ContextThe benefits of abciximab in patients with ST-segment elevation myocardial
infarction (STEMI) are still a matter of debate.ObjectiveTo combine data from all randomized trials conducted with abciximab
in STEMI.Data SourcesFormal searches of electronic databases (MEDLINE, PubMed) from from
January 1990 to December 2004.Study SelectionWe examined all completed, published, randomized trials of abciximab
in STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, facilitated angioplasty, stenting, fibrinolysis, IIb-IIIa inhibitors,
and abciximab.Data ExtractionInformation on study design, type and dosage of drugs, inclusion and
exclusion criteria, number of patients, and clinical outcome was extracted
by 2 investigators. Disagreements were resolved by consensus.Data SynthesisEleven trials were analyzed, involving 27115 patients (12 602 [46.5%]
in the abciximab group, 14 513 [53.5%] in the control group). When compared
with the control group, abciximab was associated with a significant reduction
in short-term (30 days) mortality (2.4% vs 3.4%, P = .047)
and long-term (6-12 months) mortality (4.4% vs 6.2%, P = .01)
in patients undergoing primary angioplasty but not in those treated with fibrinolysis
or in all trials combined. Abciximab was associated with a significant reduction
in 30-day reinfarction, both in all trials combined (2.1% vs 3.3%, P<.001), in primary angioplasty (1.0% vs 1.9%, P = .03), and in fibrinolysis trials (2.3% vs 3.6%, P<.001). Abciximab did not result in an increased risk
of intracranial bleeding (0.61% vs 0.62%, P = .62)
but was associated with an increased risk of major bleeding complications
when combined with fibrinolysis (5.2% vs 3.1%, P<.001)
but not with primary angioplasty (4.7% vs 4.1%, P = .36).ConclusionsThis meta-analysis shows that, when compared with the control group,
adjunctive abciximab for STEMI is associated with a significant reduction
in 30-day and long-term mortality in patients treated with primary angioplasty
but not in those receiving fibrinolysis. The 30-day reinfarction rate is significantly
reduced in patients treated with either fibrinolysis or primary angioplasty.
A higher risk of major bleeding complications is observed with abciximab in
association with fibrinolysis.

http://www.columbiamedicine.org/education/r/Cardiology/ACS/IIB-IIIA%20inhibitors/JAMA%20Meta-Analysis.pdf

Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

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 th...

Combination Therapy With Abciximab Reduces Angiographically Evident Thrombus in Acute Myocardial Infarction A TIMI 14 Substudy

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(08)60268-8.pdf

Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial.

Background— Mechanically overloaded cardiomyocytes secrete a soluble interleukin-1 receptor family member called ST2. Serum levels of ST2 are associated with prognosis in nonischemic heart failure, but the predictive value of ST2 in patients with acute myocardial infarction is unknown. Methods and Results— ST2 levels were measured in serum from 810 patients with acute myocardial infarction in the Thrombolysis In Myocardial Infarction (TIMI) 14 (362 patients) and Enoxaparin and TNK-tPA With or Without GPIIb/IIIa Inhibitor as Reperfusion Strategy in STEMI (ENTIRE)-TIMI 23 (448 patients) clinical trials. Baseline levels of ST2 were significantly higher in those patients who died (0.379 versus 0.233 ng/mL, P=0.0001) or developed new congestive heart failure (0.287 versus 0.233 ng/mL, P=0.009) by 30 days. In an analysis of outcomes at 30 days by ST2 quartiles, both death (P=0.001) and the combined death/heart failure end point (P=0.001) showed a significant graded association with levels of ST2; furthermore, i...

Serum Levels of the Interleukin-1 Receptor Family Member ST2 Predict Mortality and Clinical Outcome in Acute Myocardial Infarction

Fifteen years ago, a panel of experts representing the full spectrum of cardiovascular disease (CVD) research and practice assembled at a workshop to examine the state of knowledge about CVD. The leaders of the workshop generated a hypothesis that framed CVD as a chain of events, initiated by a myriad of related and unrelated risk factors and progressing through numerous physiological pathways and processes to the development of end-stage heart disease (Figure 1). 1 They further hypothesized that intervention anywhere along the chain of events leading to CVD could disrupt the pathophysiological process and confer cardioprotection. The workshop participants endorsed this paradigm but also identified the unresolved issues relating to the concept of a CVD continuum. There was limited availability of clinical trial data and pathobiological evidence at that time, and the experts recognized that critical studies at both the mechanistic level and the clinical level were needed to validate the concept of a chain of events leading to end-stage CVD. In the intervening 15 years, new evidence for underlying pathophysiological mechanisms, the development of novel therapeutic agents, and the release of additional landmark clinical trial data have confirmed the concept of a CVD continuum and reinforced the notion that intervention at any point along this chain can modify CVD progression. In addition, the accumulated evidence indicates that the events leading to disease progression overlap and intertwine and do not always occur as a sequence of discrete, tandem incidents. Furthermore, although the original concept focused on risk factors for coronary artery disease (CAD) and its sequelae, the CVD continuum has expanded to include other areas such as cerebrovascular disease, peripheral vascular disease, and renal disease. Since its conception 15 years ago, the CVD continuum has become much in need of an update. Accordingly, this 2-part article will present a critical and comprehensive update of the current evidence for a CVD continuum based on the results of pathophysiological studies and the outcome of a broad range of clinical trials that have been performed in the past 15 years. It is not the intent of the article to include a comprehensive listing of all trials performed as part of the CVD continuum; instead, we have sought to include only those trials that have had the greatest impact. Part I briefly reviews the current understanding of the pathophysiology of CVD and discusses clinical trial data from risk factors for disease through stable CAD. Part II continues the review of clinical trial data beginning with acute coronary syndromes and continuing through extension of the CVD continuum to stroke and renal disease. The article concludes with a discussion of areas in which future research might further clarify our understanding of the CVD continuum.

/pdf/the-cardiovascular-disease-continuum-validated-clinical-25rv06x45p.pdf

The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes Part I: Pathophysiology and Clinical Trial Evidence (Risk Factors Through Stable Coronary Artery Disease)

Aims Abciximab has previously been shown to enhance thrombolysis and improve myocardial perfusion when combined with reduced doses of alteplase. The purpose of the reteplase phase of TIMI 14 was to evaluate the effects of abciximab when used in combination with a reduced dose of reteplase for ST-elevation myocardial infarction. Methods and Results Patients (n=299) with ST-elevation myocardial infarction were treated with aspirin and randomized to a control arm with standard dose reteplase (10+10 U given 30 min apart) or abciximab (bolus of 0.25 mg. kg(-1)and 12-h infusion of 0.125 microg. kg(-1). min(-1)) in combination with reduced doses of reteplase (5+5 U or 10+5 U). Control patients received standard weight-adjusted heparin (bolus of 70 U. kg(-1); infusion of 15 U. kg(-1). h(-1)), while each of the combination arms with abciximab and reduced dose reteplase received either low dose heparin (bolus of 60 U. kg(-1); infusion of 7 U. kg(-1). h(-1)) or very low dose heparin (bolus of 30 U. kg(-1); infusion of 4 U. kg(-1). h(-1)). The rate of TIMI 3 flow at 90 min was 70% for patients treated with 10+10 U of reteplase alone (n=87), 73% for those treated with 5+5 U of reteplase with abciximab (n=88), and 77% for those treated with 10+5 U of reteplase with abciximab (n=75). Complete (>/=70%) ST resolution at 90 min was seen in 56% of patients receiving a reduced dose of reteplase in combination with abciximab compared with 48% of patients receiving reteplase alone. Conclusions Reduced doses of reteplase when administered in combination with abciximab were associated with higher TIMI 3 flow rates than reported previously for reduced doses of reteplase without abciximab and were at least as high as for full dose reteplase alone

/pdf/combination-reperfusion-therapy-with-abciximab-and-reduced-2pp2cufbsz.pdf

T.C Rehders

Papers

Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14