Ticagrelor with Aspirin or Alone in High-Risk Patients After Intervention for Acute Coronary Syndrome

Educational Objectives

After completing the activity, the clinician will be better able to summarize the results of the TWILIGHT substudy comparing ticagrelor with or without aspirin for extended antiplatelet therapy in high-risk patients after stenting for acute coronary syndrome (TWILIGHT ACS).

Summary

Interviewer: Spencer B. King III, MD, MACC, Atlanta, GA

Take-home Messages:

• For select patients following percutaneous coronary intervention (PCI), several recent trials have suggested that aspirin-free antiplatelet strategies lower risk for bleeding without increasing ischemic risk compared to conventional dual antiplatelet therapy (DAPT).
• TWILIGHT ACS extends earlier findings supporting aspirin-free antiplatelet therapy to high-risk patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) or unstable angina (UA) — specifically, for those with both high-risk clinical and angiographic features.
• After an initial 3-month period of DAPT with ticagrelor plus aspirin, TWILIGHT ACS demonstrated that continuation of antiplatelet therapy with ticagrelor monotherapy significantly reduced bleeding without increasing ischemic risk compared to ticagrelor plus aspirin.

Dual antiplatelet therapy became the preferred treatment for patients with acute coronary syndromes (ACS) based on clinical trials demonstrating that the addition of an oral P2Y12 inhibitor to aspirin significantly lowered recurrent ischemic events compared with aspirin alone.

While long-term aspirin is a simple and inexpensive therapy, the benefits, or harms, of maintaining aspirin as a long-term component of DAPT remains unknown, given that aspirin served as background therapy in earlier studies.

While the risk of aspirin-related bleeding has been known for decades, it was considered a relatively benign problem — until post-PCI bleeding was shown to be associated with a substantial and durable risk of death, approximating or even exceeding that associated with myocardial infarction.

In 2019, data from 3 trials — GLOBAL LEADERS, STOPDAPT-2, and SMART-CHOICE — suggested that aspirin-free strategies lower bleeding without increasing ischemic risk compared to conventional DAPT in certain patients (such as those at high risk for bleeding or an ischemic event) following PCI.

Now we can add a fourth trial to the list: TWILIGHT ACS evaluated the effect of antiplatelet monotherapy with ticagrelor compared to ticagrelor plus aspirin among patients with NSTE-ACS or UA undergoing PCI with drug-eluting stents. All patients were required to have one high-risk clinical and angiographic feature; in actuality, about half had ≥ 4 high-risk clinical or angiographic features.

After completing a 3-month course of DAPT, event-free and adherent patients were randomized to aspirin plus ticagrelor or continuation of ticagrelor (plus placebo) for an additional year.

The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding.

The TWILIGHT of Aspirin?

The ACS analysis comes from the overall TWILIGHT trial, which enrolled 7,119 patients, including individuals with stable angina and asymptomatic patients.¹ The specific analysis of NSTE-ACS and UA patients was known as TWILIGHT-ACS.

After 3 months of ticagrelor-based DAPT, all patients without events who remained adherent to therapy underwent randomization. Twelve months after randomization, the incidence of the primary endpoint was significantly lower among patients randomly assigned to receive ticagrelor plus placebo than those randomized to ticagrelor plus aspirin (p < 0.001) (Table). Bleeding risk was cut in half with ticagrelor monotherapy, and the treatment effect was consistent across predefined subgroups.

TWILIGHT-ACS: Primary and Select Secondary Endpoints

	Ticagrelor + Placebo (n = 2,269)	Ticagrelor + Aspirin (n = 2,338)	Hazard Ratio (95% CI)
Primary endpoint*	3.6%	7.6%	0.47 (0.36-0.61)
Ischemic endpoints
All-cause death, nonfatal MI, or nonfatal stroke	4.3%	4.4%	0.97 (0.74-1.28)
Stent thrombosis, definite or probable	0.4%	0.6%	NA (p = 0.38)

*Bleeding Academic Research Consortium type 2, 3, or 5 bleeding.

CI = confidence interval; MI = myocardial infarction.

There was no significant clinical cost to dropping the aspirin, with no difference in the key secondary composite endpoint of death from any cause, nonfatal myocardial infarction, or nonfatal stroke (p for noninferiority: < 0.001) (Table).

Thus, TWILIGHT-ACS demonstrates that, after a 3-month course of DAPT with ticagrelor plus aspirin, continued treatment with ticagrelor alone significantly lowered clinically relevant and major bleeding without increasing risk for ischemic events over the next year.

The effect of ticagrelor monotherapy with respect to bleeding and ischemic events was uniform across different levels of risk. Results were similar whether patients presented with UA or NSTEMI, and all results were concordant with the main study results.

The authors caution that extrapolating the results to patients with ST-segment elevation myocardial infarction (STEMI) is not possible because the trial design placed STEMI among the exclusion criteria. Also, it is not appropriate to generalize the results to a broader population of PCI patients without the prespecified high-risk features of those enrolled in TWILIGHT.

Reference:

1. Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or Without Aspirin in High-Risk Patients After PCI. N Engl J Med 2019;381:2032-42.

Readings

Disclosures

Usman Baber, MD, New York, NY

This author has nothing to disclose.

Interviewer: Spencer B. King III, MD, MACC, Atlanta, GA

This author has nothing to disclose.

Acknowledgements

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

AC520317

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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