Ticagrelor after abbreviated DAPT minimizes bleeding while preserving efficacy in ACS

Jairia Dela Cruz
12 Oct 2021

Monotherapy with ticagrelor after a month-long course of dual antiplatelet (DAPT) with ticagrelor plus aspirin works to reduce the risk of bleeding without compromising ischaemic outcomes among patients with acute coronary syndrome (ACS) as compared with guideline-recommended treatment with 12-month DAPT followed by aspirin monotherapy, according to data from the GLOBAL LEADERS trial.

However, the experimental treatment strategy does not seem to benefit patients with stable coronary artery disease (SCAD), with ticagrelor monotherapy producing a nonsignificant increase in the risk of bleeding.

“In this prespecified subgroup analysis of the GLOBAL LEADERS trial, we analysed prespecified efficacy and safety endpoints according to clinical presentation throughout 2 years,” the investigators said.

Of the 7,487 patients in the ACS cohort, 3,750 were randomized to the experimental treatment strategy and 3,737 to the reference treatment strategy. Meanwhile, of the 8,481 patients in the SCAD cohort, 4,230 were assigned to the experimental group and 4,251 to the reference group.

Patients in the experimental group received 75–100-mg aspirin daily plus 90-mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy. Those in the reference group were given 75–100-mg aspirin daily plus either 75-mg clopidogrel daily (for SCAD) or 90-mg ticagrelor twice daily (for ACS) for 12 months, followed by aspirin monotherapy for 12 months.

The ACS cohort was younger, had a lower body mass index, and lower prevalence of cardiovascular risk factors or prior cardiovascular events (eg, stroke, MI, or coronary revascularization) as compared with the SCAD cohort.

At year 2, the primary efficacy endpoint of a composite of all‐cause mortality or nonfatal centrally adjudicated new Q‐wave MI with the experimental and reference treatment strategies occurred in 3.92 percent and 4.52 percent of ACS patients and in 3.71 percent and 4.23 percent of SCAD patients, respectively. The difference between the two treatment strategies was not significant in both the ACS (rate ratio [RR], 0.86, 95 percent confidence interval [CI], 0.69–1.08; p=0.189) and SCAD cohorts (RR, 0.87, 95 percent CI, 0.71–1.08; p=0.221; pinteraction=0.926). [J Am Heart Assoc 2021;doi:10.1161/JAHA.119.015560]

“Furthermore, there was no evidence for differences in treatment effects between subgroups in terms of investigator reported myocardial infarction, stroke, or definite stent thrombosis,” the investigators noted.

Conversely, a treatment‐by‐subgroup interaction emerged in the key secondary safety endpoint of site‐reported Bleeding Academic Research Consortium (BARC) grade 3 or 5 bleeding. This outcome occurred in significantly fewer patients who underwent the experimental vs the reference treatment strategy in the ACS cohort (1.95 percent vs 2.68 percent; RR, 0.73, 95 percent CI, 0.54–0.98; p=0.037), but in slightly higher number of patients who received the experimental vs the reference strategy in the SCAD cohort (2.13 percent vs 1.62 percent; RR, 1.32, 95 percent CI, 0.97–1.81; p=0.081; pinteraction=0.007).

The safety findings are consistent with those reported in the TWILIGHT (Ticagrelor with Aspirin or Alone in High‐Risk Patients after Coronary Intervention) trial, which included a higher ischaemic risk patient population undergoing treatment with ticagrelor monotherapy after 3 months of DAPT compared with DAPT using aspirin and ticagrelor for the duration of 12 months. Specifically, ticagrelor monotherapy reduced the incidence of BARC 2, 3, or 5 bleeding by 53 percent in the subgroup of patients with ACS. [N Engl J Med 2019;381:2032-2042]

“Taken together, the TWILIGHT trial and our subgroup analysis suggest … that withdrawal of aspirin after a short period of DAPT and continued treatment with ticagrelor monotherapy may represent a safer alternative to the current guideline-recommended treatment for reducing recurrent ischaemic events in patients with ACS,” the investigators pointed out.

Seeing that ticagrelor monotherapy following an abbreviated treatment with DAPT may provide an optimal balance between ischaemic and bleeding risk in ACS, this treatment strategy therefore deserves further study, they added.

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