Reduced bleeding with P2Y12i monotherapy in high risk, PCI-treated patients
Ticagrelor with or without Aspirin in High-Risk Patients after PCI
Literature - Mehran R, Baber U, Sharma SK, et al. - N Engl J Med 2019, DOI: 10.1056/NEJMoa1908419Introduction and methods
Use of more potent P2Y12 inhibitors, such as ticagrelor, or extended duration of dual antiplatelet therapy (DAPT) reduces ischemic risk in patients with enhanced thrombotic risk, but this comes at the expense of increased bleeding risk {1-4]. Post-PCI bleeding should not be considered benign, as it is associated with a substantial and durable increased risk of mortality [5-7]. Strategies to lower bleeding risk with preservation of ischemic benefit involve shortening of DAPT with early withdraw of P2Y12 inhibition [8-10], or withdrawal of aspirin use to prevent aspirin-related bleedings [11].
The Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) trial evaluated whether ticagrelor monotherapy would be superior to DAPT in reducing clinically relevant bleeding without an increase in ischemic risk in high risk patients after PCI and who had completed 3-months of DAPT with ticagrelor and aspirin.
This was a randomized, placebo-controlled, double-blind clinical trial. Eligible patients had to have at least one additional clinical feature and one angiographic feature associated with a high risk of ischemic or bleeding events. All patients received ticagrelor and aspirin after PCI. Three months after hospital discharge, 7119 patients without major bleeding event or ischemic event were randomized to receive aspirin or placebo in addition to ticagrelor for an additional 12 months.
Primary endpoint was first occurrence of BARC type 2, 3 or 5 bleeding. Key secondary endpoint was first occurrence of death from any cause, nonfatal MI or nonfatal stroke.
Main results
- In the ticagrelor monotherapy group, 4.0% of patients experienced the primary endpoint compared to 7.1% of patients in the DAPT group (HR: 0.56, 95%CI: 0.45-0.68, P<0.001).
- BARC type 3 or 5 bleeding occurred in 1.0% of the patients in the ticagrelor monotherapy group and in 2.0% in the DAPT group (HR: 0.49, 95%CI:0.33 -0.74).
- Ischemic events were analyzed in the per-protocol population (according to plan [12]), including 7039 patients. In the ticagrelor monotherapy group, 3.9% experienced the key secondary endpoint of death from any cause, nonfatal MI or nonfatal stroke, and this was similar in the DAPT group (also 3.9%) (HR: 0.99, 95%CI: 0.78-1.25).
Conclusion
The TWILIGHT trial showed that in high risk patients following PCI and 3 month-treatment with ticagrelor and aspirin, ticagrelor monotherapy resulted in reduced bleeding without ischemic harm compared to continued use of ticagrelor and aspirin after 12 months.
References
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