Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2024 Dec 2;7(12):e2448389.
doi: 10.1001/jamanetworkopen.2024.48389.

Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care

Nils Krüger  1   2 , Johannes Krefting  1   2 , Thorsten Kessler  1   2 , Raphael Schmieder  1   2 , Fabian Starnecker  1   2 , Alexander Dutsch  1   2 , Christian Graesser  1   2 , Ulrike Meyer-Lindemann  1   2 , Theresa Storz  1 , Irina Pugach  1 , Christian Frieß  1 , Zhifen Chen  1   2 , Dario Bongiovanni  3 , Iulian Manea  4 , Tobias Dreischulte  5 , Frank Offenborn  6 , Peter Krase  6 , Hendrik B Sager  1   2 , Jens Wiebe  1   2 , Sebastian Kufner  1 , Erion Xhepa  1 , Michael Joner  1   2 , Teresa Trenkwalder  1   2 , Ulrich Gueldener  1 , Adnan Kastrati  1   2 , Salvatore Cassese  1 , Heribert Schunkert  1   2 , Moritz von Scheidt  1   2 ; DigiMed Bayern Consortium
Collaborators, Affiliations
Comparative Study

Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care

Nils Krüger et al. JAMA Netw Open. .

Erratum in

Abstract

Importance: In patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. The ISAR-REACT5 randomized clinical trial demonstrated superiority for prasugrel, although concerns were raised about the generalizability of some underpowered subgroup analyses.

Objectives: To emulate a randomized clinical trial evaluating the safety and effectiveness of ticagrelor vs prasugrel under the conditions of routine care in individuals with ACS planned to undergo an invasive treatment strategy.

Design, setting, and participants: This new-user cohort study included secondary data from a German statutory health insurance claims database between January 2012 and December 2021, using 1:1 propensity score nearest-neighbor matching to emulate ISAR-REACT5. Individuals with ACS receiving either ticagrelor or prasugrel treatment after hospital discharge were followed up for 1 year. Eligibility criteria closely emulated those of ISAR-REACT5 and included age of 18 years or older and cardiovascular risk factors. Data were analyzed from May 2023 to May 2024.

Exposure: Outpatient prescription of ticagrelor or prasugrel.

Main outcomes and measures: The primary end point was the composite of all-cause mortality, myocardial infarction (MI), or stroke within 1 year of outpatient treatment initiation. Secondary end points included individual components of the primary end point and stent thrombosis. The safety end point was major bleeding. A Cox proportional hazards regression model was fitted to the overall cohort.

Results: Of 17 642 propensity score-matched individuals (mean [SD] age, 63.1 [10.9] years; 73.9% male), 8821 received ticagrelor and 8821 received prasugrel. Agreement was met in 11 of 12 predefined agreement metrics when comparing the results with ISAR-REACT5. The primary composite end point of all-cause mortality, MI, or stroke occurred in 815 individuals (9.2%) receiving ticagrelor and 663 (7.5%) receiving prasugrel (hazard ratio [HR], 1.24; 95% CI, 1.12-1.37). Myocardial infarction (HR, 1.20; 95% CI, 1.06-1.36) and stroke (HR, 1.33; 95% CI, 1.02-1.74) each occurred significantly more often in the ticagrelor group. Analysis of all-cause mortality (HR, 1.27; 95% CI, 0.99-1.64), stent thrombosis (HR, 1.11; 95% CI, 0.89-1.30), and major bleeding (HR, 1.12; 95% CI, 0.96-1.32) revealed no significant differences between treatment groups. Subgroup analysis showed that prasugrel was associated with the primary composite end point in fewer individuals with ST-segment elevation MI (338 of 4941 [6.8%] vs 451 of 4852 [9.3%]).

Conclusions and relevance: This cohort study found that prasugrel was associated with lower rates of all-cause mortality, MI, or stroke compared with ticagrelor in individuals with ACS undergoing an invasive treatment strategy in routine care, particularly in individuals with ST-segment elevation MI. The findings suggest that carefully designed database studies can complement and extend findings from randomized clinical trials, informing guidelines and clinical decision-making.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Krüger reported receiving grants from the German Heart Foundation and the Deutsches Zentrum für Herz-Kreislauf-Forschung outside the submitted work. Dr Kessler reported receiving personal fees from Abbott, Translumina, Bristol Myers Squibb, and AstraZeneca and grants from the German Research Foundation, European Research Council, and Corona Foundation outside the submitted work and having patents PCT/EP2021/053116 and US 2023/137816 pending. Dr Graesser reported receiving grants from the Clinician Scientist Programme outside the submitted work. Dr Sager reported receiving research grants from the German Research Foundation, Else Kröner-Fresenius-Stiftung, and the European Research Council outside the submitted work. Dr Wiebe reported receiving speaker fees from AstraZeneca and Translumina and an institutional research grant and speaker fees from Abbott outside the submitted work. Dr Kufner reported receiving personal fees from AstraZeneca, BMS, Boehringer Ingelheim, Bentley, and Translumina outside the submitted work. Dr Joner reported receiving personal fees from Abbott, AlchiMedics, AstraZeneca, Biotronik, Boston Scientific, Cardiac Dimensions, Edwards, Medtronic, ReCor, Shockwave, TRiCares, and Veryan and grants from Boston Scientific outside the submitted work. Dr Schunkert reported receiving honoraria from Amarin, Amgen, AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Medtronic, MSD Sharp & Dohme, Novartis, Pfizer, Sanofi Aventis, Servier, and Synlab outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Overview of Screening, Eligibility Assessment, and Propensity Score Matching (PSM)
Specific International Statistical Classification of Diseases, Tenth Revision, German Modification (ICD-10-GM) codes are provided for exclusion criteria. ACS indicates acute coronary syndrome.
Figure 2.
Figure 2.. Cumulative Incidence of the Primary End Point and Safety End Point at 1 Year
The Kaplan-Meier curves show the cumulative incidence of the primary composite end point (all-cause mortality, myocardial infarction [MI], or stroke) and of the safety outcome, major bleeding. Aalen-Johansen estimates are provided for bleeding considering competing risk of death.
Figure 3.
Figure 3.. Cumulative Incidence of Secondary End Points at 1 Year
The Kaplan-Meier curves show the cumulative incidence of the secondary end points—individual components of the primary end point (all-cause mortality, myocardial infarction [MI], and stroke) as well as stent thrombosis. Aalen-Johansen estimates are provided for MI, stroke, and stent thrombosis considering competing risk of death.
See this image and copyright information in PMC

References

    1. Schüpke S, Neumann FJ, Menichelli M, et al. ; ISAR-REACT 5 Trial Investigators . Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019;381(16):1524-1534. doi:10.1056/NEJMoa1908973 - DOI - PubMed
    1. Motovska Z, Hlinomaz O, Kala P, et al. ; PRAGUE-18 Study Group . 1-Year outcomes of patients undergoing primary angioplasty for myocardial infarction treated with prasugrel versus ticagrelor. J Am Coll Cardiol. 2018;71(4):371-381. doi:10.1016/j.jacc.2017.11.008 - DOI - PubMed
    1. Motovska Z, Hlinomaz O, Miklik R, et al. ; PRAGUE-18 Study Group . Prasugrel versus ticagrelor in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: multicenter randomized PRAGUE-18 study. Circulation. 2016;134(21):1603-1612. doi:10.1161/CIRCULATIONAHA.116.024823 - DOI - PubMed
    1. Byrne RA, Rossello X, Coughlan JJ, et al. ; ESC Scientific Document Group . 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191 - DOI - PubMed
    1. Levine GN, Bates ER, Bittl JA, et al. . 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation. 2016;134(10):e123-e155. doi:10.1161/CIR.0000000000000404 - DOI - PubMed

Publication types