Pre-hospital vs Cath-Lab heparin in STEMI: a reappraisal based on the HELP-PCI trial findings

This commentary refers to ‘Heparin administration at first medical contact vs. immediately before primary percutaneous coronary intervention: the HELP-PCI trial’, by J. Chen et al., https://doi.org/10.1093/eurheartj/ehaf481 and the discussion piece ‘Pre-hospital Heparin Improves Coronary Flow in STEMI: Insights and Implications from the HELP-PCI Trial’, by M. Wang and J. Chen, https://doi.org/10.1093/eurheartj/ehaf850. Dr Chen et al.1 conducted a multicentre, open-label, randomized controlled trial (RCT) in China.1 They reported that pre-treatment with a loading dose of unfractionated heparin (UFH) at the FMC for patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) was associated with improved spontaneous reperfusion of the infarct-related artery, without increasing the risk of major bleeding. However, we think there are several methodological and interpretative limitations that warrant careful consideration before this strategy is adopted into routine practice. Firstly, the study was open-label, which introduces potential bias in outcome assessment. Patients’ and clinicians’ knowledge of treatment allocation could influence decisions regarding procedural techniques, adjunct therapies, or endpoint adjudication. For example, interventional cardiologists may adopt a more aggressive approach to thrombus management if they are aware of the pre-treatment status, which could skew the results. Secondly, the sample size was calculated based on TFG-3 differences rather than clinical endpoints. Given the low event rates (e.g. 5.5% vs 6.7% major adverse cardiac and cerebrovascular events (MACCE) at 1 year), the study lacked the power to detect meaningful differences in hard outcomes. A post hoc analysis suggested an early reduction in MACCE (within 30 days), but this was likely underpowered and exploratory, increasing the risk of type II error.2 Thirdly, in the Cath Lab group, UFH timing and dosing were left to the discretion of the operator, introducing variability. Standardization (e.g. fixed time/dose) would have reduced confounding factors. Additionally, 11% of the FMC group crossed over to the Cath Lab UFH group, which may have diluted the treatment effects. Fourthly, myocardial reperfusion was assessed using ST-segment resolution and the TIMI myocardial perfusion grade, but advanced imaging techniques such as cardiac MRI were absent. The long-term prognostic significance of microvascular obstruction and infarct size was not evaluated. Fifthly, landmark analyses (e.g. 30-day MACCE) were conducted post hoc, which increases the risk of false positives.3 Subgroup analyses (e.g. glycoprotein IIb/IIIa inhibitor use) lacked multiplicity adjustment, which undermined their reliability. All authors declare no disclosure of interest for this contribution.