Introduction and methods

Safety And Efficacy Of Ticagrelor Monotherapy After Complex PCI: The TWILIGHT-COMPLEX Substudy

Presented at ACC.20 by George D. Dangas, MD, PhD (New York, NY, USA)

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor reduces the risk of thrombotic events in patients who underwent percutaneous coronary intervention (PCI), but also increases the risk of bleeding events. There is a need for an antiplatelet therapy regimen that reduces risk of bleeding while preserving efficacy in patients with extensive coronary artery disease undergoing complex PCI. The TWILIGHT trial showed that after 3 month-treatment with DAPT, ticagrelor monotherapy resulted in reduced bleeding without increase ischemic events compared to continued use of ticagrelor and aspirin after 12 months in high risk patients following PCI. The TWILIGHT-COMPLEX substudy is a secondary analysis of the TWLIGHT trial and examined the safety and efficacy of ticagrelor monotherapy vs. ticagrelor plus aspirin in high risk patients undergoing complex PCI.

2342 Patients who underwent complex PCI (defined as: 3 vessels treated, ≥3 lesions treated, total stent length >60 mm, bifurcation with 2 stents implanted, use of any atherectomy device, left main PCI, surgical bypass graft, or chronic total occlusion as target lesion) were initially treated with ticagrelor plus aspirin for 3 months after PCI. Adherent patients without major bleeding or ischemic events after 3 months were randomized to receive either ticagrelor plus aspirin or ticagrelor plus placebo for 1 year.

The primary endpoint was BARC type 2, 3, or 5 bleeding and the key secondary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke, 1 year after randomization.

Main results

• Patients who were treated with ticagrelor plus placebo had lower rates of the primary endpoint of BARC type 2, 3 or 5 bleeding, compared to patients on ticagrelor plus aspirin (4.2% vs. 7.7%, HR 0.54, 95%CI 0.38-0.76)

• Severe bleeding (BARC type 3 or 5) was also less prevalent in patients on ticagrelor plus placebo compared to those on ticagrelor plus aspirin (1.1% vs. 2.6%, HR 0.41, 95%CI 0.21-0.80).

• There was no significant difference in the composite endpoint of all-cause death, MI or stroke between the ticagrelor plus placebo group compared to the ticagrelor plus aspirin group (3.8% vs. 4.9%, HR 0.77; 95%CI 0.52-1.15).

• There was no significant statistical interaction for treatment effects on bleeding and ischemic endpoints between patients with complex PCI and those with non-complex PCI.

Conclusion

After an initial treatment period with ticagrelor plus aspirin for 3 months post-PCI, treatment with ticagrelor monotherapy was associated with lower rates of BARC 2, 3 of 5 bleeding events without increasing the risk of ischemic events compared to treatment with ticagrelor plus aspirin in patients who underwent complex PCI.

Discussion

The discussant Claire Duvernoy, MD (Ann Arbor, MI, USA) referred to an important comment that was made earlier: How can it be that this trial gives such different results compared to other trials that investigated extended use of DAPT? There are two important differences between the TWILIGHT trial and those other trials, according to Duvernoy. The TWILIGHT trial dropped aspirin, instead of the newer P2Y12 inhibitor, and used second generation stents, which are much safer compared to older stents.

- Our coverage of ACC.20 is based on the information provided during the congress –

The results were simultaneously published in J. Am. Coll. Cardiol