Pretreatment with parenteral anticoagulation in patients with ST-segment elevation myocardial infarction: a systematic review and meta-analysis

Abstract Background and Aim According to ESC guidelines, parenteral anticoagulation is recommended for all patients presenting with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PPCI). However, no specific recommendations are made regarding the timing of administration. In fact, whether upstream anticoagulation improves clinical outcomes in STEMI patients is not well established. We conducted a systematic review and meta-analysis of current evidence on parenteral anticoagulation timing for patients presenting with STEMI. Methods We performed a systematic search of electronic databases (PubMed, CENTRAL and Scopus) until December 2022. Studies were considered eligible if they a) compared upstream anticoagulation with administration at the catheterization lab; and b) enrolled patients with STEMI undergoing PPCI. Studies comparing different anticoagulants were excluded from the analysis. Random-effects meta-analyses were performed. Efficacy outcomes included TIMI flow-grade pre- and post-PPCI, in-hospital cardiogenic shock (CS) and 30-day all-cause mortality. Safety outcome was defined as major in-hospital bleeding events. Results Overall, 9 studies were included (all non-randomized), with a total of 69,571 patients (30,693 in the pretreatment arm). In all but one, anticoagulation strategy was exclusively based on unfractionated heparin. Pretreatment was associated with a significant reduction in the incidence of 30-day all-cause mortality (OR 0.61; 95% CI 0.47-0.80; p<0.001) and in-hospital CS (OR 0.69; 95% CI 0.59-0.81; p<0.001). Upstream anticoagulation was also associated with a significant increase of spontaneous reperfusion of the culprit artery before PPCI (pre-PPCI TIMI > 0: OR 1.47; 95% CI 1.35-1.60; p<0.001) and TIMI flow ≥ 2 after coronary intervention (OR 1.28; 95% CI 1.05-1.56; p=0.016). Regarding safety outcomes, pretreatment was not associated with an increase of in-hospital major bleeding (OR 1.01; 95% CI 0.70-1.44; p=0.970). Multiple sensitivity analyses, including propensity-matched populations, showed consistent results. Conclusions Upstream anticoagulation was associated with a significant lower risk of 30-day all-cause mortality, incidence of in-hospital cardiogenic shock and improved reperfusion of culprit artery. These benefits were not accompanied by an increased risk of major bleeding, suggesting an overall clinical benefit of early anticoagulation in patients presenting with STEMI. These results require confirmation in a randomized clinical trial.