Intravenous cangrelor provides rapid platelet inhibition in cardiogenic shock

Compared with crushed ticagrelor, intravenous cangrelor provided immediate, effective platelet inhibition, with no increase in major bleeding and lower mortality rates in patients with acute myocardial infarction and cardiogenic shock, according to late-breaking research presented in a Hot Line session today at ESC Congress 2025.

Cardiogenic shock is a life-threatening condition in which the heart cannot pump enough blood to meet the body's needs. It is present in around 4.6% of patients admitted to hospital for acute myocardial infarction (MI) and is associated with in-hospital mortality rates of 44%. Reperfusion using primary percutaneous coronary intervention (PCI) remains the only universal therapeutic approach that improves prognosis.

Achieving early and effective platelet inhibition is vital for reperfusion at the microcirculatory level in patients with MI complicated with cardiogenic shock. However, major randomized trials on the efficacy and safety of antiplatelet drugs have not included patients with cardiogenic shock. Currently, oral crushed ticagrelor tablets are given; however, the parenteral, direct-acting, reversible P2Y12 inhibitor, cangrelor, may address issues that occur during cardiogenic shock, including poor absorption and impaired liver metabolism. The DAPT-SHOCK-AMI trial - comparing IV cangrelor with crushed ticagrelor - is the first-ever randomized study evaluating the efficacy and safety of antiplatelet agents in this setting."

Principal Co-Investigator, Professor Zuzana Motovska from the Charles University and University Hospital Kralovske Vinohrady, Prague, Czechia

This double-blind, placebo-controlled randomized trial was conducted at 29 sites in Czechia, France, Germany, Poland and Slovakia. Key inclusion criteria were acute MI with an indication for emergency primary PCI and cardiogenic shock that fulfilled at least two of: a) systolic blood pressure <90 mmHg in the absence of hypovolaemia, b) need for vasopressor and/or inotropic therapy and c) signs of organ hypoperfusion. Patients were randomized 1:1 to receive IV cangrelor (IV bolus of 30 μg/kg followed by a continuous infusion at 4 μg/kg) or oral ticagrelor (crushed tablets at a 180-mg loading dose and then a maintenance dose of 90 mg twice daily). In the cangrelor group, 30 minutes before the end of the cangrelor infusion, 180 mg of ticagrelor (crushed tablets) was administered, followed by a maintenance dose of 90 mg twice daily. Cangrelor-placebo and ticagrelor-placebo were administered in the same form as their active counterparts. The study medication was administered to all enrolled patients on top of concomitant aspirin. In total, 605 patients were randomized. The mean age was 65 years and 22.6% were women.

The primary laboratory endpoint (defined as platelet reactivity index <50% at the end of primary PCI) was achieved in 100% of patients with cangrelor and in 22.1% with ticagrelor (p for superiority<0.0001).

At 30 days, the primary clinical endpoint was not met: 37.6% of patients in the cangrelor group and 41.0% of patients in the ticagrelor group experienced all-cause death, MI or stroke (difference −3.5%, 95% confidence interval [CI] −11.2% to 4.3%; p for noninferiority=0.13).

The incidence of all-cause mortality at 12 months was 43.6% in the cangrelor group and 49.2% in the ticagrelor group (difference: −5.6%; 95% CI −13.5% to 2.4%), while the incidence of cardiovascular mortality was 26.8% and 33.2%, respectively ( −6.4%; 95% CI −13.7% to 0.9%).

The incidence of major bleeding at 30 days was 6.4% in the cangrelor group and 5.2% in the ticagrelor group (p=0.53).

Improvements were noted in primary PCI outcomes, periprocedural complications, early reinfarction and stent thrombosis rates with cangrelor compared with ticagrelor.

Principal Co-Investigator, Professor Deepak Bhatt from the Icahn School of Medicine at Mount Sinai, New York, USA, concluded: "Compared with crushed ticagrelor, IV cangrelor provided immediate, effective platelet inhibition and improved several secondary and exploratory clinical outcomes without increasing major bleeding. If verified in larger trials, IV cangrelor could represent a major advancement in the treatment of cardiogenic shock."