Cangrelor in critically ill patients with cardiogenic shock or post-cardiac arrest undergoing percutaneous coronary intervention: a systematic review and meta-analysis

Background: Evidence for cangrelor in critically ill patients remains extremely limited, despite heightened thrombotic risk from delayed oral P2Y12 inhibitor effects post- percutaneous coronary intervention (PCI). We aim to assess intravenous (IV) cangrelor’s efficacy and safety in patients with cardiogenic shock (CS) or post-cardiac arrest (CA) undergoing PCI. Methods: This systematic review and meta-analysis (PROSPERO number: CRD420251126926) searched PubMed, Embase, and the Cochrane library to identify studies comparing adjunctive cangrelor with oral P2Y12 inhibitor during PCI in patients with CS or CA, published up until August 31, 2025. Efficacy endpoints included all-cause mortality, cardiovascular (CV) mortality, stent thrombosis, myocardial infarction (MI), stroke, and TIMI 3 flow achievement; safety endpoints were major and minor bleeding episodes. Results: A total of 12 studies including 4,537 patients were identified. Compared with the conventional treatment, adjunctive cangrelor reduced all-cause mortality overall (RR, 0.90; 95% CI, 0.82–0.98); the effect was significant in CS (RR, 0.86; 95% CI, 0.78–0.96) but not in CA (RR, 0.94; 95% CI, 0.74–1.18). No significant differences were observed in CV mortality (RR, 0.96; 95% CI, 0.76–1.22), stent thrombosis (RR, 0.72; 95% CI, 0.34–1.53), MI (RR, 0.83; 95% CI; 0.44–1.57), or stroke (RR, 1.83; 95% CI, 0.89–3.74). In addition, cangrelor was associated with higher rates of post-PCI TIMI 3 flow (RR, 1.14; 95% CI, 1.01–1.29). Major bleeding was not significantly increased overall (RR, 1.37; 95% CI, 0.95–1.97), but in controlled studies the risk was relatively increased (RR, 1.50; 95% CI, 1.10–2.05). Subgroup analyses of patients with CS supported by mechanical circulatory support, out-of-hospital CA, and CA managed with targeted temperature management showed no significant differences in clinical outcomes across all endpoints. Conclusions: IV cangrelor was associated with reduced mortality following PCI in hemodynamically unstable patients, with the most pronounced benefit observed in those with CS, alongside improved coronary flow. These findings support its role as a valuable alternative when oral P2Y12 inhibitor administration is not feasible, pending confirmation of overall clinical benefit in large-scale randomized trials.