Comparison of Drug Eluting and Bare Metal Stents With or Without Abciximab in ST Elevation Myocardial Infarction - DEBATER

Mar 19, 2012
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Unrestricted research grants from Johnson & Johnson (Cordis), Guidant, Abbott, and the Friends of the Heart Foundation (“Stichting Vrienden van het Hart”) in Eindhoven, the Netherlands.
Date Presented:
01/01/2009
Date Published:
01/01/2012
Date Updated:
03/19/2012
Original Posted Date:
03/19/2012
References

Description:

DEBATER is a 2 x 2 trial, in which patients presenting with ST-elevation myocardial infarction (STEMI) were randomized to either sirolimus-eluting stents (SES) or bare-metal stents (BMS), and abciximab or no abciximab.

Hypothesis:

SES would be superior to BMS, and abciximab would be superior to no abciximab in patients undergoing percutaneous coronary intervention (PCI) for STEMI.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patients Screened: 2,977
Patients Enrolled: 907
Mean Follow Up: 1 year
Mean Patient Age: 60 years
Female: 24%

Patient Populations:

  • Patient presenting with STEMI
  • Age ≥18 years

Exclusions:

  • Oral anticoagulation
  • Contraindications for abciximab, clopidogrel, or stenting
  • Therapy with other glycoprotein IIb/IIIa inhibitors within 24 hours
  • Thrombolytic therapy within 24 hours
  • No informed consent
  • Cardiogenic shock
  • Poor short-term prognosis due to comorbidities

Primary Endpoints:

  • SES vs. BMS: Death, MI, stroke, repeat revascularization, bleeding at 1 year
  • Abciximab vs. no abciximab: Death, target-vessel MI, TVR, bleeding within 30 days

Drug/Procedures Used:

SES (Cypher®) or BMS (at the discretion of the interventionalist). Abciximab was given as a 0.25 mg/kg infusion during PCI, followed by 0.125 µg/kg/min for 12 hours following PCI.

Concomitant Medications:

Aspirin (300 mg chewed or 500 mg intravenous), clopidogrel (600 mg), and unfractionated heparin (5000 U bolus) in the ambulance; all patients received an additional 5000 U UFH prior to PCI. After primary PCI, all patients received aspirin 80 mg/day indefinitely and clopidogrel 75 mg/day for 1 month (BMS) or 6-12 months (SES). Beta-blockers (90%), statins (60%).

Principal Findings:

A total of 907 patients were enrolled, 441 to SES and 466 to BMS, and 457 to abciximab and 450 to no abciximab. Baseline characteristics were fairly similar between the two groups. About 10% of the patients were diabetic, 29% had hypertension, and 28% had hyperlipidemia. The median time to reperfusion after arrival in the cath lab was 15 minutes, and the median time from onset of symptoms to reperfusion was 163 minutes. The infarct-related artery was the right coronary artery in 47% of the patients, and about 25% of the patients had TIMI (Thrombolysis in Myocardial Infarction) 2-3 flow even before PCI.

SES vs. BMS: There was a significant reduction in the primary composite endpoint of death, MI, stroke, repeat revascularization, and bleeding at 1 year in the SES arm, as compared with the BMS arm (16.5% vs. 25.8%, relative risk [RR] 0.64, 95% confidence interval [CI] 0.49-0.84, p = 0.001). This was driven primarily by a reduction in target lesion revascularization (TLR) (9.8% vs. 16.8%, p = 0.003). No difference was noted in the incidence of death (2.6% vs. 2.2%, p = 0.74) and definite or probable stent thrombosis (4% in both arms, p = 0.98).

Abciximab vs. no abciximab: There was a significant reduction in the primary composite endpoint of death, target vessel MI, target vessel revascularization (TVR), or bleeding at 30 days (8.2% vs. 12.4%%, RR 0.65, 95% CI 0.43-0.99, p = 0.04). This was driven primarily by a significant reduction in TVR (6.6% vs. 11.1%, p = 0.02). Stent thrombosis at 30 days was also lower in the abciximab arm (1.0% vs. 6.7%, p < 0.001), although there was no difference in the incidence of death/MI at 1 year (5.5% vs. 5.5%, p = 0.97). ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) bleeding was significantly increased in the abciximab arm at 30 days (5.7% vs. 2.8%, p = 0.03).

Interpretation:

The results of this trial indicate that SES result in significant reductions in target vessel failure (TVF) and major adverse cardiac events (MACE) at 1 year, as compared with BMS in patients presenting with STEMI. This has been noted in multiple trials before, such as HORIZONS-AMI Stent, SESAMI, and TYPHOON. The event rates were higher in the SES arm in this trial though, and it is unknown if this represents a different, and possibly sicker, subset of patients with STEMI.

Also, while abciximab is associated with a reduction in TVF at 30 days compared with no abciximab, MACE rates at 1 year were similar, mainly due to an increased risk of bleeding with abciximab. This is similar to earlier studies as well, in which the beneficial effect of glycoprotein IIb/IIIa inhibitors in reducing ischemic complications is tempered by an increase in the risk of bleeding. The HORIZONS-AMI trial indicates that bivalirudin may be a safer alternative to abciximab in STEMI patients, since a similar reduction in ischemic complications is noted, without an increase in the risk of bleeding.

References:

Wijnbergen I, Helmes H, Tijssen J, et al. A comparison of drug-eluting and bare-metal stents for primary percutaneous coronary intervention with or without abciximab in ST-segment elevation myocardial infarction: the Eindhoven Reperfusion Study (DEBATER). JACC Cardiovasc Interv 2012;5:313-322.

Presented by Dr. Rolf Michels at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2009), San Francisco, September 25, 2009.

Keywords: Risk, Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Hyperlipidemias, Sirolimus, Immunoglobulin Fab Fragments, Hirudins, Stents, Percutaneous Coronary Intervention, Metals, Thrombosis, Catheterization, Peptide Fragments, Confidence Intervals, Hypertension, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex


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