Search PubMed⌕ Search

Biomedical subjects

C M Gibson

Publications and source records attributed to C M Gibson.

At least 19 recordsLinked to original sources
PubMed2002

Determinants of improvement in epicardial flow and myocardial perfusion for ST elevation myocardial infarction; insights from TIMI 14 and InTIME-II.

BACKGROUND: When evaluating new reperfusion regimens for ST elevation MI, it is important to adjust for factors that influence the likelihood of achieving normal epicardial flow and complete ST resolution. METHODS AND RESULTS: A total of 610 patients from TIMI 14 contributed to the angiographic analyses. The electrocardiographic analyses were based on 544 patients from TIMI 14 and 763 patients from InTIME-II. For each hour from onset of symptoms to initiation of pharmacological reperfusion, the odds of achieving TIMI 3 flow at 90 min or complete ST resolution at 60-90 min decreased significantly (P=0.03). Anterior location of infarction was associated with a reduction in the odds of achieving TIMI 3 flow or complete ST resolution. The use of abciximab as part of the reperfusion regimen significantly increased the odds of TIMI 3 flow (P=0.01) and ST resolution (P<0.001). The fibrinolytic administered (alteplase, reteplase, lanoteplase) did not influence the odds of TIMI 3 flow or ST resolution after adjusting for time to treatment, infarct location, and use of abciximab. CONCLUSIONS: The influence of time from symptoms on epicardial flow and STRES reinforces the need for increased efforts to reduce treatment delays in patients with ST elevation MI. The significant benefits of abciximab with respect to facilitation of epicardial and myocardial reperfusion are evident even after adjusting for time to treatment and infarct location. To adjust for determinants of success of reperfusion regimens, phase II trials evaluating new drug combinations should consider using a randomization scheme that stratifies patients based on infarct location and time from symptoms.

Abciximab↗
PubMed2001

Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.

BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.

Antibodies, Monoclonal↗
PubMed2001

Safety of the weight-adjusted dosing regimen of tenecteplase in the ASSENT-Trial.

The results of the ASsessment of Safety and Efficacy of a New Thrombolytic agent (ASSENT-2) trial revealed that tenecteplase (TNK) is equivalent to tissue plasminogen activator (t-PA) for treating myocardial infarction. Because careful consideration of safety is important with all agents, including the newer bolus therapies, and across a range of doses, this study evaluated the safety of TNK compared with t-PA across a range of weight and dose categories. The 5 doses of TNK ranged from 30 to 50 mg and were adjusted for estimated weight. Rates of death and intracranial hemorrhage were determined among patients receiving TNK and t-PA in ASSENT-2, stratified by categories of estimated weight corresponding to each TNK dose. Respective rates of death with TNK versus t-PA were not significantly different in any estimated weight category: <60 kg (12.54% vs 11.46%), 60 to 69 kg (8.22% vs. 8.97%), 70 to 79 kg (5.57% vs 5.48%), 80 to 89 kg (4.66% vs 5.36%), and > or =90 kg (4.91% vs. 3.96%, all p > or =0.26). Respective rates of intracranial hemorrhage were also not significantly different: <60 kg (2.20% vs. 2.29%), 60 to 69 kg (0.97% vs. 1.33%), 70 to 79 kg (1.15% vs. 1.10%), 80 to 89 kg (0.73% vs 0.49%), and > or =90 kg (0.47% vs 0.47%, all p > or =0.33). Adjustment for small baseline differences in this randomized sample did not change the results. Thus, across the range of estimated weight categories corresponding to each TNK dose, TNK is as safe and effective as t-PA.

Aged↗
PubMed2001

Early coronary intervention following pharmacologic therapy for acute myocardial infarction (the combined TIMI 10B-TIMI 14 experience).

Earlier studies have suggested that immediate percutaneous coronary intervention (PCI) following thrombolytic therapy for acute myocardial infarction (AMI) is associated with an increase in adverse events and that routine PCI in this setting has offered no advantage over a conservative strategy. To reassess this issue in a more recent era, we evaluated 1,938 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B and 14 trials of AMI. Patients in TIMI 10B were randomized to receive tissue plasminogen activator or TNK tissue plasminogen activator, whereas patients in TIMI 14B trial were randomized to receive thrombolytic therapy with or without abciximab. All patients underwent angiography 90 minutes after receiving pharmacologic therapy. Patients who underwent PCI were classified as having undergone a rescue procedure (TIMI 0 or 1 flow at 90 minutes), an adjunctive procedure (TIMI 2 or 3 flow at 90 minutes), or a delayed procedure (performed >150 minutes after symptom onset, median of 2.75 days). Among patients with TIMI 0 or 1 flow, there was a trend for lower 30-day mortality among patients who underwent rescue PCI than among those who did not (6% vs 17%, p = 0.01, adjusted p = 0.28). Patients who underwent adjunctive PCI had similar 30-day mortality and/or reinfarction as those who underwent delayed PCI. In a multivariate model both had lower 30-day mortality and/or reinfarction than patients with "successful thrombolysis" (i.e., TIMI 3 flow at 90 minutes) who did not undergo revascularization (p = 0.02). Thus, early PCI following AMI is associated with excellent outcomes. Randomized trials of an early invasive strategy following thrombolysis are warranted.

Abciximab↗
PubMed2001

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.

Aged↗
PubMed2001

Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.

BACKGROUND: There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. METHODS: We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. RESULTS: At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). CONCLUSIONS: In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.

Aged↗
PubMed2001

Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy.

BACKGROUND: Use of abciximab in combination with administration of thrombolytics has been shown to improve epicardial and microvascular coronary blood flow in acute myocardial infarction (AMI). As a potential mechanism, we hypothesized that combination therapy would reduce angiographically evident thrombus (AET) and would increase lumen diameter compared with thrombolytic monotherapy. METHODS AND RESULTS: Patients who received combination therapy in TIMI 14 (low-dose thrombolytic plus abciximab, n=732) were compared with patients who received thrombolytic monotherapy without abciximab in the TIMI 4, 10A, 10B, and 14 trials (n=1662). Thrombus burden was assessed 90 minutes after treatment, and quantitative angiography was performed in an angiographic core laboratory by investigators blinded to treatment assignment. The frequency of AET was reduced in patients who received abciximab combination therapy compared with thrombolytic monotherapy (26.6% versus 35.4%, P<0.001). Similar findings were observed when the analysis was restricted to patients with patent arteries (14.7% versus 20.8%, P=0.001). Residual percent diameter stenosis at 90 minutes was also improved in the abciximab therapy group both in patent arteries (64.6+/-16.6 versus 68.3+/-14.8, P<0.001) and between patent and occluded arteries (69.3+/-19.5 versus 73.8+/-17.9, P<0.001). The absence of AET was associated with an increased frequency of >70% ST-segment resolution by 90 minutes (37.2%, 110/296 versus 18.9%, 54/286, P<0.001). CONCLUSIONS: Compared with thrombolytic monotherapy, combination therapy with abciximab reduces AET, which in turn is associated with reduced residual stenosis and improved ST-segment resolution in AMI. These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI.

Abciximab↗
PubMed2001

Can we replace the 90-minute thrombolysis in myocardial infarction (TIMI) flow grades with those at 60 minutes as a primary end point in thrombolytic trials? TIMI Study Group.

The establishment of patency (Thrombolysis In Myocardial Infarction [TIMI] grade 2 or 3 flow) and/or TIMI grade 3 flow at 60 minutes after thrombolytic administration is both a univariate and multivariate predictor of in-hospital and 30-day mortality, and the odds ratios for mortality are nearly identical for TIMI grade 3 flow at 60 and 90 minutes. Thus, the 60-minute angiographic end point appears to be a valid alternative to that at 90 minutes and may permit earlier decisions regarding post-thrombolytic intervention.

Coronary Angiography↗
PubMed2001

Impact of contrast agent type (ionic versus nonionic) used for coronary angiography on angiographic, electrocardiographic, and clinical outcomes following thrombolytic administration in acute myocardial infarction.

The goal of this study was to examine the relationship between contrast agent type (ionic vs. nonionic) and angiographic, electrocardiographic, and clinical outcomes after thrombolytic administration. Ionic or nonionic contrast agents were selected in a nonrandomized fashion for 90-min angiography and percutaneous coronary intervention (PCI) following thrombolytic administration in the TIMI 14 trial [tissue plasminogen activator (tPA) or reteplase (rPA) vs. low-dose lytic + abciximab]. There was no relationship between contrast agent type and overall patency, rate of TIMI grade 3 flow, or corrected TIMI frame counts (CTFCs) in open culprit arteries and in post-PCI patency rates or post-PCI CTFCs. In patients treated with ionic contrast, ejection fractions at 90 min were slightly but significantly lower (56.2 +/- 16.5, n = 122, vs. 59.8 +/- 14.4, n = 322; P = 0.02), chest pain duration was longer (2.8 +/- 4.1 hr, n = 255, vs. 1.7 +/- 3.6, n = 550; P = 0.0003), and complete ST segment resolution was less frequent (41.5% vs. 50.8%; P = 0.04). While there was no difference in epicardial blood flow, ionic contrast agent use was associated with poorer ST segment resolution, longer chest pain duration, and poorer ejection fractions, perhaps as a result of microvascular dysfunction.

Aged↗
PubMed2001

Issues in the assessment of the safety and efficacy of tenecteplase (TNK-tPA).

While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety of alteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 lb) without an increased risk of ICH or death. Furthermore, the results of TNK-tPA clinical trials showed that even at the highest weight-optimized dosage of 50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. In elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.

Body Weight↗
PubMed2001

Use of risk stratification to identify patients with unstable angina likeliest to benefit from an invasive versus conservative management strategy.

OBJECTIVES: This study was designed to determine whether patient characteristics collected at presentation can identify which patients benefit from immediate coronary angiography and revascularization. BACKGROUND: Risk stratification may offer a method for identifying which patients with unstable angina or non-Q-wave myocardial infarction (NQMI) are likeliest to benefit from invasive management strategies. METHODS: The analysis was based on data from a randomized controlled trial that enrolled 1,473 patients presenting with unstable angina or NQMI who were randomly assigned to an early invasive or early conservative (medical) management strategy. We constructed a risk-stratification score for each patient based on adjusted odds ratios for clinical variables likely to predict adverse outcomes. We stratified all trial subjects by their risk scores and studied the rates of death or myocardial infarction (MI) of the early invasive management strategy in each stratum. RESULTS: The final multivariate model included older age, ST segment depression on presentation, history of complicated angina before presentation, and elevation in baseline creatine kinase-MB fraction. Although patients with a higher risk score had an increased rate of death or MI within 42 days and 365 days (p < 0.001) in both management strategies, early invasive management for patients in the high and very high risk categories was associated with a lower rate of death or MI within 42 days compared with conservative management. No such benefit was seen in patients in the larger group of patients in the very low, low or moderate risk categories (p = 0.03 for the interaction between risk category and management assignment). CONCLUSIONS: Risk stratification may be an effective method for identifying those patients with unstable angina or NQMI most likely to benefit from early invasive management. Selective use of early invasive management can have a substantial impact in reducing morbidity and mortality in higher risk patients, but may not be warranted in lower risk patients.

Aged↗
PubMed2001

Determination of a weight-adjusted dose of TNK-tissue plasminogen activator.

BACKGROUND: TNK-tissue plasminogen activator (TNK-tPA) is a potent new thrombolytic agent for treatment of acute myocardial infarction. TNK-tPA was evaluated in 4214 patients in two dose-ranging trials (Thrombolysis in Myocardial Infarction [TIMI] 10B and Assessment of the Safety and Efficacy of a New Thrombolytic Agent [ASSENT] I). This article describes the rationale for the weight-adjusted dosing regimen of TNK-tPA that was selected for evaluation in the large phase III clinical trial ASSENT II. METHODS: Weight-based analyses were conducted with data from both the angiographic TIMI 10B trial, which compared TNK-tPA in doses of 30 mg, 40 mg, and 50 mg with the accelerated regimen of tPA in 889 patients, and the ASSENT I trial, which evaluated the safety of TNK-tPA in doses of 30 mg, 40 mg, and 50 mg in 3301 patients. Graphic and statistical analytic methods were used to assess relationships between weight and efficacy or safety measurements. RESULTS: The plasma clearance, initial plasma concentrations, and plasma steady-state volume of distribution all increased with decreasing body weight (all P<.001). The corrected TIMI frame count decreased (flow was faster) (P =.001) and the TIMI grade 3 flow increased with an increasing weight-standardized dose of TNK-tPA (P<.008). Mortality was inversely related to dose, but this relationship was not statistically significant. There was no clear relationship between intracranial hemorrhage and dose and weight. Serious bleeding events increased with increasing weight-standardized dose (P<.02). CONCLUSIONS: On the basis of these analyses, a weight-adjusted dosing regimen was devised for TNK-tPA that included five dosing increments and was based on a target weight-standardized dose of 0.53 mg/kg.

Aged↗
PubMed2001

Abciximab and early adjunctive percutaneous coronary intervention are associated with improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. METHODS: ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. RESULTS: Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution (P =.008). CONCLUSIONS: A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy.

Abciximab↗
PubMed2001

Myoglobin levels at 12 hours identify patients at low risk for 30-day mortality after thrombolysis in acute myocardial infarction: a Thrombolysis in Myocardial Infarction 10B substudy.

OBJECTIVE: We sought to identify, by use of serum cardiac markers, patients at low risk for 30-day mortality after ST-segment elevation myocardial infarction. BACKGROUND: Baseline cardiac markers are currently used to identify patients at increased risk for short-term events. We hypothesized that serum markers measured after treatment could identify patients at low risk for 30-day mortality. METHODS: A total of 839 patients from the Thrombolysis in Myocardial Infarction (TIMI) 10B study had myoglobin, cardiac-specific troponin-I, creatine kinase (CK)-MB measurements at the following time points; baseline, 90 minutes, and 3 and 12 hours after thrombolysis. By use of receiver operating characteristic analysis, thresholds were derived to predict 30-day mortality with at least 95% negative predictive value. RESULTS: Ninety minutes after thrombolysis myoglobin was superior to troponin-I or CK-MB in identifying patients at low risk for mortality. The 30-day mortality for 12-hour myoglobin < or = 239 ng/mL was 1.4% compared with 9.1% for levels > 239 ng/mL (P < .001). For 12-hour troponin-I (threshold 81.5 ng/mL), mortality was 1.9% versus 6.6% (P = .001) if above threshold; similarly for CK-MB at 12 hours (threshold 191 ng/mL) it was 3.3% versus 7.9% (P = .02). Multivariate analysis of baseline and posttreatment cardiac markers, age, sex, infarct artery location, and 90-minute TIMI flow grade identified only 12-hour myoglobin among the cardiac markers as independently predicting a low 30-day mortality (odds ratio 0.11, 95% confidence interval 0.02-0.50, P < .004). CONCLUSION: Serum cardiac markers can identify greater than two thirds of patients at low risk for 30-day mortality. A low 12-hour myoglobin level (< or = 239 ng/mL in this substudy) identifies such patients at low risk and could potentially assist in early risk stratification and triage after ST-segment elevation myocardial infarction.

Aged↗