Prasugrel Outperforms Ticagrelor in Reducing Mortality and Stroke in Routine Acute Coronary Syndrome Care: JAMA

The research, conducted in routine care settings, revealed that prasugrel was linked to reduced rates of all-cause mortality, myocardial infarction (MI), or stroke compared to ticagrelor among individuals with acute coronary syndrome undergoing invasive treatment in routine care, especially in those with ST-segment elevation myocardial infarction.

In patients with ACS undergoing invasive treatment, ticagrelor, and prasugrel are guideline-recommended P2Y12 receptor inhibitors, with the ISAR-REACT5 randomized clinical trial demonstrating prasugrel's superiority. However, concerns about the generalizability of certain underpowered subgroup analyses have persisted. To address these concerns, Nils Krüger, Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany, and colleagues aimed to emulate a randomized clinical trial by evaluating the safety and effectiveness of ticagrelor versus prasugrel under routine care conditions in individuals with ACS who were planned for an invasive treatment strategy.

For this purpose, the researchers conducted a new-user cohort study using German statutory health insurance claims data from 2012 to 2021. They applied 1:1 propensity score matching to emulate the ISAR-REACT5 trial. The study included individuals aged 18 years or older with acute coronary syndrome treated with ticagrelor or prasugrel after hospital discharge, followed for one year.

The primary outcome was a composite of all-cause mortality, myocardial infarction, or stroke, with secondary outcomes including stent thrombosis and major bleeding—data analysis from May 2023 to May 2024, employing Cox regression for the overall cohort.

The study led to the following findings:

• The study analyzed 17,642 propensity score–matched individuals (mean age 63.1 years; 73.9% male), with 8,821 receiving ticagrelor and 8,821 receiving prasugrel.
• Agreement with the ISAR-REACT5 trial was observed in 11 of 12 predefined metrics.
• The primary composite endpoint (all-cause mortality, myocardial infarction, or stroke) occurred in 9.2% of the ticagrelor group and 7.5% of the prasugrel group (HR 1.24).
• Myocardial infarction (HR 1.20) and stroke (HR 1.33) were significantly more frequent in the ticagrelor group.
• No significant differences were observed in all-cause mortality (HR 1.27), stent thrombosis (HR 1.11), or major bleeding (HR 1.12).
• Subgroup analysis showed fewer primary endpoint events with prasugrel in ST-segment elevation MI cases (6.8% versus 9.3%).

The authors of this cohort study analyzed 17,642 individuals discharged after invasive treatment for acute coronary syndrome (ACS). They found that prasugrel was associated with significantly lower rates of all-cause mortality, myocardial infarction, or stroke compared to ticagrelor, without an increased risk of bleeding. These results align with the superior effectiveness of prasugrel observed in prior randomized clinical trials like ISAR-REACT5.

The study also provided insights into ACS subtypes, showing that prasugrel yielded better outcomes in patients with ST-segment elevation myocardial infarction (STEMI). At the same time, there were no significant differences in patients with non-STEMI or unstable angina.

"These findings further support guideline recommendations favoring prasugrel over ticagrelor for patients with acute myocardial infarction undergoing invasive treatment," the researchers concluded.

Reference:

Krüger N, Krefting J, Kessler T, et al. Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care. JAMA Netw Open. 2024;7(12):e2448389. doi:10.1001/jamanetworkopen.2024.48389