Ticagrelor monotherapy lowers bleeding risk vs DAPT in high-risk patients
The TWILIGHT trial demonstrated that switching to ticagrelor monotherapy after 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin significantly lowered the incidence of bleeding compared with staying on DAPT, without increasing the risk of ischaemic events. Data from two substudies, TWILIGHT-DM and TWILIGHT-Complex, presented at the American College of Cardiology and World Congress of Cardiology 2020 virtual meeting (ACC/WCC 2020), showed consistent findings in patients with diabetes mellitus (DM) and patients who underwent complex percutaneous coronary intervention (PCI).
TWILIGHT-DM: Ticagrelor monotherapy reduces bleeding vs DAPT in DM patients
The prespecified TWILIGHT-DM substudy focused on the 2,620 patients with DM, who constituted 36.8 percent of all high-risk PCI patients of the TWILIGHT trial. Patients were treated with DAPT using ticagrelor plus aspirin for 3 months following PCI, after which event-free and adherent patients were randomized to receive DAPT (n=1,301) or ticagrelor (90 mg BID) plus placebo (n=1,319) for an additional 12 months. Of note, a quarter of DMpatients were enrolled in Asia. [J Am Coll Cardiol 2020, doi: 10.1016/j.jacc.2020.03.008]
“The DM patients had a high prevalence of chronic kidney disease [20.3−22.0 percent]; over 60 percent had acute coronary syndrome [ACS] at presentation, and nearly 30 percent had MI, representing a very high-risk population. Multivessel disease was present in almost 70 percent of patients, with a mean lesion length close to 40 mm,” said investigator Dr Dominick Angiolillio of the Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida, US.
In the intention-to-treat (ITT) cohort, the cumulative incidence of Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding was 6.7 percent in the DAPT group vs 4.5 percent in the ticagrelor monotherapy group (hazard ratio [HR], 0.65; 95 percent confidence interval [CI], 0.47 to 0.91; p=0.01). (Figure 1)
“Comparative data on the primary endpoint [BARC 2, 3 or 5 bleeding] among diabetic and non-diabetic patients showed an interaction p value of 0.23, supporting consistency of findings between the two cohorts,” highlighted Angiolillo.
In the per-protocol cohort, the cumulative incidence of ischaemic events (death, MI or stroke) at 12 months was 5.9 percent in the DAPT group vs 4.6 percent in the ticagrelor monotherapy group (HR, 0.77; 95 percent CI, 0.55 to 1.09; p=0.14). “We also conducted an exploratory, non-prespecified analysis of net adverse clinical events of most severe [BARC 3 or 5] bleeding, death, MI, or stroke in the ITT cohort. The cumulative incidence at 12 months was 8.7 percent with DAPT vs 5.4 percent with ticagrelor monotherapy, with a HR of 0.61 [95 percent CI, 0.45 to 0.82; p=0.001] and a number needed to treat [NNT] of 30,” added Angiolillo.
“Compared with ticagrelor plus aspirin, ticagrelor monotherapy showed a consistent effect in reducing the risk of clinically relevant bleeding without any increase in ischaemic events among patients with or without DM undergoing PCI,” concluded Angiolillo. “This bleeding avoidance strategy can be implemented without any signal of harm even in high-risk groups, such as DM patients.”
TWILIGHT-Complex: Single-agent ticagrelor lowers bleeding after complex PCI
The TWILIGHT-Complex substudy included 2,620 patients who underwent complex PCI in the TWILIGHT trial. After 3 months of post-PCI DAPT, 1,158 patients were randomized to receive ticagrelor (90 mg BID) plus placebo, while 1,184 received ticagrelor plus aspirin. Of note, 26.9 percent of the TWILIGHT-Complex patients were enrolled in Asia. [J Am Coll Cardiol 2020, doi: 10.1016/j.jacc.2020.03.011]
“At 12 months, the primary outcome of moderate or severe bleeding, as defined by BARC 2, 3 or 5, occurred in 4.2 percent of patients in the ticagrelor monotherapy arm vs 7.7 percent of those in the ticagrelor plus aspirin arm [HR, 0.54; 95 percent CI, 0.38 to 0.76]. The effect of ticagrelor monotherapy was consistent between complex and non-complex PCI groups [pinteraction=0.79],” reported investigator Dr George Dangas of Icahn School of Medicine at Mount Sinai, New York, New York, US. (Figure 2)
In the per-protocol cohort, the ischaemic endpoint of death, MI or stroke occurred in 3.8 percent of patients in the ticagrelor monotherapy group vs 4.9 percent of those in the DAPT group (HR, 0.77; 95 percent CI, 0.52 to 1.15).
Sensitivity analysis was performed across various components of complex PCI to evaluate whether ticagrelor monotherapy was particularly favourable or unfavourable in any of the groups. “The atherectomy group did somewhat better on single-agent ticagrelor in terms of death, MI or stroke, but overall, there were few differences between the treatment arms. None of the groups appeared to specifically benefit from ticagrelor plus aspirin,” said Dangas.
“Among patients who underwent complex PCI, as defined by a combination of high-risk angiographic and procedural features, ticagrelor monotherapy [after an initial 3 months of DAPT with ticagrelor plus aspirin] was associated with significantly lower clinically relevant bleeding vs continuous DAPT, without increasing the risk of ischaemic events,” concluded Dangas. “This effect was consistent across individual components of the complex PCI definition.”