DAPT in ACS: more evidence on choice of P2Y12 inhibitor

Ticagrelor compared with clopidogrel as part of dual-antiplatelet therapy (DAPT) is not associated with a significant difference in the risk of net adverse clinical events (NACE) in patients with acute coronary syndrome treated with PCI, research shows.

A retrospective study of 31,290 propensity-matched pairs from two US databases and one South Korean database, found the overall incidence of NACE at 12 months was 15.1% in the ticagrelor group and 14.6% in the clopidogrel group.

NACE were defined as a composite outcome of ischaemic events (recurrent MI, revascularisation, or ischaemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding).

Similarly in secondary outcomes, there was no difference between the two groups in all-cause mortality (2.0% v 2.1%), ischaemic events (13.5% v 13.4%), ischaemic stroke (0.7% v 0.8%), recurrent AMI (8.1% v 8.2%) or revascularisation (4.3% v 4.3%).

However ticagrelor was associated with a statistically significant higher risk of haemorrhagic events (2.1% v 1.6%), dyspnoea (27.3% v 22.6%), haemorrhagic stroke (0.3% v 0.2%), and GI bleeding (1.9% v 1.4%).

“The risk of cardiovascular-related mortality (1.4% for ticagrelor vs 1.5% for clopidogrel; summary HR, 0.98 [95% CI, 0.76-1.26]; P = .86) and MACE (7.3% for ticagrelor vs 7.2% for clopidogrel; summary HR, 1.05 [95% CI, 0.90- 1.22]; P = .51) did not significantly differ between groups,” the study said.

The study, published in JAMA, said their findings were consistent with other recent studies.

However, they said American and European guidelines recommend ticagrelor over clopidogrel largely due to evidence from the 2011 PLATO trial.

The authors said an explanation for the different findings was that most patients in PLATO received bare metal stents or first generation drug-eluting stents.

“The recent clinical trials, which reported comparable thrombotic event rates between the ticagrelor and clopidogrel groups, mostly used second-generation drug-eluting stents, which might have reduced the need for a stronger P2Y12 inhibitor.”

An accompanying editorial in JAMA said the results “challenge the conventional wisdom promoted in clinical guidelines and communicated by thought leaders and in the media that ticagrelor is more effective than clopidogrel in DAPT.”

The editorial noted that ticagrelor had a more favourable pharmacodynamic profile than clopidogrel.

“However, compared with clopidogrel and prasugrel, ticagrelor may not demonstrate greater clinical benefit because of adverse effects (dyspnea), inconvenience (twice-daily dosing), or higher cost (clopidogrel and prasugrel are generics), which may decrease medication adherence.”

“The pragmatic clinical recommendation, yet to be proven in randomised trials, may be to prescribe ticagrelor (or prasugrel because it was more effective than ticagrelor in one randomised trial) for patients with ACS, if the patient tolerates and can afford this medication, and to consider deescalating to clopidogrel at 1 month after the greatest ischaemic risk period has passed to decrease subsequent bleeding risk and cost. At 12 months, DAPT can be transitioned to low-risk aspirin monotherapy for secondary prevention.”

CSANZ guidelines recommend DAPT with either ticagrelor or clopidogrel for up to 12 months in patients with ACS regardless of whether revascularisation was performed.

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