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LEADERS FREE published: Drug-coated stent confers benefit at 2 years in patients at high bleeding risk
Confirming results previously presented, in patients at high risk for bleeding, a drug-coated stent appears to confer greater safety and efficacy benefits vs. a bare-metal stent at 2 years, according to recent findings from the LEADERS FREE trial.
In a prospective, multicenter, double blind trial, researchers assessed 2,466 patients at high bleeding risk from 68 sites of the trial. Eligible participants had a clinical indication for PCI and met at least one high bleeding risk criteria.
Patients were randomly allocated to undergo treatment with a polymer-free drug-coated stent (DCS; BioFreedom, Biosensors International) or a BMS (Gazelle, Biosensors International), followed by 1 month of dual antiplatelet therapy.
The primary safety endpoint was a composite of cardiac death, MI, or definite or probable stent thrombosis. Clinically driven target lesion revascularization was the primary efficacy endpoint. The following were prespecified secondary endpoints: all-cause and cardiac mortality, bleeding, MI, stent thrombosis and types of coronary revascularization.
The researchers found that, of 2,432 patients evaluated, 2,386 (98.1%) were followed until death or 730 days. At 730 days, single antiplatelet therapy was being administered to 78.8% of patients in the DCS group and 76.8% in the BMS group, whereas DAPT was given to 5.3% of patients in the DCS group and 7.6% in the BMS group. No antiplatelet drug was given to 15.8% of patients in the DCS group and 15.6% of patients in the BMS group, and oral anticoagulants were administered to 37.7% of patients in the DCS group and 38% of patients in the BMS group.
DCS safer, more effective
Between the 1- and 2-year follow-up, new occurrences of a primary safety endpoint occurred 53 times in 37 patients with a DCS and 44 times in 29 patients with a BMS. Those with a BMS had more frequent occurrences of the primary safety outcome at 2 years vs. the DCS group (15.3% vs. 12.6%; HR = 0.8; 95% CI, 0.64-0.99).
Between 1 and 2 years, 24 new TLRs occurred in 20 patients with DCS and 43 new TLRs occurred in 29 patients with BMS. Clinically driven TLR was necessary at least once in 6.8% of patients in the DCS group and 12% in the BMS group at 2-year follow-up (HR = 0.54; 95% CI, 0.41-0.72).
No significant differences were seen between the groups in terms of all-cause mortality (13.1% for DCS vs. 13.8% for BMS; HR = 0.94; 95% CI, 0.75-1.17) or cardiac mortality (6.6% vs. 6.9%; HR = 0.94; 95% CI, 0.69-1.28).
Between 1- and 2-year follow-up, there were 48 MIs (25 in 20 patients with a DCS and 23 in 14 patients with a BMS) and two very late definite or probable stent thromboses (one in each group). Between randomization and 2 years, there was a lower incidence of coronary thrombotic events in the DCS group vs. the BMS group (8.2% vs. 10.6%; P = .045). At 2 years, the rates of major bleeding were comparable in the DCS and BMS groups (8.9% vs. 9.2%; P = .95).
The researchers identified eight baseline and procedural characteristics that were associated with 2-year major bleeding, primary safety endpoint events or both. Those related to the primary safety endpoint only included congestive HF, multivessel disease, number of stents and stent type; those associated with bleeding events only included planned oral anticoagulation and increased plasma creatinine; and those related to both included age at least 75 years and low hemoglobin.
The risk for all-cause mortality 1 year after a major bleed was 27.1%, and the risk for all-cause mortality 1 year after a coronary thrombotic event was 26.3%. For both outcomes, mortality risk was highest within the first week after such events, especially in the case of coronary thrombotic events. This excess risk then diminished over time, according to the researchers.
Viable alternative
In a related editorial, C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, wrote that in patients at high risk for bleeding, DCS may offer a viable alternative to BMS.
“In managing the patient at high risk of bleeding, rather than going back to an older stent design and using a BMS as has been recommended by some, polymer-free metallic [DCS] such as that studied in the LEADERS FREE trial offer an alternative strategy,” Gibson wrote. “This [DCS] transfers the drug into the wall of the artery early and quickly over a month and speeds vessel healing as opposed to a traditional polymer-coated DES that transfers antirestenotic drugs over several months.” – by Jennifer Byrne
Disclosure: The study was funded by Biosensors Europe. Please see the full study for a list of the researchers’ relevant financial disclosures. Gibson reports receiving consultant fees and research support from Bayer, Janssen and Johnson & Johnson, and research support from Portola.