Switching to P2Y12 monotherapy after DAPT lowers bleeding risk in high-risk NSTE-ACS patients

AHA 2019 In patients with NSTE-ACS undergoing PCI with DES, ticagrelor monotherapy after 3 months of DAPT, significantly lowered major bleeding without increasing risk for ischemic events.

Presented during the AHA Scientific Sessions 2019 by Usman Baber (Icahn Sch of Med at Mount Sinai, New York, NY) .

Introduction and methods

The prevailing construct of dual antiplatelet therapy (DAPT) as the preferred treatment for patients with acute coronary syndromes (ACS) originated from clinical trials showing that the addition of an oral P2Y12 inhibitor to aspirin significantly lowers recurrent ischemic events as compared with aspirin alone. The benefits, or harms, of maintaining aspirin as a long-term component of DAPT in the setting of ACS remains unknown, however, as aspirin served as a background agent in earlier studies.

Recent studies have suggested that aspirin-free strategies lower bleeding without increasing ischemic risk as compared with conventional DAPT in select patients undergoing percutaneous coronary intervention (PCI).

The TWILIGHT-ACS study set out to examine the effect of antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin among patients with non-ST elevation acute coronary syndromes (NSTE-ACS) undergoing PCI with drug eluting stents (DES) who had already completed a 3-month course of DAPT. It was a randomized, double-blind placebo-controlled trial, in which high-risk patients underwent PCI and were treated with ticagrelor plus aspirin for three months. Event-free and adherent patients were then randomized to aspirin vs. placebo and continued ticagrelor for an additional year. After this period, they continued on standard of care for a 3 month observation period. 4614 Patients were randomized, 2494 of whom had unstable angina (UA) and 2120 of whom had NSTEMI. Primary endpoint was BARC 2, 3 or 5 bleeding between 0 - 12 months after randomization.

Main results

• BARC 2, 3 or 5 bleeding occurred ore often in the tica+aspirin group, as compared with those on tica+placebo (7.6% vs. 3.6%, HR: 0.47, 95%CI: 0.36-0.61, P<0.001).
• Stratified for number of risk factors, the HR’s were 0.49 (95%CI: 0.31-0.77) for those with 1-3 risk factors, HR: 0.50 (95%CI: 0.34-0.72) for those with 4 or 5 risk factors, and HR: 0.37 (95%CI: 0.20-0.68) for those with 6-9 risk factors (P-interaction: 0.69).
• Other bleeding endpoints, namely BARC 3 or 5, GUSTO moderate or severe and ISTH major bleeding also showed a significant better effect with ticagrelor monotherapy, while TIMI major bleed did not.
• The risk of death, MI or stroke did not significantly differ between ticagrelor monotherapy and combination therapy (HR: 0.97, 95%CI: 0.74-1.28, P=0.84). There was no significant interaction (P=0.18) with number of risk factor, although the point estimates varied from HR: 0.63, 95%CI: 0.33-1.22), to HR: 1.27 (95%CI: 0.83-1.93) and HR: 0.86 (95%CI: 0.54-1.36) for the respective groups (1-3, 4 or 5, 6-9 risk factors).
• Prespecified ischemic endpoints did not significantly differ between treatment groups.

Conclusion

Among patients with NSTE-ACS undergoing PCI with DES and who have completed a 3-month course of DAPT with ticagrelor plus aspirin, continued treatment with ticagrelor alone significantly lowers clinically relevant and major bleeding without increasing risk for ischemic events over one year. The effect of ticagrelor monotherapy with respect to bleeding and ischemic events was found to be uniform across different levels of risk.

Generalizing to a broader population of PCI patients without high-risk features pre-specified in TWILIGHT is limited and findings do not apply to patients with STEMI.

- Our reporting is based on the information provided during AHA Scientific Sessions 2019 -

Watch a video on this study by Usman Baber