Love Emilsson - Institutionen för kliniska vetenskaper, Lund

Title: Contemporary Care in Acute Coronary Syndrome: effectiveness, safety, and use

Main supervisor: Sasha Koul

Reviewers: Andreas Edfeldt, Henrik Wagner, and Helle Søholm

Abstract

Background

Antithrombotic therapy and temporary mechanical circulatory support (tMCS) constitute treatment strategies in the management of acute coronary syndrome (ACS).

Research questions

To describe and explore outcomes associated with treatment of ACS, with focus on (i) heparin pretreatment in ST-elevation myocardial infarction (STEMI), (ii) cangrelor in myocardial infarction (MI) complicated by cardiogenic shock or cardiac arrest, (iii) ticagrelor versus clopidogrel combined with direct oral anticoagulants (DOAC), and (iv) tMCS. 

Preliminary results

In this thesis, data from nationwide quality registers within cardiology were linked with the National Patient Register and the Swedish Prescribed Drug Register. In three non-randomised controlled studies, effectiveness and safety outcomes were investigated using Poisson regression and Cox regression, controlling for confounders using adjusted analyses, propensity score (PS) matching and inverse probability treatment weighting. In the fourth study, descriptive statistics will be used to explore the use of tMCS.  Analysing 41,631 patients with STEMI, the adjusted  risk ratios (RRs) of heparin pretreatment versus no heparin pretreatment were 0.89 (95% confidence interval: 0.87–0.90) for coronary artery occlusion, 0.87 (0.77–0.99) for mortality within 30 days, and 1.01 (0.86–1.18) for major in-hospital bleeding. Investigating 994 PS-matched patients with MI and cardiogenic shock, the RRs for cangrelor versus no cangrelor were 0.81 (0.70–0.94) for mortality within 30 days and 1.60 (0.93–2.76) for major in-hospital bleeding. In 1,138 PS-matched patients with MI complicated by cardiac arrest, the RRs were 0.97 (0.83–1.13) for mortality within 30 days and 2.26 (1.25–4.11) for major in-hospital bleeding. Evaluating the addition of ticagrelor to DOAC, compared with clopidogrel, in 3,708 ACS patients, the adjusted hazard ratios were 1.02 (0.84–1.23) for major adverse cardiovascular events within one year and 1.53 (1.06–2.22) for bleeding within one year. Analyses of tMCS use are ongoing.

Significance

Across three controlled nationwide register studies, clinically relevant patterns of associations between treatment strategies and patient outcomes were found. Pretreatment with heparin in STEMI, and cangrelor in MI and cardiogenic shock, were associated with clinical benefit, including a lower 30-day mortality. Cangrelor in MI complicated by cardiac arrest, and addition of ticagrelor versus clopidogrel to DOAC in ACS, were associated with harm, with an increased risk of bleeding and without clinical benefits.

Published studies

1. Emilsson OL, Bergman S, Mohammad MA, Olivecrona GK, Götberg M, Erlinge D, Koul S. Pretreatment with heparin in patients with ST-segment elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). EuroIntervention. 2022 Oct 21;18(9):709-718. doi: 10.4244/EIJ-D-22-00432. PMID: 36036797; PMCID: PMC10241276.
2. Emilsson OL, Koul S. Reply: Pretreatment with unfractionated heparin in patients undergoing primary PCI: a standard of treatment together with DAPT? EuroIntervention. 2023 Apr 24;18(17):1473-1474. doi: 10.4244/EIJ-D-22-00867. PMID: 37092267; PMCID: PMC10111130.
3. Emilsson OL, Mohammad MA, Grimfjärd P, Persson J, Santos-Pardo I, Erlinge D, Koul S. Cangrelor During Percutaneous Coronary Intervention in Patients With Cardiogenic Shock or Cardiac Arrest. JACC Cardiovasc Interv. 2025 Apr 14;18(7):853-862.doi: 10.1016/j.jcin.2025.01.451. PMID: 40240083.
4. Emilsson OL, Koul S. Reply: Critical Unaddressed Limitations in the Cangrelor Study for High-Risk PCI Patients. JACC Cardiovasc Interv. 2025 Aug 11;18(15):1953. doi: 10.1016/j.jcin.2025.06.027. PMID: 40803766.