ESC 2021: Trends and updates in ticagrelor therapy among at-risk patients

Dr. Davide Cao
Icahn School of Medicine at Mount Sinai
New York, US
Dr. Marc Bonaca
University of Colorado
Colorado, US
Dr. Wen Sun
Prince of Wales Hospital
Hong Kong
13 Nov 2021
ESC 2021: Trends and updates in ticagrelor therapy among at-risk patients

The P2Y12 inhibitor, ticagrelor, has been an important treatment for patients with acute coronary syndrome and those at risk of thrombotic events or recurrent major adverse cardiovascular events (MACE). At the European Society of Cardiology (ESC) Congress 2021, experts presented the latest trends and observations on ticagrelor therapy among patients at increased risk of cardiovascular (CV) events.

TWILIGHT substudies: Ticagrelor monotherapy in patients with HBR or CKD/DM

The TWILIGHT trial previously demonstrated that 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin followed by 12 months of ticagrelor monotherapy is associated with less bleeding vs 12 months of DAPT in patients undergoing percutaneous coronary intervention (PCI) who are at high ischaemic or bleeding risk, with no increased risk in the composite endpoint of all-cause mortality, myocarclical infarction (MI) or stroke. [N Engl J Med 2019;381:2032-2042]

Similar results were seen in patients with high bleeding risk (HBR) and those with chronic kidney disease (CKD) and/or diabetes mellitus (DM).


“TWILIGHT-HBR evaluated the effects of ticagrelor monotherapy vs DAPT on bleeding and ischaemic outcomes in a contemporary Academic Research Consortium [ARC]defined HBR population [ie, fulfilment of 1 major or two minor ARC-HBR criteria] undergoing PCI,” said Dr Davide Cao of the Icahn School of Medicine at Mount Sinai, New York, US. [Cao D, et al, ESC 2021; Eur Heat J 2019;14:2632-2653]

Among those with HBR, significantly fewer patients who received ticagrelor monotherapy experienced Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding and BARC 3 or 5 bleeding vs those who continued DAPT. (Figure) [Cao D, et al, ESC 2021]


“In patients with HBR, ticagrelor monotherapy after abbreviated DAPT post-PCI may significantly decrease clinically relevant and major bleeding events while preserving ischaemic protection vs 12 months of DAPT,” said Cao.

“There was also a significantly larger absolute risk difference [ARD] in BARC 3 or 5 bleeding among HBR vs non-HBR patients [-3.5 percent vs -0.5 percent; ARD difference, 3.0 percent; p=0.008], highlighting the benefit of ticagrelor monotherapy as a bleeding avoidance strategy in this vulnerable cohort,” said Cao.


“Similarly, TWILIGHT CKD-DM showed that ticagrelor monotherapy reduced the risk of clinically relevant and major bleeding, with no significant increase in ischaemic events, vs continued DAPT in patients with concomitant DM and/or CKD,” said Cao. [Cao D, et al, ESC 2021]

“Ticagrelor monotherapy may be associated with a more favourable net benefit [ie, lower bleeding and ischaemic events] among those with DM but no CKD,” noted Cao. “In this population, significantly fewer patients on ticagrelor monotherapy experienced the ischaemic composite endpoint vs continued DAPT [3.3 percent vs 5.7 percent; hazard ratio (HR), 0.58; 95 percent confidence interval (CI), 0.37 to 0.92; pinteraction=0.033].”

ALETHEIA real-world study: Ticagrelor 60 mg in post-MI patients

PEGASUS-TIMI 54 previously demonstrated that extended DAPT with ticagrelor 60 mg or 90 mg BID and aspirin was associated with a lower risk of MACE (ie, CV death, MI or stroke) and an increased risk of major bleeding vs aspirin monotherapy in patients who had an MI >1 year ago. [N Engl J Med 2015;372:1791-1800]

“Although ticagrelor 60 mg BID is currently the approved dose for these patients, treatment outcomes and the characteristics of patients on this regimen in the real-world setting are not well described,” said Dr Marc Bonaca of the University of Colorado in Aurora, Colorado, US. [Brilinta Hong Kong prescribing information]  “ALETHEIA is the first international observational registry study in the US and Europe that aims to describe the characteristics and treatment outcomes of post-MI patients receiving long-term ticagrelor at 60 mg in the real world.” [Bonaca M, et al, ESC 2021; Clin Cardiol 2021;doi:10.1002/clc.23702]

Initial key results showed that patients included in this registry were generally similar to those in PEGASUS-TIMI 54, but with higher baseline CV risk (ie, greater prevalence of peripheral arterial disease, prior bleeding, and shorter median time from previous MI). At 2 years, the cumulative incidence of the composite CV outcome (ie, all-cause mortality and hospitalization for MI or stroke) was 6.30 percent, excluding the smallest country in the analysis. The rate of bleeding requiring hospitalization was 0.96 percent in the first year and decreased over time (second year, 0.56 percent). [Bonaca M, et al, ESC 2021]

DAPT in Chinese patients with stable CAD and DM

“We conducted a retrospective analysis to determine the potential benefits of DAPT with ticagrelor and aspirin among Chinese patients in Hong Kong with stable coronary artery disease [CAD] and type 2 DM [T2DM] with or without a history of PCI,” said Dr Wen Sun of the Prince of Wales Hospital, Hong Kong. [Sun W, et al, ESC 2021]

The THEMIS trial previously demonstrated that patients
50 years of age with stable CAD and T2DM who received ticagrelor plus aspirin had a lower incidence of ischaemic CV events but a higher incidence of major bleeding vs those who received placebo plus aspirin, regardless of PCI history. [N Engl J Med 2019;381:1309-1320; Lancet 2019;394:1169-1180]

“Our results showed that approximately one-third of patients with stable CAD and T2DM met the THEMIS criteria. Their estimated baseline risk of MI and MACE was 7.2 percent and 14.7 percent at 36 months, respectively,” noted Sun. These were approximately twice as high as the corresponding risks in the placebo arm of THEMIS (3.3 percent and 7.6 percent, respectively). [Sun W, et al, ESC 2021; N Engl J Med 2019;381:1309-1320]

Ticagrelor plus aspirin was estimated to provide up to 1.5 percent and 1.4 percent absolute risk reduction (ARR) in MI and MACE, respectively. In the subgroup of patients who underwent previous PCI, DAPT may provide even greater benefits (ie, 1.9 percent and 1.6 percent estimated ARR in MI and MACE, respectively). [Sun W, et al, ESC 2021]

“These results demonstrate that ticagrelor plus aspirin may provide substantial and greater benefits in Chinese patients with stable CAD and T2DM, especially those who underwent prior PCI, compared with that observed in the THEMIS trial,” concluded Sun.

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