Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial

JACC Cardiovasc Interv. 2013 Aug;6(8):777-89. doi: 10.1016/j.jcin.2013.04.011.

Abstract

Objectives: This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial.

Background: The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES.

Methods: The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat.

Results: At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005).

Conclusions: The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220).

Keywords: ACS; ARC; Academic Research Consortium; BES; BMS; CI; DES; KM; Kaplan-Meier; MACE; MI; PCI; POCE; RR; SES; ST; ST-segment elevation myocardial infarction; STEMI; TVR; acute coronary syndrome; bare-metal stent(s); biodegradable polymer; biolimus-eluting stent(s); confidence interval; drug-eluting stent(s); drug-eluting stents; durable polymer; major adverse cardiac events; myocardial infarction; patient-oriented composite endpoint; percutaneous coronary intervention; rate ratio(s); sirolimus-eluting stent(s); stent thrombosis; target vessel revascularization.

Publication types

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

MeSH terms

  • Absorbable Implants*
  • Aged
  • Cardiovascular Agents / administration & dosage*
  • Chi-Square Distribution
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Coronary Thrombosis / diagnosis
  • Coronary Thrombosis / etiology
  • Coronary Thrombosis / mortality
  • Coronary Thrombosis / prevention & control*
  • Drug-Eluting Stents*
  • Europe
  • Female
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control
  • Odds Ratio
  • Percutaneous Coronary Intervention / adverse effects
  • Percutaneous Coronary Intervention / instrumentation*
  • Percutaneous Coronary Intervention / mortality
  • Polymers*
  • Proportional Hazards Models
  • Prospective Studies
  • Prosthesis Design
  • Risk Factors
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Time Factors
  • Treatment Outcome

Substances

  • Cardiovascular Agents
  • Polymers
  • umirolimus
  • Sirolimus

Associated data

  • ClinicalTrials.gov/NCT00389220