TLDR;
This video features an interview with Sweet Pal Bangalore, who discusses the Tuxedo 2 India trial, which compared prasugrel and ticagrelor in diabetic patients with multi-vessel disease. The trial found that ticagrelor was not non-inferior to prasugrel in this high-risk group. The findings are consistent with the ISAR-REACT 5 trial, which showed prasugrel's superiority over ticagrelor.
- The Tuxedo 2 India trial focused on a high-risk subgroup of diabetic patients with multi-vessel disease.
- Ticagrelor failed to demonstrate non-inferiority to prasugrel in the primary outcome.
- A trial-level meta-analysis combining Tuxedo 2 India and ISAR-REACT 5 data showed prasugrel's superiority in reducing ischemic events.
Background and Context: ISAR-REACT 5 Trial [0:29]
The discussion begins with the ISAR-REACT 5 trial, a pivotal study comparing prasugrel and ticagrelor in patients with acute coronary syndrome (ACS). ISAR-REACT 5 demonstrated that prasugrel was superior to ticagrelor in reducing the primary composite endpoint of death, myocardial infarction (MI), and stroke, without an increase in bleeding. These findings influenced the European Society of Cardiology (ESC) guidelines to recommend prasugrel over ticagrelor, a recommendation not adopted by the American College of Cardiology/American Heart Association (ACC/AHA). A subgroup analysis in diabetic patients from ISAR-REACT 5 showed no significant difference between the two drugs, which led to the hypothesis for the Tuxedo 2 India trial.
Rationale and Design of Tuxedo 2 India Trial [3:11]
The Tuxedo 2 India trial was designed to investigate whether ticagrelor could be non-inferior to prasugrel in diabetic patients with multi-vessel disease, a high-risk subgroup. The trial employed a non-inferiority design with a sequential test for superiority if non-inferiority was met. The primary outcome was a composite net benefit outcome including death, MI, stroke, and major bleeding, with a non-inferiority margin of 5%. The trial had a 2x2 factorial design, also comparing the Superflex stent against the Zans stent.
Eligibility Criteria and Patient Population [5:40]
The eligibility criteria for the Tuxedo 2 India trial mirrored those of the FREEDOM trial, focusing on patients with diabetes and multi-vessel coronary artery disease. The trial required patients to have two or more diseased vessels, with a cap of 15% for those with two-vessel disease, ensuring that the majority (85%) had triple-vessel disease. Key exclusion criteria included recent stroke, significant neurological deficits, advanced heart failure, and contraindications to antiplatelet therapy. The trial enrolled 1,800 patients, with 85% having triple-vessel disease and the majority having type 2 diabetes.
Co-interventions and Guideline-Directed Medical Therapy [9:56]
The trial emphasized guideline-directed medical therapy (GDMT) optimization, including glycemic control, LDL management, and blood pressure control, in addition to antiplatelet therapy. At one year, approximately 80% of patients reached their HbA1c goal of less than 7%, and 80% achieved an LDL level of less than 70 mg/dL. A significant percentage of patients also reached their blood pressure control goals, highlighting the focus on comprehensive risk factor management.
Primary Treatment Effect and Safety Estimates [11:29]
The primary outcome of the Tuxedo 2 India trial showed that ticagrelor failed to meet the pre-specified non-inferiority threshold compared to prasugrel. The risk difference for the upper confidence interval was close to 6%, with a non-inferiority p-value of 0.84. Although not statistically significant, numerical point estimates favored prasugrel for both ischemic and bleeding endpoints.
Secondary Endpoints and Consistency of Findings [13:14]
The findings were consistent across all secondary and composite endpoints, with the majority of point estimates favoring prasugrel. This consistency reinforced the primary outcome results, indicating a potential benefit of prasugrel over ticagrelor in this specific patient population.
Focus on India and Historical Context [13:53]
The focus on conducting the trial in India stems from a long-standing collaboration with local researchers. A previous trial, the original Tuxedo trial, compared Zans and Taxus stents and challenged the notion that Taxus stents were particularly effective in diabetic patients. This ongoing collaboration and the specific characteristics of the Indian patient population motivated the Tuxedo 2 India trial.
Meta-Analysis of Tuxedo 2 India and ISAR-REACT 5 [15:22]
A trial-level meta-analysis combining the Tuxedo 2 India and ISAR-REACT 5 trials demonstrated that prasugrel was superior to ticagrelor in reducing the risk of ischemic events by 28%. Although there was no statistically significant difference in bleeding endpoints, the point estimate favored prasugrel. This analysis underscores the potential benefits of prasugrel in reducing ischemic events compared to ticagrelor.
