higher jeopardy score (p < 0.01 for all) than in the angioplasty group. A higher jeopardy score, diabetes, and a lower number of functioning arterial or venous grafts were strong, independent predictors of referral for reoperation (p < 0.01 for all). In hospital death and Q-wave infarction (p < 0.01 for both) were more frequent in the reoperation group. CONCLUSIONS: Reoperation was the revascularization procedure of choice when larger regions of myocardium were in jeopardy. Angioplasty was more frequently chosen in the presence of a patent arterial graft to the left anterior descending coronary artery or multiple functioning bypass grafts. Reoperation was associated with a higher risk of in-hospital complications than angioplasty.

Unfractionated and low-molecular-weight heparins in acute coronary syndromes: current recommendations.

All patients with acute coronary syndromes and without obvious bleeding or acute cerebrovascular events are candidates for heparin therapy. This article is a review of the pharmacology of unfractionated and low-molecular-weight heparins, trials of heparin therapy in acute coronary syndromes, and recommendations for using these agents.

Angioplasty or fibrinolysis for acute MI? The GUSTO IIb study.

The angioplasty substudy of the GUSTO IIb trial confirmed that the short-term results of primary angioplasty are better than those of fibrinolytic therapy in patients with acute myocardial infarction (MI). In the largest and most rigorous study of this topic performed to date, 9.6% of patients who underwent primary angioplasty either died or suffered a disabling stroke or another myocardial infarction within 30 days, compared with 13.7% of patients who received fibrinolytic therapy, for an odds ratio of 0.67 (P = .033). This difference was less than in previous studies, possibly in part because fibrinolytic therapy has improved. The findings underscore the importance of promptly restoring complete, brisk, antegrade flow in the infarct-related artery, regardless of what treatment is used.

Frequency and long-term impact of myonecrosis after coronary stenting.

AIMS: To study the frequency of creatine kinase MB elevation in stent recipients and to correlate the magnitude of myonecrosis with long-term ischaemic events. METHODS AND RESULTS: We evaluated the frequency and impact (major adverse ischaemic events) of creatine kinase MB elevation in 3478 patients undergoing planned coronary stenting and divided them in five strata according to peak creatine kinase MB: normal, 1-3 x, 3-5 x, 5-10 x and >10 x above upper limit of normal. Graft intervention was done in 15% and 61% received platelet glycoprotein IIb/IIIa receptor inhibitors. The average follow-up period was 15+/-15 (range 1-72) months. Creatine kinase MB elevation above upper limit of normal occurred in 24% and in 5.3% it was greater than 5 x upper limit of normal. The unadjusted rates of actuarial mortality in the five strata were: 7.5% (198/2637), 8.0% (40/502), 11.0% (17/155), 10.8% (11/102) and 29.3% (24/82), respectively, P<0.001. Logistic regression analysis including 18 demographic and procedural variables revealed that, in addition to age, extent of coronary disease, ventricular function and coronary risk profile, creatine kinase MB elevation was associated with a significant increase in major ischaemic events at follow-up. The excess risk was concentrated mainly in the highest stratum of creatine kinase MB elevation. CONCLUSIONS: Thus, in the era of stenting and aggressive adjunctive pharmacology, peri-procedural myonecrosis still remains frequent and has an important impact on long-term event-free survival. Intensive efforts to reduce creatine kinase MB elevation after revascularization are warranted and should lead to important benefits.

Predictors of death and reinfarction at 30 days after primary angioplasty: the GUSTO IIb and RAPPORT trials.

BACKGROUND: Thirty-day death among recipients of fibrinolytic therapy for acute myocardial infarction (MI) is tightly correlated with easily obtainable key demographic and clinical parameters such as age, blood pressure, heart rate, and infarct location. Similar data for primary angioplasty are not available. METHODS AND RESULTS: Data from 2 large, contemporary, primary angioplasty trials were formally combined and analyzed with respect to death and death/repeat MI at 30 days through the use of multivariate logistic regression models. The 1048 patients had a median age of 62 years, and 26% were women. Thirty-eight percent had an anterior infarction. The patients underwent angioplasty at a median delay from symptom onset of 3.8 hours. Death was independently predicted by increasing age (adjusted odds ratio [OR] per decade 2.32, 95% confidence interval [CI] 1.60 to 3.42), whereas a history of smoking (OR 0.29, CI 0.13 to 0.64), Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after angioplasty (OR vs TIMI <3 0.21, CI 0.10 to 0.45) and higher systolic blood pressure (OR per 10 mm Hg 0.73, CI 0.62 to 0. 87) were associated with lower mortality rates. Death or repeat MI was independently associated with increasing age (OR per decade 1.40, CI 1.13 to 1.76) and anterior location of the index MI (OR 1.89, CI 1.12 to 3.20). TIMI grade 3 flow (OR vs TIMI <3 0.40, CI 0.23 to 0. 68) and higher systolic blood pressure (OR per 10 mm Hg 0.79, CI 0. 71 to 0.89) were associated with a lower incidence of death/repeat MI. Time to angioplasty, heart rate, extent of coronary artery disease, participation in 1 of the 2 trials, and all common coronary risk factors did not significantly predict outcome. CONCLUSIONS: Death and reinfarction after primary angioplasty are predominantly predicted by age, hemodynamic instability, and the attainment of TIMI 3 flow in the infarct artery.

Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators.

BACKGROUND: The benefit of catheter-based reperfusion for acute myocardial infarction (MI) is limited by a 5% to 15% incidence of in-hospital major ischemic events, usually caused by infarct artery reocclusion, and a 20% to 40% need for repeat percutaneous or surgical revascularization. Platelets play a key role in the process of early infarct artery reocclusion, but inhibition of aggregation via the glycoprotein IIb/IIIa receptor has not been prospectively evaluated in the setting of acute MI. METHODS AND RESULTS: Patients with acute MI of <12 hours' duration were randomized, on a double-blind basis, to placebo or abciximab if they were deemed candidates for primary PTCA. The primary efficacy end point was death, reinfarction, or any (urgent or elective) target vessel revascularization (TVR) at 6 months by intention-to-treat (ITT) analysis. Other key prespecified end points were early (7 and 30 days) death, reinfarction, or urgent TVR. The baseline clinical and angiographic variables of the 483 (242 placebo and 241 abciximab) patients were balanced. There was no difference in the incidence of the primary 6-month end point (ITT analysis) in the 2 groups (28.1% and 28.2%, P=0.97, of the placebo and abciximab patients, respectively). However, abciximab significantly reduced the incidence of death, reinfarction, or urgent TVR at all time points assessed (9.9% versus 3.3%, P=0.003, at 7 days; 11.2% versus 5.8%, P=0.03, at 30 days; and 17.8% versus 11.6%, P=0.05, at 6 months). Analysis by actual treatment with PTCA and study drug demonstrated a considerable effect of abciximab with respect to death or reinfarction: 4.7% versus 1.4%, P=0.047, at 7 days; 5.8% versus 3.2%, P=0.20, at 30 days; and 12.0% versus 6.9%, P=0.07, at 6 months. The need for unplanned, "bail-out" stenting was reduced by 42% in the abciximab group (20.4% versus 11.9%, P=0.008). Major bleeding occurred significantly more frequently in the abciximab group (16.6% versus 9.5%, P=0.02), mostly at the arterial access site. There was no intracranial hemorrhage in either group. CONCLUSIONS: Aggressive platelet inhibition with abciximab during primary PTCA for acute MI yielded a substantial reduction in the acute (30-day) phase for death, reinfarction, and urgent target vessel revascularization. However, the bleeding rates were excessive, and the 6-month primary end point, which included elective revascularization, was not favorably affected.