Improved platelet inhibition with ticagrelor when compared to clopidogrel in peripheral artery disease patients

Clopidogrel and ticagrelor are well-known antiplatelet drugs that inhibit P2Y12 receptors. Although clopidogrel is currently the standard of care for peripheral artery disease (PAD), 25% of patients are known to exhibit drug resistance due to genetic variability. Ticagrelor presents an alternative with reduced susceptibility to genetic variations and has demonstrated superior outcomes in acute coronary syndromes. However, ticagrelor currently lacks a formal indication for PAD management. This study aims to compare the clot strength and platelet function in patients with PAD transitioning from aspirin-clopidogrel to aspirin-ticagrelor using thromboelastography with platelet mapping (TEG-PM).

Patients with PAD who underwent revascularization surgery at a single tertiary center were enrolled from December 2022 to December 2024. TEG-PM analysis was performed at baseline, 1 week, 1 month, 3 months, and 6 months. Patients who switched from clopidogrel to ticagrelor were included in this study. Consenting patients also underwent VerifyNow testing for clopidogrel resistance. Statistical analysis used descriptive statistics and the Wilcoxon matched-pairs test to compare TEG-PM parameters.

In our cohort of 35 patients (mean age 66.49 ± 10.74 years, 65.7% male), significant differences were observed in platelet function parameters. Adenosine diphosphate-mediated maximum amplitude that depicts clot strength was significantly lower with ticagrelor compared with clopidogrel (50.8 mm vs 59.5 mm, P < .0001). Ticagrelor also showed superior platelet inhibition (30.90% vs 13.40%, P = .0001). One bleeding event (defined as clinically significant hemorrhage that required medical intervention or transfusion) occurred on ticagrelor, whereas two thrombotic events (defined as arterial graft/stent occlusion or stenosis) were documented on clopidogrel. VerifyNow testing revealed that 34.6% of the patients (9 of 26) were resistant to clopidogrel (P2Y12 reaction units >180).

Ticagrelor demonstrated superior platelet inhibition to clopidogrel in patients with PAD after revascularization. The high prevalence of clopidogrel resistance underscores the potential clinical benefit of ticagrelor for patients with PAD after revascularization.