Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk

N Engl J Med. 2015 Nov 19;373(21):2038-47. doi: 10.1056/NEJMoa1503943. Epub 2015 Oct 14.


Background: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month.

Methods: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization.

Results: We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the bare-metal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001).

Conclusions: Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Combined Modality Therapy
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / therapy*
  • Double-Blind Method
  • Drug-Eluting Stents* / adverse effects
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymers
  • Prosthesis Design
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Stents / adverse effects


  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Polymers
  • umirolimus
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT01623180