ESC 2017 - Barcelona

Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54

Gepresenteerd op het ESC congres 2017 door: Mikael Dellborg (Gothenburg, Germany)

Background

In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular events (MACE; CV death, MI or stroke) by 15–16% in stable patients with a prior MI

1–3 years earlier. The benefit of ticagrelor appeared more marked in patients continuing on or restarting after only a brief interruption of adenosine diphosphate (ADP) receptor inhibition and in those closer to their qualifying MI.

The CHMP-EMA approved European label recommends that after the initial one-year treatment with ticagrelor 90 mg bd in ACS patients, treatment with ticagrelor 60 mg bd may be started without interruption as continuation therapy. Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment.

This is an analysis of efficacy and bleeding safety in the PEGASUS subpopulation recommended for treatment in the European label. PEGASUS-TIMI 54 randomized 21,162 patients who had had an MI 1–3 years earlier to ticagrelor at a dose of 90 or 60 mg, or placebo. 10,779 patients were ≤2 years from qualifying MI or ≤1 year from prior ADP receptor inhibitor treatment, 5388 in the ticagrelor 60 mg and 5391 in the placebo group.

Main results

• The composite of CV death, MI or stroke occurred in 373 patients (KM rate 7.9%) in the ticagrelor 60 mg group and in 463 patients (KM rate 9.6%) in the placebo group; HR 0.80 (95%CI: 0.70-0.91;

p=0.001). Corresponding HRs for CV death, MI and stroke were 0.71 (95%CI: 0.56-0.90; p=0.0041), 0.83 (95%CI: 0.70-0.99; p=0.041) and 0.74 (95%CI: 0.55-1.01; p=0.058), respectively.

• Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (95%CI: 0.67-0.96; p=0.018).
• TIMI major bleeding occurred in 94 patients (KM rate 2.5%) in the ticagrelor group and in 43 patients (KM rate 1.1%) in the placebo group; HR 2.36 (95%CI: 1.65, 3.39, p<0.001).
• The corresponding HR for fatal or intracranial bleeding (n=27 ticagrelor vs 25 placebo) was 1.17 (95%CI: 0.68-2.01;p=0.58).

Conclusion

Treatment with ticagrelor 60 mg, either as continuation therapy after the initial 12 month post-MI period, or with as limited interruption as possible after ADP receptor blocker discontinuation, as recommended in the European label, was associated with relative risk reductions in the composite of CV death, MI or stroke, in CV mortality and all-cause mortality. An increase in TIMI major bleedings was observed with ticagrelor, while fatal or intracranial bleeding was comparable to placebo. These findings resulted in a favourable beneft-risk ratio for long-term ticagrelor 60 mg in this patient population.

- Our reporting is based on the information provided in a press release after the ESC congress -