Grupo de Analisis de la Cardiopatia Isquemica Aguda-3 - GRACIA-3

Sep 19, 2010
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
RECAVA from the Spanish Ministry of Science of Innovation
Date Published:
01/01/2010
Date Updated:
09/19/2010
Original Posted Date:
09/19/2010
References

Description:

Paclitaxel-eluting stents will be more effective in preventing restenosis, and tirofiban will be more effective in improving reperfusion.

Hypothesis:

Paclitaxel-eluting stents will be more effective in preventing restenosis, and tirofiban will be more effective in improving reperfusion.

Study Design

  • Randomized
  • Parallel
  • Factorial

Patient Populations:

  • STEMI patients >18 years of age with symptom onset <12 hours prior to randomization
  • Killip class <3

    Number of enrollees: 436
    Duration of follow-up: 12 months
    Age range: mean 61 years
    Percentage female: 20%

Exclusions:

  • Cardiogenic shock
  • Suspected mechanical complication of MI
  • Prior coronary artery bypass grafting
  • Pregnancy
  • Significant noncardiac disease/condition that could limit participation in the study
  • Active bleeding or surgery in the last 2 weeks that contraindicates the use of study medication
  • Hypersensitivity to study medication
  • Contraindication to fibrinolysis
  • Renal failure (creatine >2.5 mg/dl)
  • Liver disease
  • Thrombocytopenia
  • Participation in another trial
  • Multivessel coronary disease not suitable for revascularization
  • Peripheral arterial disease

Primary Endpoints:

  • In-segment restenosis at 12 months
  • Epicardial and myocardial flow before and after PCI assessed by the angiographic perfusion score

Secondary Endpoints:

  • Stent thrombosis
  • Major bleeding

Drug/Procedures Used:

Eligible STEMI patients in Spain initially treated with tenecteplase and enoxaparin were randomized by 2 x 2 factorial design to tirofiban (n = 214) versus no tirofiban (n = 219) and also a paclitaxel-eluting stent (n = 217) versus a bare-metal stent (n = 216).

Tirofiban was initiated at least 2 hours after fibrinolysis.

Concomitant Medications:

All patients received aspirin 150-325 mg prior to catheterization and clopidogrel 300 mg immediately after PCI, then 75 mg daily for 1 year.

At discharge, in the paclitaxel-eluting stent/tirofiban group, the use of aspirin was 98%, clopidogrel 92%, statin 81%, beta-blocker 86%, and angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker 74%.

Principal Findings:

Overall, 433 patients were randomized, of which 34% presented to a hospital without PCI capabilities. During transfer to a PCI hospital, 7.5% suffered a cardiac complication (all successfully resolved). The median transportation distance was 45 km, which required a median transportation time of 61 minutes.

In the paclitaxel-eluting stent/tirofiban group, the mean age was 61 years, 20% were women, 19% had diabetes, systolic blood pressure was 134 mm Hg, median time from symptoms to fibrinolysis was 3.0 hours, and median time from fibrinolysis to angiography was 5.1 hours.

The incidence of in-segment restenosis at 12 months was 10.1% with the paclitaxel-eluting stent versus 11.3% with the bare-metal stent (p = 0.89). Late-lumen loss was 0.04 mm versus 0.27 mm (p = 0.003), respectively. Death, MI, revascularization, or stent thrombosis was 21% versus 15% (p = 0.14), and major bleeding was 3.7% versus 5.9% (p = 0.63), respectively.

Full reperfusion (angiographic perfusion score 10-12) was achieved in 65% of the tirofiban group versus 60% of the no tirofiban group (p = NS). Death, MI, revascularization, or stent thrombosis was 21% versus 16% (p = 0.17), and major bleeding was 6.1% versus 2.7% (p = 0.15), respectively.

Interpretation:

Among STEMI patients initially treated with fibrinolysis and LMWH, PCI with the use of paclitaxel-eluting stents and tirofiban was not superior to bare-metal stents without tirofiban. Considering randomization to stent type, paclitaxel-eluting stents did not reduce the primary outcome of in-segment restenosis at 12 months; however, there was less late lumen loss with numerically increased ischemic events. Considering randomization to glycoprotein IIb/IIIa inhibitor, full reperfusion was similar between the groups; however, major bleeding was numerically increased with tirofiban.

Prior studies have shown that after fibrinolysis, transfer for PCI appears beneficial compared with conservative management followed by rescue PCI. In the CARESS-IN-AMI trial, adjuvant therapy consisted of half-dose reteplase and abciximab, whereas in the TRANSFER-AMI trial, full-dose tenecteplase and glycoprotein IIb/IIIa inhibitors were used during PCI.

References:

Sanchez PL, Gimeno F, Ancillo P, et al. Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial. Circ Cardiovasc Interv 2010;3:297-307.

Keywords: Platelet Aggregation Inhibitors, Coronary Restenosis, Blood Pressure, Immunoglobulin Fab Fragments, Tyrosine, Stents, Paclitaxel, Metals, Thrombosis, Enoxaparin, Fibrinolysis, Spain, Tissue Plasminogen Activator, Diabetes Mellitus


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