SAN FRANCISCO –Polymer-free drug-coated stents (DCS) demonstrated superiority with respect to primary safety and efficacy end points compared with bare-metal stents (BMS) in patients with high bleeding risk.

Investigators in the ongoing randomized, double-blind LEADERS FREE trial studied patients typically excluded from trials involving stents and adjunctive therapy because of high bleeding risk, specifically as a result of prolonged use of dual antiplatelet therapy (DAPT).

Current guidelines support use of either a second-generation drug-eluting stent with a shortened course of DAPT or a BMS followed by 1 month of DAPT. However, the use of a BMS is associated with a higher risk of restenosis and reintervention than a drug-eluting stent.


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The researchers specifically examined the BioFreedom DCS (Biosensors Europe, Morges, Switzerland), which uses stent surface modification instead of a polymer to elute the lipophilic drug Biolimus. They enrolled a total of 2446 patients (1239 in the polymer-free DCS arm and 1227 in the BMS arm) with coronary artery disease and a clinical indication for percutaneous coronary intervention (PCI).

The primary safety end point was a composite of cardiac death, myocardial infarction (MI), or stent thrombosis, and the primary efficacy end point was clinically driven target-lesion revascularization (TLR). In the BMS group, 12.9% of patients experienced the primary safety end point, which was higher than the researchers’ prediction of 8%, vs 9.4% in the DCS group (estimated absolute risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; P<.001 for noninferiority). Meanwhile, TLR occurred in 5.1% of the DCS group and in 9.8% of the BMS group (-4.8 percentage points; 95% CI, -6.9 to -2.6; HR, 0.50; 95% CI, 0.37 to 0.69; P<.001). The difference in the rate of MI was also significant at 6.1% vs 8.9% in the DCS and BMS groups, respectively (HR, 0.68, 0.50-0.91; P=.01).

In addition to being reported at the Transcatheter Cardiovascular Therapeutics (TCT) 2015 meeting, the LEADERS FREE investigators simultaneously published their findings in the New England Journal of Medicine.

During a TCT press conference, Philip M. Urban, MD, Director of Invasive Cardiology at Hôpital de la Tour in Geneva, Switzerland, noted that the biggest advantages of having a polymer-free stent is that there are no polymer-related adverse effects and it enables the drug to “transfer rapidly into the vessel wall … approximately 98% within 30 days.”

While the exact percentage of patients who are at high risk for bleeding is unknown, Dr Urban estimates that the population ranges between “15% and 20%,” and “as baby boomers reach elderly age, this percentage will grow.” Study discussant Marco Valgimigli, MD, PhD, Professor of Cardiology at Inselspital, Bern, Switzerland, concurred, noting the population may be even larger, as registries in Bern place figures closer to 40%, indicating this will become a more important group with time.

“As expected in this high-risk population, despite the short course of DAPT, the rate of bleeding was high (7.2% of patients meeting criteria for the Bleeding Academic Research Consortium types 3 to 5 bleeding),” the researchers wrote. “In contrast, the rate of major bleeding ranged from 0.6% to 2.8% during the first year after PCI in trials that included patients at low to moderate risk who received DAPT for longer durations.”

Dr Urban explained that approximately one-third of the patients were on triple therapy, which was continued during the trial, so the high bleeding risk was unsurprising. “This is not the ideal duration for DAPT therapy,” he said. “It’s a trade-off.”

Disclosures: The trial was sponsored by Biosensors Europe (Morges, Switzerland).

References

  1. Urban P, Meredith IT, Abizaid A, et al. Polymer-free drug-coated coronary stents in patients at high bleeding risk. New Engl J Med. 2015. doi:10.1056/NEJMoa1503943.
  2. Urban P. How does the LEADERS FREE RCT impact current PCI and DAPT strategies?  Presented at: 27th Annual Transcatheter Cardiovascular Therapeutics Scientific Symposium; October 10-15, 2015; San Francisco, CA.