P2Y12i alone reduces bleeding in CKD patients after PCI and 3 months DAPT

TWILIGHT-CKD: Ticagrelor monotherapy after PCI in high-risk patients with chronic kidney disease

Presented at the ESC congress 2020 by Carlo Briguori, MD, PhD (Napels, Italy)

Introduction and methods

Dual antiplatelet therapy (DAPT) is the standard combination therapy of aspirin and a P2Y12 inhibitor (such as ticagrelor) for the prevention of thrombotic complications in patients undergoing PCI. To decrease bleeding events in high-risk patients, discontinuation of aspirin early after PCI has emerged. Chronic kidney disease (CKD) patients have a high risk of bleeding and thrombotic events. It is unknown whether a strategy of early aspirin discontinuation reduced bleeding while maintaining adequate antithrombotic efficacy in patients with CKD after PCI.

The objective of the TWILIGHT-CDK study, a pre-specified analysis of the TWILIGHT trial, was to evaluate the efficacy and safety of ticagrelor monotherapy compared to ticagrelor plus aspirin in CKD patients undergoing PCI with drug-eluting stents after 3 months of DAPT.

TWILIGHT is a multicentered, randomized, double-blind placebo-controlled trial. In the TWILIGHT-CKD substudy, the effect of ticagrelor plus placebo compared to ticagrelor plus aspirin was examined in non-CKD (n=5690) and CKD (n=1145) patients (defined as eGFR <60 ml/min/1.73m² or CrCL <60 ml/min) were randomized to ticagrelor plus aspirin or ticagrelor plus placebo for 12 months. Primary outcome was BARC type 2, 3, or 5 bleeding. The secondary outcome was a composite of all-cause death, non-fatal MI, or stroke.

Patients eligible for inclusion had to meet at least one clinical and one angiographic criteria. Clinical inclusion criteria were: ≥65 years of age, female, ACS, CVD, diabetes mellitus with medication or insulin, or CKD. Angiographic criteria were: multivessel CAD, a target lesion requiring total stent length >30mm, thrombotic target lesion, bifurcation lesion(s) required ≥2 stents, left main ≥50% or proximal LAD ≥70% lesions, calcified target lesion(s) required atherectomy.

Main results

• Ticagrelor plus placebo outperformed ticagrelor plus aspirin in the CKD group, as well as in the non-CKD group for the primary outcome of BARC 2, 3 or 5 bleeding. Bleeding in the CKD group occurred in 4.4% of patients on ticagrelor plus placebo and in 8.9% of patients on ticagrelor plus aspirin (HR 0.48, 95% CI: 0.30-0.78, P=0.003). In non-CKD patients bleeding occurred in 4.0% of patients receiving ticagrelor and placebo compared to 6.7% of patients receiving ticagrelor and aspirin (HR 0.60, 95% CI: 0.47-0.75, P<0.001). There was no difference in the reduction of the primary end point by ticagrelor plus aspirin compared to ticagrelor plus placebo between the non-CKD and CKD patients (Pinteraction=0.44).
• There were no significant differences in the secondary outcome of all-cause death, non-fatal MI, or stroke between patients treated with ticagrelor and aspirin compared to those treated with ticagrelor and placebo. In the CDK group, the secondary outcome occurred in 7.7% of patients on ticagrelor plus placebo versus in 5.5% in patients on ticagrelor plus aspirin (HR 1.40, 95% CI: 0.88-2.22, P=0.16). In non-CDK patients, all-cause death, non-fatal MI, or stroke occurred in 3.2% of patients receiving ticagrelor and placebo compared to 3.6% of patients receiving ticagrelor and aspirin (HR 0.90, 95% CI: 0.68-1.2, P=0.48).

Conclusion

These results indicate that treatment with ticagrelor alone as compared to ticagrelor plus aspirin reduces the risk of bleeding events with no increased risk of thrombotic events in CKD patients after PCI.

- Our reporting is based on the information provided at the ESC congress -