Long-Term Ticagrelor for Secondary Prevention: Insights from PEGASUS-TIMI 54

Trial Reference
Furtado RHM, Nicolau JC, Magnani G, et al. Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54Eur Heart J. 2020;41(17):1625-1632. doi:10.1093/eurheartj/ehz821
Expert Comment
Pablo Avanzas, MD, PhD, FESC
Professor of Medicine, University of Oviedo, Oviedo, Spain

Background

PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup.

Comment

This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1–3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15–1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68–0.99) and with prior stenting (HR 0.85, 95% CI 0.75–0.96; P for interaction = 0.76).

In this subgroup analysis, the risks of MACE, CV and all-cause death were higher in patients with no history of coronary stenting, even after adjustments. These higher risks are likely multifactorial including coronary anatomy and access to PCI. Additionally, patients without prior stenting were more likely to be older and to have more comorbidities. Those factors may prompt clinicians to consider whether the risk faced by this group is modifiable by intensive antiplatelet therapy. The present analysis shows that this group derives a robust antithrombotic benefit from prolonged DAPT with ticagrelor and aspirin and that, while there is more bleeding than with aspirin monotherapy, it is similar to that observed in the overall population so that the balance of efficacy and safety is not associated with any excess in all-cause mortality or non-CV death.

The current analysis expands further our knowledge regarding the treatment of chronic coronary syndrome patients not receiving revascularization following an MI. The results are in contrast to the TRILOGY trial that failed to show improved outcomes with intensified antiplatelet therapy in medically managed patients treated with prasugrel and aspirin compared with clopidogrel and aspirin from the index event until ∼15 months. Although not directly comparable, the aforementioned results from the subgroups of medically managed patients in PLATO and currently in PEGASUS-TIMI 54 suggest that ticagrelor plus aspirin is effective in these patients. The other antithrombotic therapy worthy of consideration in this population of medically managed patients post-MI is the combination of rivaroxaban 2.5 mg twice daily with low-dose aspirin, although there has not been a publication directly assessing the population of patients with prior MI without revascularization. In the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial, nearly 70% of patients enrolled with coronary artery disease had suffered a prior MI on average 7 years earlier. Rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone reduced ischaemic events by 26% (MACE; HR 0.74, 95% CI 0.65–0.86).

Conclusion

In conclusion, this subgroup analysis shows that long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting.

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