Anti-Platelet Therapy with Cangrelor in Cardiogenic Shock Patients: A Systematic Review and Single-Arm Meta-Analysis

Abstract

Background and Objectives: Percutaneous coronary intervention (PCI) is a proven therapy for acute myocardial infarction (AMI) cardiogenic shock (CS). Dual anti-platelet therapy (i.e., aspirin plus an oral P2Y12 inhibitor) is recommended in patients treated with PCI. However, CS patients present severe hemodynamic instability, deranged hemostatic balance, and the need for invasive mechanical circulatory support (MCS) alongside invasive procedures, resulting in an increased risk of both bleeding and thrombotic complications, leaving uncertainty about the best anti-thrombotic treatment. Recently, the parenteral short-acting P2Y12 inhibitor has been increasingly used in the acute cardiac care setting, mainly in light of its favourable pharmacokinetic profile and organ-independent metabolism. Materials and Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review and single-arm meta-analysis of the safety and efficacy outcomes (i.e., rates of major bleeding, occurrence of stent/any thrombosis, and hospital survival) of all existing original studies reporting on the intravenous administration of cangrelor in AMI-CS patients. Results: Ten studies (678 patients with CS) published between 2017 and 2023 were included in the present review: nine were observational and one had a randomized design. Percutaneous revascularization was performed in >80% of patients across the studies. Moreover, 26% of patients were treated with temporary MCS, and in all studies, concomitant systemic anticoagulation was performed. Cangrelor was administered intravenously at the dosage of 4 mcg/kg/min in 57% of patients, 0.75 mcg/kg/min in 37% of patients, and <0.75 mcg/kg/min in 6%. The pooled rate of major bleeding was 17% (11-23%, confidence interval [CI]), and the pooled rate of stent thrombosis and any thrombosis were 1% (0.3-2.3% CI) and 3% (0.4-7% CI), respectively. Pooled hospital survival was 66% (59-73% CI). Conclusions: Cangrelor administration in AMI-CS patients was feasible and safe with a low rate of thromboembolic complications. Haemorrhagic complications were more frequent than thrombotic events. Nevertheless, to date, the optimal dosage of cangrelor in this clinical context still remains not universally recognized.

Keywords: VA-ECMO; acute myocardial infarction; cangrelor; cardiogenic shock; mechanical circulatory support; percutaneous coronary intervention.

Figure 1

Visual abstract presenting main article structure, objective, research methodology, and results. AMI-CS: acute myocardial infarction–cardiogenic shock; tMCS: temporary mechanical circulatory support.

Figure 2

Flowchart of the studies selection and identification process.

Figure 3

Dose of cangrelor in n = 281 patients from included studies (n = 10) (A). Therapeutic regimen of cangrelor in n = 120 patients from included studies (n = 10) (B). BRIDGE: The Bridging Antiplatelet Therapy with Cangrelor in Patients Undergoing Cardiac Surgery Trial; CHAMPION: Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition Trial; DAPT: dual antiplatelet therapy; ASA: aspirin; SAPT: single anti-platelet therapy.

Figure 4

Type and strategy (single- or multi-device) of mechanical circulatory support (MCS) in n = 173 patients from included studies (n = 10). VA-ECMO: venoarterial extracorporeal membrane oxygenation; IABP: intra-aortic balloon pump.

Figure 5

The effect of cangrelor on the rate of major bleeding (A) [9,21,24,25,26,27,28,29,30,31], hospital survival (B) [21,25,26,28,29,30,31], thrombosis (C) [9,21,24,25,26,27,28,29,30], and any thrombotic event (D) [9,21,24,25,26,27,29,30].