Prasugrel outperforms ticagrelor in diabetic stent patients, study finds

Cardiologists have long treated two powerful blood-thinning medications as essentially interchangeable when it comes to protecting diabetic patients after stent placement. A major clinical trial presented this week at the American Heart Association's annual meeting in New Orleans suggests that assumption may be wrong.

The TUXEDO-2 study, which enrolled 1,800 adults with Type 1 or Type 2 diabetes across 66 health care sites in India between 2020 and 2024, compared prasugrel and ticagrelor—both P2Y12 inhibitors given alongside aspirin to prevent blood clots after a drug-eluting stent is placed in a narrowed coronary artery. After one year, the results diverged in ways that surprised even the researchers. Patients taking ticagrelor experienced the primary composite outcome of heart attack, stroke, major bleeding, or death at a rate of 16.57 percent. Those on prasugrel had that outcome at 14.23 percent—a meaningful difference in a population already at high risk.

The gap widened when researchers looked at individual complications. Non-fatal heart attacks occurred in 5.96 percent of the ticagrelor group versus 5.21 percent in the prasugrel group. Major bleeding happened in 8.41 percent taking ticagrelor compared to 7.14 percent on prasugrel. Death rates were 5.03 percent with ticagrelor and 3.67 percent with prasugrel. Sripal Bangalore, the lead researcher and a professor of medicine at NYU Grossman School of Medicine, said the findings contradicted the team's initial hypothesis. "We were surprised by the results because we hypothesized that ticagrelor should be as good or perhaps even better than prasugrel," Bangalore said. "It's important to choose the right medicine, and at least from our data, we cannot say that ticagrelor and prasugrel are interchangeable."

The study population was predominantly male (71 percent) with an average age of 60. About a quarter were insulin-dependent, roughly 79 percent had acute coronary artery syndrome, and approximately 85 percent had triple vessel disease—meaning blockages in all three major coronary arteries. These were, in other words, among the sickest cardiac patients, the ones with the most complex disease and the highest stakes for treatment decisions.

Current guidelines from the American College of Cardiology and American Heart Association recommend at least one year of dual antiplatelet therapy—aspirin plus a P2Y12 inhibitor—for all patients after drug-eluting stent placement. The medications work by preventing platelets from clumping together and forming clots that could block the stent or trigger a heart attack. But which P2Y12 inhibitor to choose has been treated as largely a matter of clinical preference or patient tolerance, with the two drugs considered functionally equivalent.

Bangalore emphasized that the findings challenge this equivalence. "Currently, these medications are treated as interchangeable. However, our findings provide evidence that they might be a bit different," he said. "For individuals with Type 1 or Type 2 diabetes and complex coronary disease, there may be an advantage to treatment with prasugrel over ticagrelor, and importantly, the two should not be used interchangeably."

The study does carry limitations worth noting. Patients and their physicians knew which medication was being assigned, which could introduce bias. The researchers had no way to verify that patients actually took their medications as prescribed. And because the trial was conducted only in India, the findings may not directly apply to other health systems or populations with different genetic backgrounds or disease patterns. The main TUXEDO-2 trial will continue following patients for five years, potentially offering longer-term insight into whether these differences persist or shift over time.