SAN FRANCISCO – After 3 months of ticagrelor (Brilinta) plus aspirin following cardiac stenting, stopping the aspirin but continuing the ticagrelor resulted in less bleeding with no increase in ischemic events in a randomized trial with more than 7,000 drug-eluting stent patients at high risk for both.
Dr. Roxana Mehran
“This was a superior therapy” to staying on both drugs, the more usual approach, said lead investigator Roxana Mehran, MD, director of interventional cardiovascular research and clinical trials at the Icahn School of Medicine at Mount Sinai, New York.
“We can’t say this is for all comers, but for patients whose physician felt comfortable putting them on aspirin and ticagrelor,” who tolerated it well for the first 3 months, and who had clinical and angiographic indications of risk, “I think these patients can be peeled away” from aspirin, she said in a presentation at the Transcatheter Cardiovascular Therapeutics annual meeting that coincided with publication of the trial, dubbed TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention).
Interventional cardiologists have long sought the sweet spot for dual-antiplatelet therapy (DAPT) after stenting; the idea is to maximize thrombosis prevention while minimizing bleeding risk. The trial supports the trend in recent years towards shorter DAPT. Often, however, it’s the P2Y12 inhibitor – ticagrelor, clopidogrel (Plavix), or prasugrel (Effient) – that goes first, not the aspirin.
Responding to an audience question about why the trial didn’t include an aspirin monotherapy arm, Dr. Mehran said that aspirin alone wouldn’t have been sufficient in high-risk patients “in whom you have almost 70% acute coronary syndrome.” She added that her team has data showing that aspirin itself doesn’t have much effect on blood thrombogenicity.
The 7,119 patients in TWILIGHT were on ticagrelor 90 mg twice daily and aspirin 81-100 mg daily for 3 months, then evenly randomized to continued treatment or ticagrelor plus an aspirin placebo for a year.
Subjects had to have at least one clinical and angiographic finding that put them at high risk for bleeding or an ischemic event, such as chronic kidney disease, acute coronary syndrome, diabetes, or a bifurcated target lesion treated with two stents.
One year after randomization, 4% in the ticagrelor monotherapy group versus 7.1% in the ticagrelor plus aspirin arm reached the primary end point, actionable (type 2), severe (type 3), or fatal (type 5) bleeding on the Bleeding Academic Research Consortium scale (hazard ratio, 0.56; 95% confidence interval, 0.45 - 0.68, P less than .001).
The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (HR, 0.99; 95% CI, 0.78-1.25; P less than .001 for noninferiority).
There were more ischemic strokes in the ticagrelor monotherapy arm (0.5% versus 0.2%). All-cause mortality (1.3% versus 1%) and stent thrombosis (0.6% versus 0.4%) were more frequent in the ticagrelor/aspirin group, but the differences were not statistically significant.
The two groups were well balanced. The mean age was 65 years, 23.8% of the patients were female, 37% had diabetes, and 65% had percutaneous coronary intervention for an acute coronary syndrome. Almost two-thirds had multivessel disease. Mean stent length was about 40 mm. The trial excluded patients with prior strokes.
Almost 2,000 patients originally enrolled in the trial never made it to randomization because they had a major bleeding or ischemic event in the 3-month run up, or dyspnea or some other reaction to ticagrelor.
The recent STOPDAPT-2 trial had a similar outcome – less bleeding with no increase in ischemic events – with clopidogrel monotherapy after a month-long run in of dual therapy with aspirin, versus continued treatment with both, in patients at low risk for ischemic events after stenting (JAMA. 2019 Jun 25;321[24]:2414-27).
Another recent study, GLOBAL LEADERS, concluded that 1 month of DAPT followed by ticagrelor monotherapy for 23 months was not superior to 12 months of DAPT followed by a year of aspirin. There was a numerical advantage for solo ticagrelor on death, myocardial infarction, and bleeding, but it did not reach statistical significance (Lancet. 2018 Sep 15;392[10151]:940-9).
The work was funded by ticagrelor’s maker, AstraZeneca. Dr. Mehran reported consulting and other relationships with Abbott, Janssen, and other companies.
SOURCE: Mehran A et al. N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419.