RESUMO
AIMS: Although dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remain challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6±4.0 years, females 44%) was included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4±32.1 vs. 30.4±39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; p for non-inferiority=0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29±312.36 ng/mL vs. 579.57±351.73 ng/mL, p=0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg. CONCLUSIONS: Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI. Clinical Trial registration: EudraCT 2019-002391-13. Clinicaltrials.gov NCT04739384.
RESUMO
BACKGROUND: Periprocedural myocardial infarction (MI) according to the Society for Cardiovascular Angiography and Interventions (SCAI) criteria has prognostic relevance among patients undergoing percutaneous coronary intervention (PCI). However, it is unclear whether the type of cardiac biomarker used for the diagnosis of periprocedural MI plays a role in terms of event frequency and outcomes. OBJECTIVES: To compare the characteristics of SCAI periprocedural MI based on creatine kinase-myocardial band fraction (CK-MB) vs. high-sensitivity cardiac troponin (hs-cTn) in patients undergoing elective PCI. METHODS AND RESULTS: Between 2017 and 2021, periprocedural MI was assessed in a prospective study. The primary clinical outcome of interest was all-cause death at 1-year follow-up. A total of 1010 patients undergoing elective PCI were included. SCAI periprocedural MI based on CK-MB vs. hs-cTnI occurred in 1.8 and 13.5% of patients, respectively. hs-cTnI periprocedural MI in the absence of concomitant CK-MB criteria was associated with lower rates of ancillary criteria, including angiographic, ECG, and cardiac imaging criteria. At 1-year follow-up, periprocedural MI defined by CK-MB (adjusted hazard ratio, HR, 4.27, 95% confidence intervals, CI, 1.23-14.8; P = 0.022) but not hs-cTnI (adjusted HR 2.04, 95% CI 0.94-4.45; P = 0.072) was associated with a higher risk of all-cause death. Hs-cTnI periprocedural MI was not predictive of death unless accompanied by CK-MB criteria (adjusted HR 4.64, 95% CI 1.32-16.31; P = 0.017). CONCLUSION: In the setting of elective PCI, using hs-cTn instead of CK-MB resulted in a substantial increase in SCAI periprocedural MI events, which were not prognostically relevant in the absence of concurrent CK-MB elevations.