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Brilinta Questioned for Acute Coronary Syndrome

— Improvements in stent technology may call for rethink on P2Y12 inhibition

MedpageToday

With modern stents, a more potent antiplatelet is not necessarily going to help heart attack survivors after percutaneous coronary intervention (PCI), a cohort study suggested.

Individuals who underwent PCI for acute coronary syndrome (ACS) did not have favorable outcomes on ticagrelor (Brilinta) compared to clopidogrel (Plavix) in data from Alberta's provincial registry.

In the year following hospital discharge, Michelle Graham, MD, of the University of Alberta in Edmonton, and colleagues reported that ticagrelor was associated with:

  • No reduction in major adverse coronary events (MACE; all-cause death, hospitalization for ACS, unplanned coronary revascularization, and stent thrombosis): 10.3% versus 11.6% with clopidogrel (adjusted HR 0.97, 95% CI 0.85-1.10)
  • More hospitalization for major bleeding (6.8% vs 6.3%, adjusted HR 1.51, 95% CI 1.29-1.78)
  • More emergency department visits for dyspnea (2.9% vs 1.6%, adjusted HR 1.98, 95% CI 1.47-2.65)

"In aggregate, these study findings suggest that the increased potency of ticagrelor may not translate to improved efficacy in the era of second-generation drug-eluting stents, particularly after patients are hospital discharged," the study authors concluded in the report.

Switching from clopidogrel to ticagrelor did not improve outcomes for patients stented for ACS in a recent Dutch study either.

Current ACS guidelines recommend ticagrelor over clopidogrel for use alongside aspirin in dual antiplatelet therapy, based primarily on the that showed a clinical benefit to the stronger P2Y12 inhibitor in 2009, Graham's team noted.

Back then, however, PCI was predominantly performed using bare metal stents and first-generation drug-eluting stents.

Graham's population-based cohort study was based on the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. The 11,185 individuals included had all been prescribed either P2Y12 inhibitor within 31 days after PCI, according to pharmacy records, and were assumed to be taking aspirin 81 mg daily during follow-up.

Median age of these ACS survivors was 61 years, and a quarter were women.

The 36.4% of ticagrelor users in the cohort tended to be younger with fewer comorbidities. Ticagrelor users were also more likely to adhere to P2Y12 inhibitor therapy, with prescription refill rates of 80% or better, in the first year after hospital discharge (81.6% vs 73.9% with clopidogrel, P<0.001).

Thus, comparisons between the two groups in the study were adjusted for these differences in baseline characteristics and adherence. Subgroup results were consistent with the main findings.

Graham and colleagues found that better adherence to P2Y12 inhibitors was associated with lower MACE risk (adjusted HR 0.79, 95% CI 0.69-0.90) -- a stronger association than choice of the P2Y12 inhibitor itself.

"These results should encourage clinicians to routinely ask patients whether they are taking their medications as prescribed and identify and resolve barriers to adherence, including cost, adverse events (including dyspnea with ticagrelor), and burden from number or frequency of medications administered," the group wrote.

Chief among the limitations of the study was inability to exclude residual unmeasured confounding due to the observational design. The authors also acknowledged that they had no information on adverse events occurring during the index hospitalization and that they may have overestimated true adherence to antiplatelet therapy.

  • author['full_name']

    Nicole Lou is a reporter for 51˶, where she covers cardiology news and other developments in medicine.

Disclosures

Graham had no disclosures.

Study co-authors listed various ties to industry.

Primary Source

JAMA Internal Medicine

Turgeon RD, et al "Association of ticagrelor vs clopidogrel with major adverse coronary events in patients with acute coronary syndrome undergoing percutaneous coronary intervention" JAMA Intern Med 2020; DOI: 10.1001/jamainternmed.2019.6447.