P2Y12i monotherapy following PCI reduces bleeding in patients at high bleeding risk
Ticagrelor monotherapy in patients at high bleeding risk undergoing percutaneous coronary intervention: TWILIGHT-HBR
Introduction and methods
Aim of the study
The TWILIGHT study previously showed that ticagrelor monotherapy after 3 month-treatment with ticagrelor plus aspirin following PCI, resulted in reduced bleeding risk at 12 months follow-up without ischemic harm compared to continued use of ticagrelor plus aspirin . This prespecified analysis of the TWILIGHT study investigated the treatment effects of ticagrelor monotherapy compared to ticagrelor plus aspirin in patients with high bleeding risk (HBR).
TWILIGHT enrolled patients undergoing successful PCI with a drug-eluting stent who met at least one clinical and one angiographic criterion associated with high risk of ischemic or bleeding events. Enrolled patients received ticagrelor (90 mg twice daily) plus aspirin (81-100 mg daily) for 3 months post-PCI. Patients who were adherent and event-free at 3 months were randomized in a 1:1 ratio to receive either placebo or aspirin in addition to open-label ticagrelor. The final study cohort included 6178 patients, of whom 1064 were considered as HBR (according to the definition of the ARC-HBR consensus statement).
The primary endpoint was BARC type 2, 3, or 5 bleeding up to 1 year after randomization. Another bleeding endpoint was the more severe BARC type 3 or 5 bleeding. Ischemic endpoints included the composite of all-cause death, MI or stroke and the composite of CV death, MI or ischemic stroke.
- Ticagrelor plus placebo reduced the risk of BARC type 2, 3, or 5 bleeding in HBR patients compared to ticagrelor plus aspirin (6.3% vs. 11.4%, HR 0.53, 95% CI 0.35-0.82, P=0.004) with an absolute risk difference (ARD) of -5.1% (95%CI -8.5% to -1.7%).These results were consistent in non-HBR patients (3.5% vs. 5.9%; ARD -2.3%, 95% CI -3.5% to -1.2%; HR 0.59, 95% CI 0.46–0.77, P<0.001, P for interaction =0.673).
- A significant reduction in the more severe BARC 3 or 5 bleeding was also observed in the ticagrelor plus placebo group compared to ticagrelor plus aspirin group in patients with HBR (1.6% vs 5.0%, HR 0.31, 95% CI 0.14–0.67, P= 0.003). The HR for BARC 3 or 5 bleeding with ticagrelor plus placebo vs ticagrelor plus aspirin in non-HBR patients was 0.62 (95% CI 0.36–1.09, P= 0.098; P for interaction=0.148). The ARD was significantly larger in HBR patients compared to non-HBR patients (difference in ARDs -3.0%, 95% CI -5.2% to -.08%, P=0.008).
- There was no significant difference between the two treatment arms for the composite ischemic endpoint of all-cause death, MI or stroke nor for the composite endpoint of CV death, MI or ischemic stroke in HBR patients (HR 1.16, 95% CI 0.71-1.90, P=0.554, and HR 1.09, 95%CI 0.66-1.82, P=0.736, respectively) and in non-HBR patients (HR=1.01, 95% CI 0.75-1.35, P=0.949, and HR 1.00, 95% CI 0.74-1.35, P=0.991, respectively).
This subanalysis of the TWILIGHT study showed that after 3 months DAPT following PCI with a drug-eluting stent, ticagrelor monotherapy compared to continuation of ticagrelor plus aspirin lowered the risk of BARC 2, 3, or 5 bleeding without increasing ischemic events up to a follow-up of 12 months in patients with and without high bleeding risk.