Intravenous cangrelor fell short of non-inferiority in heart-attack shock

A heart attack serious enough to tip the circulation into cardiogenic shock — where the heart can no longer pump enough blood to keep organs supplied — is among the deadliest events in cardiology. It also creates a quiet pharmacological problem. The clot-preventing tablets given during an emergency stenting procedure have to be swallowed and absorbed, and in a patient in shock the gut may barely be working. A trial published in The Lancet on 7 November tested whether bypassing the gut entirely would help [s1].

The question

Patients having a primary percutaneous coronary intervention — emergency stenting — are given a P2Y12 inhibitor, a drug that stops platelets clumping into fresh clots. The standard option is an oral drug such as ticagrelor, sometimes crushed to speed absorption. But in shock, absorption is slow and unreliable, which may leave platelets inadequately blocked at the worst possible moment.

Cangrelor is different: it is given intravenously, acts within minutes, and wears off quickly once stopped. DAPT-SHOCK-AMI, registered as NCT03551964, asked whether intravenous cangrelor was non-inferior to crushed ticagrelor for short-term outcomes, and whether it produced faster, more consistent platelet blockade, in patients whose heart attack was complicated by cardiogenic shock [s1][s2].

How the trial was built

This was a double-blind, randomised trial run at 29 hospitals across five European countries — the Czech Republic, France, Germany, Poland and Slovakia [s1]. Patients over 18 with a heart attack complicated by cardiogenic shock were assigned 1:1 to cangrelor — a 30 microgram/kg bolus followed by an infusion of 4 micrograms/kg per minute for at least two hours — or a 180 mg loading dose of crushed ticagrelor [s1].

The trial carried two primary endpoints. The laboratory one was a platelet reactivity index below 50% — effective platelet suppression — at the end of the stenting procedure. The clinical one was a composite of death, myocardial infarction or ischaemic stroke at 30 days, tested for non-inferiority against a prespecified margin of one percentage point [s1].

Between August 2018 and January 2024, 605 patients were randomised, 298 to cangrelor and 307 to ticagrelor; 137 (23%) were female, and no surviving patient was lost to one-year follow-up [s1].

What it found

On the laboratory measure, cangrelor was decisively more reliable. Among patients in whom it was assessed, effective platelet suppression was achieved in 56 of 56 (100%) on cangrelor versus 15 of 68 (22%) on crushed ticagrelor (p<0.0001) [s1]. In other words, nearly four in five patients given the crushed tablet did not reach adequate platelet blockade by the end of the procedure.

That pharmacological advantage did not translate into a proven clinical one. The 30-day composite of death, myocardial infarction or ischaemic stroke occurred in 112 of 298 patients (38%) on cangrelor and 126 of 307 (41%) on ticagrelor [s1]. The numerical difference favoured cangrelor, but non-inferiority was not demonstrated: the difference was −4 percentage points (90% CI −10 to 3), and the formal non-inferiority test returned p=0.13 [s1]. The confidence interval was simply too wide to rule out that cangrelor could be meaningfully worse by the trial's own standard.

Bleeding, the main safety concern with stronger platelet blockade, was similar: major bleeding at 30 days occurred in 19 patients (6%) on cangrelor and 16 (5%) on ticagrelor [s1].

What is, and is not, established

By the authors' account this is the first randomised trial to compare P2Y12 inhibitor strategies specifically in patients with a heart attack complicated by cardiogenic shock — a group usually excluded from antiplatelet trials [s1]. It establishes that intravenous cangrelor achieves effective platelet suppression far more consistently than a crushed oral tablet in these patients [s1].

What it does not establish is that this consistency improves survival or reduces heart attacks and strokes. The clinical endpoint was numerically better with cangrelor but failed its non-inferiority test, so the trial cannot claim the two strategies are equivalent, let alone that one is superior [s1]. The high event rate — roughly four in ten patients met the composite by 30 days — is a reminder of how lethal this condition remains regardless of which antiplatelet is used [s1]. Five-year follow-up is ongoing [s1].

This article describes research and is not medical advice. Decisions about antiplatelet treatment in an acute heart attack are made by the treating cardiology team.