Ticagrelor displays net clinical benefit in GLOBAL LEADERS

Subgroup evaluations of the GLOBAL LEADERS trial demonstrated the anti-ischaemic efficacy of long-term ticagrelor monotherapy relative to aspirin monotherapy in patients who had percutaneous coronary intervention (PCI). However, this occurred at the expense of bleeding in the elderly.

In GLOBAL LEADERS (n=15,991; mean age 65 years, 23 percent women), investigators compared a regimen comprising 23 months of ticagrelor monotherapy following 1 month of dual antiplatelet therapy (DAPT; experimental arm) against a regimen of 1-year aspirin monotherapy after 1 year of DAPT (reference arm). The primary endpoint was a composite of all-cause death and new Q-wave myocardial infarction. Duration of follow-up was 2 years.

In the subgroup of patients with long stenting (≥46 mm; n=3,884), the experimental strategy significantly reduced the incidence of the primary endpoint vs the reference regimen (3.79 percent vs 5.68 percent; hazard ratio [HR], 0.66, 95 percent confidence interval [CI], 0.49–0.89; p=0.006). The rates of bleeding (BARC* type 3 or 5) were similar between the two arms (2.53 percent vs 2.55 percent; HR, 0.99, 95 percent CI, 0.67–1.48; p=0.968). [ESC Congress 2019, abstract P2811]

This net clinical benefit was mirrored in the subgroup of participants with multivessel PCI (n=3,576), wherein the experimental regimen still fared better than the reference strategy in terms of reducing the incidence of the primary endpoint (3.05 percent vs 4.85 percent; HR, 0.62, 95 percent CI, 0.44–0.88; p=0.006) but not bleeding (2.44 percent vs 2.65 percent; HR, 0.92, 95 percent CI, 0.61–1.39; p=0.685). [ESC Congress 2019, abstract P2812]

“[Our findings] demonstrated that the experimental antiplatelet strategy, when compared with the reference regimen, [might] have a favourable balance between ischaemic efficacy and bleeding safety in patients who underwent multivessel PCI,” said the investigators.

Greater bleeding risk in the elderly

Among participants aged >75 years (n=2,565), the experimental strategy led to a lower incidence of the primary endpoint compared with the reference regimen (7.2 percent vs 9.4 percent; HR, 0.75, 95 percent CI, 0.58–0.99; p=0.041) though at the cost of a borderline but nonsignificant excess bleeding risk (5.0 percent vs 3.9 percent; HR, 1.29, 95 percent CI, 0.89–1.86; p=0.180). [ESC Congress 2019, abstract P2531]

This appeared to be specific to elderly patients with stable coronary artery disease (CAD) in the experimental arm who had a reduced incidence of the primary endpoint (5.7 percent vs 8.4 percent; p=0.046) but an increase in bleeding (5.3 percent vs 2.6 percent; p=0.012). In contrast, among those with acute coronary syndrome (ACS), there was no difference between the experimental and reference arms in terms of the incidence of the primary endpoint (9.1 percent vs 10.8 percent; p=0.367) or bleeding (4.7 percent vs 5.7 percent; p=0.458).

“[Although] the efficacy and safety of the experimental strategy … was not identified as age-dependent … [our findings showed that] the anti-ischaemic benefit [among the elderly] was derived at the expense of increased rate of … bleeding in the stable CAD but not in the ACS subgroup,” said the researchers.

“[Nonetheless, these findings] must be looked upon cautiously since the trial was not designed for this purpose nor powered for it; thus, the results should be considered as only hypothesis generating,” they added.