Ticagrelor was not shown to be noninferior to prasugrel for the reduction of the primary composite endpoint of death, nonfatal myocardial infarction (MI), stroke or major bleeding at one year in patients with diabetes and multivessel coronary disease (MVD) undergoing PCI, according to results from TUXEDO-2, conducted by Sripal Bangalore, MD, FACC, et al., and published Feb. 11 in JAMA Cardiology.

At 66 clinical sites across India, this investigator-initiated, open-label trial randomized 1,800 patients with diabetes (mean age 60; 28% women; 24% receiving insulin therapy) and MVD (85% with triple-vessel disease) to PCI with either the ultrathin biodegradable polymer-coated Supraflex Cruz sirolimus-eluting stent or a durable polymer-coated Xience everolimus-eluting stent. All patients received low-dose aspirin and were also randomized to ticagrelor or prasugrel.

Results at one year showed that a primary outcome event occurred in 17% of patients in the ticagrelor group vs. 14% of the prasugrel group (hazard ratio [HR], 1.22; p=0.12). The between-group difference did not meet the prespecified threshold of noninferiority (p=0.84).

Although not statistically significant, in the ticagrelor vs. the prasugrel group, there was a numerically higher rate of the composite of death/MI/stroke (10.43% vs. 8.63% prasugrel; p=0.30) and major bleeding (8.41% vs. 7.14%; p=0.19). Other outcomes were similar between the two groups including all-cause death (5.0% vs. 3.7%) and nonfatal MI (6.0% vs. 5.2%), definite or probable stent thrombosis (1.1% vs. 0.6%) and acute stent thrombosis (4 vs. 0 events).

Additionally, two subgroups experienced an excess of the primary outcome: patients with a diabetes duration <5 years (HR, 1.63) and those with high bleeding risk (HR, 1.61). No subgroup showed evidence of benefit with ticagrelor.

"Our findings suggest that prasugrel can offer a favorable balance between efficacy and safety," write the authors. They note that clinical decision-making could be influenced by "practical factors" with ticagrelor such as twice-daily dosing, higher incidence of dyspnea, and adherence challenges.

They conclude that this trial did not demonstrate that ticagrelor was noninferior in this patient population, "thus leaving uncertainty as to whether a prasugrel-based strategy is superior."