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Ticagrelor alone vs. ticagrelor plus aspirin following percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: TWILIGHT-ACS

European Heart Journal (2020) 41, 3533–3545

Interventional Cardiology


To investigate the effect of Ticagrelor monotherapy in terms of clinically relevant bleeding and major ischemic events in patients presenting with unstable angina (UA) or non-STelevationMI (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) with drug eluting stents (DES) who had already completed a 3-month course of DAPT


A pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial was conducted.

Randomized, double-blind placebo controlled trial in 187 sites and 11countries.

Patients with high risk clinical and angiographic criteria and undergoing PCI were treated with ticagrelor plus aspirin for 3 months.

Event-free and adherent patients were randomized to aspirin versus placebo and continued ticagrelor for an additional year.

Primary endpoint: Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding between 0 -12 months after randomization

Key secondary outcome: a composite of all-cause death, myocardial infarction (MI), or stroke between 0 -12 months after randomization.


  • 4614 ACS patients were randomized
  • Ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36–0.61; P < 0.001)]
  • Rates of all cause death, MI, or stroke among did not differ between Ticagrelor plus Aspirin versus Ticagrelor plus placebo group (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74–1.28; P = 0.84)

Main messages

A dual antiplatelet treatment regimen with a platelet P2Y12 adenosine diphosphate (ADP) receptor antagonist in addition to the cyclooxygenase inhibitor acetylsalicylic acid (ASA) represents the cornerstone of treatment of ACS patients. However, the balance between protecting from ischemic events while avoiding bleeding complications following PCI is a major dilemma in current practice.

The new  faster-acting and more potent antiplatelet agents may justify revisiting the concept of aspirin as the cornerstone of DAPT.

More recently, numerous investigations are testing the hypothesis that acetylsalicylic acid-sparing regimens based on the availability of newer antithrombotic agents may increase net benefit for individual patients owing to the reduction in bleeding risk, without a trade-off in efficacy. Results from Twilight ACS trial showed that a transition to an antiplatelet strategy of treatment with Ticagrelor alone after a 3-month uneventful course of DAPT in high-risk patients who had undergone PCI provided a clinical benefit of less bleeding without ischemic harm.

At least two main issues of interest deserve further attention.

The authors underlined the 3-fold higher prevalence of Asians in the ACS population. Ethnicity is not enlisted among the high-bleeding risk (HBR) Academic Research Consortium consensus criteria, however the East-Asian paradox may have influenced the benefit of aspirin withdrawal.

One strategy fits all does not apply to the results of this trial, where a population with pre-specified high risk criteria was enrolled. However, the effect of ticagrelor monotherapy with respect to bleeding and ischemic events was uniform across different levels of risk and consistent among patients presenting with UA or NSTE-ACS.

The results of this study challenge the conventional paradigm of maintaining aspirin as a long-term component of DAPT among patients with NSTE-ACS undergoing PCI.

The optimal timing of aspirin withdrawal after PCI and whether these results would apply to a broader population warrant further investigations.


The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.