Aspirin and heparin pretreatment in STEMI following 2023 ESC guideline update - a propensity score matched analysis from a metropolitan STEMI registry

Sascha Macherey-Meyer (Köln)1, S. Heyne (Köln)2, M. Meertens (Mainz)3, S. Braumann (Köln)2, I. Ahrens (Köln)4, F. M. Baer (Köln)5, F. Eberhardt (Köln)6, M. Horlitz (Köln)7, J.-M. Sinning (Köln)8, A. Meissner (Köln)9, B. Rosswinkel (Köln)10, S. Baldus (Köln)1, C. Adler (Köln)11, S. Lee (Köln)11

1Herzzentrum der Universität zu Köln Klinik für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland; 2Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; 3Universitätsmedizin der Johannes Gutenberg-Universität Mainz Zentrum für Kardiologie Mainz, Deutschland; 4Krankenhaus der Augustinerinnen, Akademisches Lehrkrankenhaus Klinik für Kardiologie und internistische Intensivmedizin Köln, Deutschland; 5St. Antonius Krankenhaus Medizinische Klinik & Kardio-Diabetes-Zentrum Köln Köln, Deutschland; 6Ev. Krankenhaus Köln-Kalk Kardiologie & Internistische Intensivmedizin Köln, Deutschland; 7Krankenhaus Porz am Rhein gGmbH Klinik für Kardiologie, Elektrophysiologie u. Rhythmologie Köln, Deutschland; 8St. Vinzenz-Hospital Innere Medizin III - Kardiologie Köln, Deutschland; 9Kliniken der Stadt Köln gGmbH, Krankenhaus Merheim Medizinische Klinik II Köln, Deutschland; 10Institut für Medizinische Statistik und Bioinformatik, Universität zu Köln, Köln, Deutschland; 11Universitätsklinikum Köln Klinik III für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland


Background: Thrombotic coronary occlusion is the predominant underlying pathology in ST-segment myocardial infarction (STEMI). Recent 2023 ESC guideline recommends the use of aspirin (ASA) and heparin immediately – so called pretreatment – at the time of STEMI diagnosis. But for the first time, the guideline authors emphasized the gap in the evidence of this pretreatment strategy. Especially anticoagulatory pretreatment has rarely demonstrated advantages in major cardiac events in STEMI, so far. Given the omnipresent bleeding and ischemic risk in STEMI patients further analysis on preinterventional pretreatment is needed.

Objective: This study examined the implications of preinterventional pretreatment with ASA and heparin in a metropolitan all-comer STEMI cohort: Is pretreatment required in an urban setting with streamlined treatment pathways?

Methods: The STEMI registry includes patients treated between January 2005 and December 2020. Patients were divided in completely pretreated (ASA + heparin) and remaining patients without or incomplete pretreatment (single ASA or heparin, or nothing). Propensity score matching (3:1) including multiple imputation was performed to balance the groups. Primary outcome was in-hospital mortality. Secondary outcomes were access site bleeding, acute infarct-related artery total occlusion (TIMI 0 flow), and creatinkinase (U/L). Data were analyzed using Student’s t, Chi square and Fisher’s exact test.

Results: 4631 patients including 4364 (94.2%) pretreated and 267 (5.8%) patients without or with incomplete pretreatment were eligible. In-hospital mortality was 8.8% in pretreated vs. 18.3% in the comparator group (p<0.001). Completely pretreated patients had a lower rate of acute total coronary artery occlusion (13.1 vs 20.3%, p<0.01). Access site bleeding (0.9 vs. 1.6%, p=0.307) and maximum creatinkinase level (1912 vs. 2170 U/L, mean, p=0.160) did not significantly differ between the groups. The groups were significantly imbalanced in baseline characteristics (see figure).

After propensity score matching adjusting for covariates of interest (marked by asterisk in figure) 1025 patients (3:1 ratio, 758 vs. 267) remained for further analysis. In this analysis, in-hospital mortality was 15.6% in completely pretreated vs. 18.6% in the comparator group (p<0.271). Acute total coronary occlusion (19.1 vs. 25.8%, p= 0.636) and access-site bleeding (1.2 vs 1.5%, p=0.752) did not significantly differ between the groups. Maximum creatinkinase levels were 1879 and 2157 U/L, respectively (mean, p=0.254).

Conclusion: Patients with combined pretreatment aspirin + heparin were associated with lower in-hospital mortality and less acute coronary occlusions in this registry analysis. While it did not increase access-site bleeding. But patients with complete pretreatment had more favorable baseline characteristics. Reasons for withholding pretreatment are uncertain in retrospective evaluation, but these patients were older and more often displayed hemodynamic, respiratory or electric instability. Adjustment for these covariates did result in similar outcome irrespective of pretreatment status. This challenges the causality of pretreatment on outcome, and confounding in the overall cohort can be assumed. 

Considering findings from this hypothesis-generating analysis and the prior neutral reports - especially on heparin pretreatment in STEMI - a randomized controlled trial might be warranted to close the gap in the evidence.

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