Compared with aspirin monotherapy, the P2Y12 receptor inhibitor clopidogrel was associated with better endothelial function, greater platelet inhibition, and lower coagulation activity in patients with coronary artery disease (CAD), according to the results of a study published in the Journal of Clinical Medicine.

The findings suggest that the antiplatelet medication has pleiotropic effects on endothelial function and hemostatic profiles.

The prospective, randomized, open-label, 2-way superiority crossover study, I-LOVE-MONO (Impact of cLOpidogrel VErsus aspirin MONOtherapy on endothelial function), was conducted at 2 centers in South Korea between August 2018 and April 2019.

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Participants, who had moderate-to-high ischemic risk, had undergone percutaneous coronary intervention with angioplasty and received a drug-eluting stent in addition to dual antiplatelet therapy (100 mg aspirin, once daily, and clopidogrel, 75 mg, once daily) for at least 6 months. Patients were randomly assigned to receive either clopidogrel (75 mg) or aspirin (100 mg) daily for 4 weeks. Then, the patients were crossed over to the other therapy for 4 weeks. Measures of vascular function and hemostatic profiles were evaluated. The primary endpoint was the reactive hyperemia index (RHI).

Overall, 30 patients were enrolled in the study, of whom 26 completed both periods of the study with complete adherence. Patients had an average age of 60.4 years and were predominantly male (92.3%).

Compared with aspirin monotherapy, clopidogrel was associated with better endothelial function (RHI, 2.11% vs 1.87%; P =.045), lower platelet reactivity (130 vs 214 P2Y12 reaction unit [PRU]; P <.001), and prolonged thromboelastographic reaction time (TEG R, 5.5 vs 5.1 min, P =.037).

In a multivariate analysis, normal endothelial function (RHI ≥2.1) was associated with clot kinetics (TEG angle ≤68 degree; odds ratio (OR), 7.4; 95% confidence interval (CI), 1.44-38.09; P =.016) and platelet reactivity of ≤132 PRU (OR, 4.02; 95% CI, 1.08-14.92; P =.037). Platelet reactivity of ≤132 PRU was achieved in 46.2% of patients during clopidogrel administration compared with 3.8% of patients during aspirin monotherapy (OR, 21.4; 95% CI, 2.7-170.1; P <.001).

Limitations of the study included the small study population, which included only East Asian patients and comprised predominantly male patients, a short duration of treatment, and the lack of monotherapy with a potent P2Y12 inhibitor.

“To the best of our knowledge, the I-LOVE-MONO trial was the first investigation to compare vascular function (endothelial function and arterial stiffness indices) and hemostatic measurements (platelet function and global hemostasis assay) during monotherapy with clopidogrel vs. aspirin in CAD patients with moderate-to-high ischemic risk,” wrote the authors. “[The] pleiotropic effects of clopidogrel may inhibit atherothrombotic progression and improve future CV outcomes.”

Disclosure: This research was partially supported by Hanmi Pharmaceutical Co., Ltd. Please see the original reference for a full list of disclosures.


Park HW, Kang MG, Ahn JH, et al. Effects of monotherapy with clopidogrel vs. aspirin on vascular function and hemostatic measurements in patients with coronary artery disease: The prospective, crossover I-LOVE-MONO trial. J Clin Med. 2021;10(12):2720. doi:10.3390/jcm10122720