Drug Elution and Distal Protection in Acute Myocardial Infarction - DEDICATION: Stent Study

Sep 20, 2008
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Summary Supplemental Reviewer:
Trial Sponsor:
Supported by unrestricted grants from Cordis/Johnson & Johnson, Medtronic, Abbott, and Boston Scientific.
Date Presented:
01/01/2007
Date Published:
01/01/2008
Date Updated:
09/20/2008
Original Posted Date:
09/20/2008
References

Description:

The goal of the trial was to evaluate use of a drug-eluting stent (DES) compared with a bare-metal stent (BMS) among patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).

Hypothesis:

DES will be superior to BMS for AMI.

Study Design

  • Randomized
  • Parallel

Patients Screened: 1,687
Patients Enrolled: 626
Mean Follow Up: 8 months, 3 years
Mean Patient Age: 62 years
Female: 27%
Mean Ejection Fraction: 48%

Patient Populations:

  • Acute onset typical chest pain within 12 hours
  • ST-elevation of >4 mm in contiguous leads
  • High-grade stenosis or occlusion of a native major coronary artery that can be crossed with a soft or intermediate tip guidewire
  • Possibility to perform distal protection of the infarct-related artery

Exclusions:

  • History of previous MI
  • Use of fibrinolytic agents for the index infarction
  • Left main stenosis
  • Heavy calcification of abdominal aorta or occlusive iliofemoral disease hampering access to the coronary ostias by the femoral route
  • Known renal failure
  • Other significant cardiac disease
  • Other severe disease with an expected survival <1 year
  • Known allergy to clopidogrel or contrast media
  • Gastrointestinal bleeding within 1 month

Primary Endpoints:

Late lumen loss at 8 months

Secondary Endpoints:

Cardiac events at 8 months

Drug/Procedures Used:

Patients undergoing primary PCI were randomized to the use of a DES (n = 313) or BMS (n = 313). Choice of DES was at the discretion of the investigator. Angiographic follow-up was performed at 8 months. Patients also received distal embolic protection vs. PCI without embolic protection by 2 x 2 factorial design (results presented separately).

Concomitant Medications:

Patients received 300-500 mg aspirin, 300-600 mg clopidogrel, and 10,000 U unfractionated heparin. A beta-blocker was administered if blood pressure and heart rate allowed. Patients were treated with a glycoprotein (GP) IIb/IIIa inhibitor in the catheterization laboratory.

Principal Findings:

The infarct artery was the left anterior descending in 42% of patients, and 63% had single-vessel disease. GP IIb/IIIa inhibitors were used in 96% of cases. In the DES arm, the sirolimus-eluting stent was used in 47% of cases and the paclitaxel-eluting stent in 40%. Final Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow was present in 90% of patients at the end of the PCI.

At 8-month angiographic follow-up, in-stent late lumen loss was smaller in the DES group compared with the BMS group (0.09 mm vs. 0.69 mm, p < 0.001). Percent diameter stenosis was lower in the DES group (21.7% vs. 34.0%, p < 0.001), as was binary restenosis (4.8% vs. 16.6%, p < 0.001). Major adverse cardiac events (MACE) at 8 months were lower in the DES group compared with the BMS group (8.9% vs. 14.4%, p < 0.05), driven by a reduction in target lesion revascularization (TLR) (5.1% vs. 13.1%, p < 0.001). There was no difference in MI (1.6% vs. 2.6%, p = 0.42). Cardiac death trended higher in the DES group (4.2% vs. 1.6%, p = 0.09), as did overall mortality (5.1% vs. 2.6%, p = 0.14). There was no difference in stent thrombosis, with seven cases in the DES group versus eight cases in the BMS group (p = 0.72).

At 3 years, the incidence of MACE was significantly lower in the DES arm, as compared with the BMS arm (11.5% vs. 18.2%, p = 0.024). This was driven predominately by a reduction in the need for TLR (6.1% vs. 16.3%, p < 0.001). There was no difference in MI between the two arms (1.9% vs. 3.2%, p = 0.45). The trend towards an increase in all-cause mortality with DES noted at 8 months was still present at 3 years (10.5% vs. 6.4%, p = 0.08). However, there was a significant increase in cardiovascular mortality with DES at the end of 3 years (6.1% vs. 1.9%, p = 0.013). However, the incidence of stent thrombosis was similar between the two arms (p = 0.5).

Interpretation:

Among patients undergoing primary PCI for AMI, use of a DES was associated with a reduction in late lumen loss at 8 months compared with use of a BMS, but cardiac mortality trended higher.

Previous trials of DES use for primary PCI have been small and shown mixed results, with some showing a reduction in composite events driven by TLR and others showing no difference in composite events. There was a trend toward an increase in cardiac death with DES in the present study, although the increase was not explained by a difference in the rate of stent thrombosis, which was identical in the two arms. The 3,600-patient HORIZONS-AMI trial will compare DES with BMS in patients undergoing primary PCI, and will be the largest study to date in this population. One-year results of the trial are scheduled to be released in late 2008.

References:

Kelbaek H, Thuesen L, Helqvist S, et al., on behalf of the DEDICATION Investigators. Drug-eluting versus bare metal stents in patients with ST-segment-elevation myocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION) trial. Circulation 2008;118:1155-62.

Presented by Dr. Henning Kelbaek, at TCT 2007, Washington, DC.

Keywords: Paclitaxel, Myocardial Infarction, Follow-Up Studies, Metals, Chest Pain, Thrombosis, Drug-Eluting Stents, Constriction, Pathologic, Sirolimus, Platelet Membrane Glycoprotein IIb, Stents, Percutaneous Coronary Intervention


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