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Patient selection for long-term secondary prevention with ticagrelor: insights from PEGASUS-TIMI 54
Marc P Bonaca1, KyungAh Im2, Giulia Magnani3
1Department of Cardiology and Vascular Medicine, University of Colorado School of Medicine, 2115 N Scranton St Suite 2040, Aurora, CO 80045, USA.
Insights
Long-term ticagrelor therapy in patients with prior myocardial infarction (MI) reduces ischemic risk but increases bleeding. It is most beneficial for patients with multiple ischemic risk factors and low bleeding risk.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Patients with prior myocardial infarction (MI) on aspirin face increased bleeding risk with ticagrelor.
- Assessing both ischemic and bleeding risk is crucial for optimal ticagrelor use.
Purpose of the Study:
- To evaluate the risk-benefit profile of long-term ticagrelor in prior MI patients based on bleeding and ischemic risk.
- To identify patient subgroups most likely to benefit from ticagrelor therapy.
Main Methods:
- The PEGASUS-TIMI 54 trial randomized 13,956 prior MI patients to ticagrelor or placebo.
- Patients were stratified into groups based on bleeding predictors and ischemic risk factors (IRFs).
- Primary efficacy endpoint: cardiovascular death, MI, or stroke; primary safety outcome: TIMI major bleeding.
Main Results:
- In high bleeding risk patients, ticagrelor increased bleeding and did not reduce the primary efficacy endpoint.
- In low bleeding risk patients, ticagrelor showed greater efficacy with increasing numbers of IRFs (≤1, 2, or ≥3).
- Significant trends for greater risk reduction in cardiovascular death, all-cause mortality, and net outcomes were observed with ticagrelor across low bleeding risk groups with more IRFs.
Conclusions:
- Long-term ticagrelor therapy is most suitable for prior MI patients with multiple ischemic risk factors and low bleeding risk.
- Risk stratification is essential for tailoring ticagrelor therapy to individual patient profiles.
- Further research may refine patient selection for optimal ticagrelor use.
Aim:
In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor.
Methods And Results:
PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups.
Conclusion:
In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk.
Clinical Trial Registration:
NCT01225562 ClinicalTrials.gov.
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