Ticagrelor monotherapy beneficial in complex PCI, diabetes: New TWILIGHT data

ByErik Swain

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George D. Dangas

In new findings from the TWILIGHT trial of patients who underwent PCI, switching from dual antiplatelet therapy to ticagrelor monotherapy after 3 months benefited patients who had complex PCI and patients with diabetes.

As Healio previously reported, in the main results of TWILIGHT, among patients who underwent PCI with a drug-eluting stent and were on ticagrelor (Brilinta, AstraZeneca) plus aspirin for 3 months, those who switched to ticagrelor monotherapy had reduced risk for Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding at 1 year compared with those who stayed on DAPT, without elevated ischemic risk.

TWILIGHT-COMPLEX

In the new TWILIGHT-COMPLEX trial, George D. Dangas, MD, PhD, FACC, FAHA, MSCAI, professor of medicine and surgery at Icahn School of Medicine at Mount Sinai and director of cardiovascular innovation at the Cardiovascular Institute of the Mount Sinai Medical Center, analyzed 2,342 patients from TWILIGHT (mean age, 66 years; 21% women) who underwent complex PCI, which was defined as three vessels treated, at least three lesions treated, total stent length of more than 60 mm, bifurcation with two stents implanted, use of atherectomy, left main PCI, a surgical bypass graft target lesion or a chronic total occlusion target lesion.

“The main TWILIGHT trial introduced in a placebo-controlled manner that discontinuing aspirin after 3 months offers benefits in reducing bleeding without increased risk in ischemic event prevention,” Dangas said during a virtual American College of Cardiology Scientific Sessions presentation. “The natural question of this trial would be if that is true in the patients who had the most complex PCI. Hence, we undertook this investigation, which is a post hoc analysis, specifically in patients with complex PCI.”

In this population, the ticagrelor monotherapy group had lower risk for BARC type 2, 3 or 5 bleeding at 1 year compared with the ticagrelor plus aspirin group (4.2% vs. 7.7%; absolute risk difference, –3.5 percentage points; HR = 0.54; 95% CI, 0.38-0.76), according to the researchers.

BARC type 3 or 5 bleeding was also lower in the ticagrelor monotherapy group than in the DAPT group (1.1% vs. 2.6%; absolute risk difference, –1.5 percentage points; HR = 0.41; 95% CI, 0.21-0.8), Dangas said.

There was no difference between the groups in death/MI/stroke (monotherapy, 3.8%; DAPT, 4.9%; absolute risk difference, –1.1 percentage points; HR = 0.77; 95% CI, 0.52-1.15) or CV death/MI/ischemic stroke (monotherapy, 3.6%; DAPT, 4.8%; absolute risk difference, –1.2 percentage points; HR = 0.75; 95% CI, 0.5-1.12), he said.

There were also no between-group differences in all-cause death (monotherapy, 0.9%; DAPT, 1.5%; absolute risk difference, –0.6 percentage points; HR = 0.59; 95% CI, 0.27-1.29) or definite or probable stent thrombosis (monotherapy, 0.4%; DAPT, 0.8%; absolute risk difference, –0.4 percentage points; HR = 0.56; 95% CI, 0.19-1.67), the researchers found.

In addition, Dangas said, there was no interaction of the treatment effect of monotherapy on bleeding or ischemic events between those who underwent complex PCI and those who did not.

The bleeding benefit and lack of ischemic harm from ticagrelor monotherapy “was consistent across the individual components of the complex PCI definition,” Dangas said.

“We did show that in patients who underwent complex PCI ... monotherapy was associated with highly clinically relevant lower bleeding, without an increase in the risk of ischemic events compared to continued DAPT,” he said.

The TWILIGHT-COMPLEX analysis was published simultaneously in the Journal of the American College of Cardiology.

TWILIGHT-DM

Dominick J. Angiolillo

For TWILIGHT-DM, Dominick J. Angiolillo, MD, PhD, professor of medicine, director of cardiovascular research and director of the Interventional Cardiology Fellowship Program at the University of Florida Health System, analyzed 2,620 patients from TWILIGHT who had diabetes (mean age, 65 years; 24% women).

Compared with those without diabetes, patients with diabetes had more comorbidities and were more likely to have multivessel disease, Angiolillo said during his virtual presentation.

“After the very exciting results from the TWILIGHT trial, it obviously becomes of interest to understand if this antithrombotic strategy remains effective in patient cohorts at particularly high risk, such as patients with diabetes,” he said.

In the diabetes population, BARC type 2, 3 or 5 bleeding was lower at 1 year in those assigned ticagrelor monotherapy than in those assigned DAPT (4.5% vs. 6.7%; HR = 0.65; 95% CI, 0.47-0.91), and the treatment effect was similar to that observed in the nondiabetes cohort (P for interaction = .23), he said, noting that the same was true for other measures of bleeding.

All-cause death/MI/stroke was similar between the groups (monotherapy, 4.6%; DAPT, 5.9%; HR = 0.77; 95% CI, 0.55-1.09), according to the researchers. Angiolillo said there was no difference between the groups in any type of ischemic event.

In an exploratory analysis, net adverse clinical events, defined as BARC type 3 or 5 bleeding, death, MI or stroke, were lower in those with diabetes assigned ticagrelor monotherapy than in those assigned DAPT (5.4% vs. 8.7%; HR = 0.61; 95% CI, 0.45-0.82; number needed to treat, 30), Angiolillo said.

“Compared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without diabetes undergoing PCI,” Angiolillo said during the presentation. “Overall, these findings support such a bleeding avoidance strategy, which can be implemented without any signals for harm even in high-risk patients such as those with diabetes.”

The TWILIGHT-DM analysis was also published simultaneously in JACC. – by Erik Swain

References:

Angiolillo DJ, et al.

Dangas GD, et al. Late-Breaking Clinical Trials IV. Both presented at: American College of Cardiology Scientific Session; March 28-30, 2020 (virtual meeting).

Angiolillo DJ, et al. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2020.03.008.

Dangas GD, et al. J Am Coll Cardiol. 2020;doi:10.1016/j.jacc.2020.03.011.

Disclosures: TWILIGHT was funded by AstraZeneca. Angiolillo reports he received consultant fees/honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, CeloNova, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi and The Medicines Company, and received institutional research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, RenalGuard Solutions and Spartan. Dangas reports he consulted for Abbott Vascular, Boston Scientific and Biosensors, formerly owned common stock in Medtronic and received institutional research grants from AstraZeneca, Bayer and Daiichi Sankyo. Please see the studies for all other authors’ relevant financial disclosures.