Comparative study finds higher rates of adverse events with ticagrelor

One year of treatment with either of two strong blood-thinning medications - ticagrelor and prasugrel - by people with type 1 or type 2 diabetes who had a drug-eluting stent placed in their heart to treat coronary artery blockages did not offer the same level of benefit to prevent stent clotting, heart attacks, and bleeding complications, according to findings presented during a preliminary late-breaking science session during the American Heart Association's Scientific Sessions 2025 in New Orleans on November 10.

"Our results suggest that prasugrel may be the better choice for patients with type 1 or type 2 diabetes," said study lead author Sripal Bangalore, MD, director of research at NYU Langone's Cardiac Catheterization Laboratory and in the Department of Medicine's Leon H. Charney Division of Cardiology at NYU Grossman School of Medicine.

The results were unexpected, as we initially hypothesized that ticagrelor would be equally effective, if not better, than prasugrel. These findings highlight the importance of selecting the right medication, as our data indicate that ticagrelor and prasugrel are not interchangeable."

Sripal Bangalore, Cardiac Catheterization Laboratory, NYU Langone

The TUXEDO-2 study is a randomized clinical trial designed to evaluate strategies for treating coronary artery disease among 1,800 adults in India with type 1 or type 2 diabetes and multivessel disease. The trial focused on stent selection, revascularization techniques, antiplatelet therapy, and other approaches. All participants received one of two specific drug-eluting stents during a percutaneous coronary intervention to open a blocked artery and restore blood flow. These stents are coated with medication to help prevent the treated vessel from narrowing again.

This part of the study specifically focused on comparing the antiplatelet medications prasugrel and ticagrelor, which were prescribed to the patients, along with aspirin, after the stent procedure. Dr. Bangalore and the research team reviewed the rate of stroke, heart attack, bleeding complications, and death after one year of the medication regimens.

Study findings:

• The primary combined outcome of heart attack, stroke, bleeding complications, and death occurred at a 16.57 percent rate in patients taking ticagrelor compared to 14.23 percent in those taking prasugrel.
• Nonfatal heart attacks occurred in 5.96 percent of the ticagrelor group versus 5.21 percent of the prasugrel group, while major bleeding events were reported in 8.41 percent of ticagrelor patients compared to 7.14 percent in those who used prasugrel. Death rates were also higher for ticagrelor patients, at 5.03 percent, compared to 3.67 percent for patients taking prasugrel.
• Worse outcomes were observed with ticagrelor in patients with diabetes duration of less than five years (HR=1.63; 95% CI 1.10-2.42) and in those with a high risk of bleeding (HR=1.61; 95% CI 1.02-2.53).

"These medications are often considered interchangeable, but our findings suggest important differences," said Dr. Bangalore. "For individuals with type 1 or type 2 diabetes and complex coronary disease, prasugrel may offer distinct advantages over ticagrelor. This research highlights the need for a more personalized approach to treatment, as the two drugs should not be used interchangeably."

Dual antiplatelet therapy, combining aspirin and a P2Y12 inhibitor medication, plays a crucial role in preventing blood clots and reducing the risk of serious heart-related events in people with acute coronary syndrome. According to the "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes," continued dual antiplatelet therapy is recommended for at least one year for all patients who receive a drug-eluting stent.

Study details, background, and design:

• The TUXEDO-2 study was conducted at 66 healthcare sites across India. Enrollment for the trial was conducted from 2020 to 2024, and the study researchers assessed participants' outcomes after they had been randomly assigned to receive one of the two types of stents, as well as two types of dual antiplatelet therapy.
• The study included 1,800 adults (the average age was 60; 71 percent were men and 29 percent were women) with type 1 or type 2 diabetes and multivessel coronary disease who underwent percutaneous coronary intervention (to restore blood flow to the artery) and a drug-eluting stent was implanted.
• About one-quarter of the study participants were taking insulin, roughly 79 percent had acute coronary artery syndrome, and approximately 85 percent had triple vessel disease.
• The primary clinical trial is evaluating the safety and efficacy of percutaneous coronary intervention with two drug-eluting stents in patients with type 1 or type 2 diabetes and multivessel coronary disease. The objective of this analysis was a randomized comparison of ticagrelor versus prasugrel, in addition to aspirin, to assess potential impact on heart attack, stroke, major bleeding, complications and death.
• The two patient groups were similar across age, sex, ethnicity, and heart health status.
• The trial is ongoing and will continue to follow these patients for approximately five years after stent implantation.

Study limitations included that both patients and physicians were aware of the assigned medications, which could introduce bias. Additionally, treatment compliance was not monitored, so it's unclear whether participants consistently took their medications as prescribed.