High Platelet Reactivity May Increase Culprit Lesion Atherosclerotic Burden with PCI

Patients undergoing percutaneous coronary intervention may have increased culprit lesions and adverse plaque morphology caused by high on-treatment platelet reactivity.

High on-treatment platelet reactivity (HPR) may cause increased culprit lesion atherosclerotic burden and adverse plaque morphology among patients undergoing percutaneous coronary intervention (PCI), according to research published in JACC: Cardiovascular Imaging.

Researchers conducted a sub-study from the ADAPT-DES (Assessment From the Dual AntiPlatelet Therapy With Drug-Eluting Stents) trial, which included 8582 patients undergoing PCI with drug-eluting stents. The original study assessed platelet reactivity in patients treated with clopidogrel.

“HPR may not only be associated with MI or stent thrombosis, but also may be associated with increased coronary atherosclerotic burden or unstable plaque morphology,” researchers wrote. “Recent angiographic and intravascular ultrasound (IVUS) studies have reported that HPR is associated with multivessel disease and higher plaque volume; however, plaque morphology has not been evaluated.”

They analyzed 909 culprit lesions from 773 patients with pre-intervention grayscale IVUS and virtual histology (VH)-IVUS. HPR was defined as platelet activity greater than 208 in point-of-care P2Y12 testing, which was measured during the steady state platelet inhibition in patients receiving an antiplatelet agent.

Incidence of 3 vessel coronary artery disease was higher among patients with HPR than those without HPR (31.0% vs 24.4%; P=.04) as was the incidence fibroatheroma (77.1% vs 68.9%; P=.01).

Patients in the HPR group also had larger amounts of plaque and media volume. The plaque and media/external elastic membrane volume was 58.1% (95% confidence interval [CI]: 57.1-59.0) among patients with HPR vs 56.6% (95% CI: 55.8%-57.5%) among patients without HPR (P=.03). In addition, the plaque burden at the minimum lumen site was 76.7% (95% CI: 75.7%-77.8%) among patients with HPR vs 75.0% (95% CI: 74.0%-76.0%) among patients without HPR (P=.02).

Patients with HPR also had longer culprit lesion attenuated plaque length despite a similar prevalence of attenuated plaque (8.0 mm [95% CI: 7.0-9.1 mm] vs 6.5 mm [95% CI: 5.9-7.1 mm]; P=.01).

A multivariate analysis revealed that the presence of angiographic calcium (odds ratio [OR]: 1.85; 95% CI: 1.33-2.56; P=.0002) and HPR (OR: 1.45; 95% CI: 1.05-2.01; P=.02) were independent predictors for a culprit lesion fibroatheroma.

“The cause-and effect relationship between platelet reactivity and plaque morphology remains speculative,” the authors noted. “Further studies are required to define the casual mechanisms between platelet reactivity and development and progression of atherosclerosis and whether this may be a contributing factor in future cardiovascular events.”


Yun KH, Mintz GS, Witzenbichler B, et al. Relationship between platelet reactivity and culprit lesion morphology: An assessment from the ADAPT-DES intravascular ultrasound substudy. JACC Cardiovasc Imag. 2016. doi: 10.1016 /j.jcmg.2015.08.019.