Taxus Liberté Post Approval Study: Dual Antiplatelet Therapy - TL-PAS: DAPT

Description:

This is a substudy of the DAPT trial of patients who received a Taxus Liberté stent.

Hypothesis:

A 30-month duration of DAPT with aspirin and prasugrel would be superior to a 12-month duration in patients undergoing percutaneous coronary intervention (PCI) with a Taxus Liberté stent.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patient Populations:

  • Age >18 years
  • PCI with stent deployment within the past 24 hours
  • No known contraindication to DAPT for at least 30 months after enrollment and stent implantation
  • At 12 months, patient free from death, MI, stroke, repeat coronary revascularization, major bleeding, and stent thrombosis, and compliant with DAPT following stent implantation

    Number of screened applicants: 4,199
    Number of enrollees: 2,191
    Duration of follow-up: 30 months following initial screening
    Mean patient age: 59.4 years
    Percentage female: 25%

Exclusions:

At initial screening:

  • Index procedure stent placement with stent diameter <2.25 mm or >4.0 mm
  • Pregnant women
  • Planned surgery necessitating discontinuation of DAPT within the 30 months following enrollment
  • Current medical condition with a life expectancy of <3 years
  • Subjects on warfarin or similar anticoagulant therapy 
  • Subjects with hypersensitivity or allergies to one of the drugs or components
  • Subjects treated with both drug-eluting stents and bare-metal stents during the index procedure

At 12 months:

  • Pregnant women
  • Subject switched thienopyridine type or dose within 6 months prior to randomization
  • PCI or cardiac surgery between 6 weeks post-index procedure and randomization
  • Planned surgery necessitating discontinuation of antiplatelet therapy within 21 months
  • Current medical condition with a life expectancy of <3 years
  • Subjects on warfarin or similar anticoagulant therapy

Primary Endpoints:

  • MACCE at 18 months following enrollment (30 months from index procedure)
  • Stent thrombosis at 18 months (30 months from index procedure)
  • Moderate or severe GUSTO bleeding at 18 months (30 months from index procedure)

Secondary Endpoints:

  • All-cause mortality

Drug/Procedures Used:

Patients were enrolled 72 hours after stent placement and were given open-label aspirin and prasugrel for 12 months. At 12 months, patients without an ischemic or bleeding complication and with documented compliance, were randomized in a 1:1 fashion to receive an additional 18 months of DAPT or matching placebo.

Principal Findings:

A total of 2,191 patients were randomized: 1,098 to prolonged DAPT and 1,093 to placebo. Baseline characteristics were fairly similar between the two arms. Approximately 33% had diabetes mellitus and 30% were smokers. Indication for PCI was stable angina in 30%, ST-elevation myocardial infarction (STEMI) in 10% and NSTE-acute coronary syndrome (NSTE-ACS) in 50%. The mean number of lesions treated was 1.35, with about 1.45 stents/patient. Reference vessel diameter was 3.0 mm.

The primary endpoint of major adverse cardiac and cerebrovascular events (MACCE) at 540 days (30 months) was significantly lower in the continued DAPT arm compared with placebo (3.7% vs. 8.8%, hazard ratio 0.41, 95% CI 0.28-0.59, p < 0.001). There were reductions in all MI (1.9% vs. 7.1%, p < 0.001) and stent thrombosis (0.2% vs. 2.9%, p < 0.001). No differences were noted in all-cause mortality (2.0% vs. 1.9%, p = 0.85). GUSTO moderate and severe bleeding were numerically higher with prolonged DAPT (2.4% vs. 1.7%, p = 0.23).

Interpretation:

The results of the TL-PAS: DAPT trial indicate that prolonged duration of DAPT with aspirin and prasugrel for 30 months following index PCI with the Taxus Liberté stent results in lower stent thrombosis and recurrent MIs compared with a 12-month duration of DAPT, with similar rates of bleeding and all-cause mortality. This is not a separate clinical trial, but a subset of the DAPT trial.

Of all the DES used in the DAPT trial, the magnitude of benefit appears to be highest in the patients with paclitaxel-eluting stents (PES). One reason for this is that the elution kinetics for PES are very different from the other drugs. Some studies indicate that the paclitaxel coating on the stent never completely goes away; thus, there is constant paclitaxel elution for very prolonged durations, perhaps even life-long. This design makes stent thrombosis a more likely event with PES than with other DES after withdrawal of DAPT and is supported by the fact that in the control arm of this substudy; the stent thrombosis rate is twofold that observed in the control arm of the DAPT trial. Prasugrel might be a more potent inhibitor of stent thrombosis events in patients receiving PES than clopidogrel, although this trial was not designed to compare prasugrel to clopidogrel. Moreover, prasugrel is currently not indicated in the treatment of patients without ACS.

References:

Garratt KN, Weaver WD, Jenkins RD, et al. Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after Taxus Liberté paclitaxel-eluting coronary stent placement. Circulation 2014;Nov 16:[Epub ahead of print].

Presented by Dr. Kirk N. Garratt at the American Heart Association Scientific Sessions, Chicago, IL, November 16, 2014.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Interventions and ACS, Chronic Angina

Keywords: Paclitaxel, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Follow-Up Studies, Angina, Stable, Thrombosis, Thiophenes, Piperazines, Aspirin, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention, AHA Annual Scientific Sessions


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