PLATO Subanalysis: Ticagrelor Safe, Effective in Primary PCI
New findings from the PLATO trial indicate that ticagrelor is comparable to clopidogrel for most safety and efficacy endpoints in STEMI patients who undergo primary PCI within 12 hours of hospital admission, according to a presentation by Philippe Gabriel Steg, MD, of Groupe Hospitalier Bichat – Claude Bernard, Paris, France.
Steg presented data on the subgroup of 7,544 patients with persistent ST-elevation acute coronary syndromes (STE-ACS) or left bundle branch block on ECG at entry. Among them, 4,949 underwent an invasive treatment and primary PCI within 12 hours of admission.
The PLATO trial was a randomized, double blind-study that compared ticagrelor (Brilinta, AstraZeneca) with clopidogrel in 18,624 patients with ACS, with or without ST-segment elevation. Overall results from the trial, published in the New England Journal of Medicine in 2009, showed that ticagrelor reduced not only the composite of CV death, MI or stroke (primary endpoint) but also 12-month rates of stent thrombosis.
Primary PCI subgroup results
Outcomes in the primary PCI subset appear to be consistent with those of the larger study population, reported Steg. Yet the decrease in the primary endpoint did not reach statistical significance (see Figure). In addition, the safety outcome of major bleeding was similar between ticagrelor (6.7%) and clopidogrel (6.8%; HR 0.97; 95% CI 0.77-1.22; P=.79).
Importantly, there was no interaction for the primary efficacy or safety endpoints between open-label use of clopidogrel before randomization and the treatment effect of ticagrelor vs. clopidogrel. Similarly, there was no interaction between glycoprotein IIb/IIIa inhibitor use before randomization and treatment effect.
Steg noted that one explanation for the diminished benefit of ticagrelor is the smaller patient population of the primary PCI subgroup compared with that of the larger trial. “But of course, we all know that the P value in a subset is not what defines the effect in that subset,” Steg said. “What counts when we’re analyzing a subset is the interaction you get.”
To make his point, Steg demonstrated that the same waning treatment effect can be observed in primary PCI patients who were assigned prasugrel (Effient, Daiichi Sankyo/Eli Lilly and Company) in the TRITON trial, suggesting no interaction between STEMI subset and treatment effect.
Primary PCI patients in PLATO tended to be younger, have fewer comorbidities and were less likely to have a prior medical history than the overall STE-ACS subgroup and the larger study population. They also were more likely to be assigned a treatment earlier after symptom onset and receive more intensive antithrombotic treatment.
- Steg reports conflicts of interest with multiple device and pharmaceutical companies.
- The PLATO study was funded by AstraZeneca.