Trial to Assess the Use of the Cypher Sirolimus-Eluting Stent in Acute Myocardial Infarction Treated With Balloon Angioplasty - TYPHOON: 1- and 4-Year Follow-Up

Description:

The goal of the trial was to evaluate treatment with sirolimus-eluting stents compared with bare-metal stents among patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI).

Hypothesis:

Sirolimus-eluting stents would be superior at reducing the need for revascularization.

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 712
Mean Follow Up: 4 years
Mean Patient Age: 59 years
Female: 22%

Patient Populations:

Acute MI (defined as prolonged chest pain with ST-segment elevation) <12 hours since onset and a culprit lesion in a native coronary artery suitable for stenting

Exclusions:

Prior MI, Killip class >2, bifurcation lesion with a diseased side branch requiring treatment, unprotected left main coronary disease with >50% stenosis, >50% stenosis proximal or distal to the artery requiring revascularization, or severe multivessel disease of the nonculprit artery requiring coronary artery bypass grafting

Primary Endpoints:

Target vessel failure at 1 year, defined as TVR, recurrent MI, or cardiac death

Secondary Endpoints:

  • Cardiac death
  • Recurrent MI
  • TLR
  • Stent thrombosis

Drug/Procedures Used:

Patients were randomized after the culprit lesion was visualized to primary PCI with either sirolimus-eluting stents (n = 355) or bare-metal stents (n = 357). Glycoprotein IIb/IIIa inhibitors were used at the discretion of the treating physician. Angiographic follow-up at 8 months was performed as a substudy in 184 patients.

Concomitant Medications:

Aspirin (≥100 mg) and clopidogrel (300 mg load and 75 mg/d for 6 months)

Principal Findings:

Infarct artery was the left anterior descending in 45% of patients. Glycoprotein IIb/IIIa inhibitors were used in 72% of patients. Median door-to-balloon time was 60 minutes. TIMI flow grade 3 was present at the end of the intervention in 96% of patients.

The primary endpoint of target vessel failure at 1 year occurred in 7.3% of the sirolimus-eluting stent group versus 14.3% of the bare-metal stent group (p = 0.004), driven by a reduction in target vessel revascularization (TVR) (5.6% vs. 13.4%, p < 0.001), with no difference in death (2.3% vs. 2.2%) or recurrent MI (1.1% vs. 1.4%, p > 0.99). Approximately 24% of participants underwent angiographic follow-up. Stent thrombosis did not differ between groups (3.4% with sirolimus-eluting stents vs. 3.6% with bare-metal stents, p > 0.99), but was relatively high overall.

Among the angiographic substudy cohort, in-stent late lumen loss was lower in the sirolimus-eluting stent group than the bare-metal stent group (0.14 mm vs. 0.83 mm, p < 0.0001).

At 4 years, 19% of the sirolimus-eluting stent group versus 16% of the bare-metal stent group remained on dual antiplatelet therapy. Target lesion revascularization (TLR) was 7.6% versus 14.9% (p = 0.002), cardiac death was 2.4% versus 4.1% (p = 0.37), recurrent MI was 5.2% versus 4.4% (p = 0.85), and cumulative stent thrombosis was 4.4% versus 4.8% (p = 0.83), respectively, for sirolimus versus bare-metal stents.

Interpretation:

Among patients with acute MI undergoing primary PCI, use of a sirolimus-eluting stent was associated with a reduction in the primary endpoint of target vessel failure at 1 year (and TLR at 4 years) compared with bare-metal stents. This was likely influenced by the quarter of participants that underwent study-mandated angiographic follow-up. Despite the low use of long-term dual antiplatelet therapy, individual outcomes, including cardiac death, MI, and stent thrombosis, appeared to be similar between the treatment arms at 4 years.

Several large randomized studies have been performed with drug-eluting stents in the setting of elective PCI, but little randomized data exist in the setting of ST-segment elevation MI (STEMI). The present trial is the first large-scale randomized study with sirolimus-eluting stents compared with bare-metal stents conducted exclusively in the STEMI population.

Another recent trial, the PASSION trial, did not demonstrate a reduction in TLR with paclitaxel-eluting stents over bare-metal stents in STEMI patients. However, there were several important differences between that trial in addition to the different drug-eluting stent used, including an absence of angiographic follow-up in the PASSION trial, which may have decreased the repeat revascularization rate, which was very low in both arms.

References:

Spaulding C, Teiger E, Commeau P, et al. Four-year follow-up of the trial to assess the use of the Cypher sirolimus-eluting coronary stent in acute myocardial infarction treated with balloon angioplasty (TYPHOON). JACC Cardiovasc Interv 2011;4:14-23.

Spaulding C, Henry P, Teiger E, et al. Sirolimus-eluting versus uncoated stents in acute myocardial infarction. N Engl J Med 2006;355:1093-104.

Presented by Dr. Christian Spaulding at the March 2006 i2 Annual Scientific Session, Atlanta, GA.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Myocardial Infarction, Follow-Up Studies, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Coronary Disease, Ticlopidine, Sirolimus, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Paclitaxel, Thrombosis, Chest Pain, Coronary Vessels


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