ACCEL-BLEED: Mild Bleeding Correlated with Platelet Reactivity One Month Post PCI

SAN FRANCISCO, CA—In East Asian patients on antiplatelet therapy following percutaneous coronary intervention (PCI), levels of platelet reactivity at 1 month predict the risk of internal bleeding, according to data presented at TCT 2011.

For the prospective, single-center ACCEL-BLEED study, Young-Hoon Jeong, MD, PhD, of Gyeongsang National University Hospital (Jinju, South Korea), and colleagues observed 305 stented patients who underwent platelet function testing with light transmittance aggregometry (LTA; AggRAM, Helena Laboratories, Beaumont, TX) and the VASP-P assay (BioCytex, Marseille, France) both in-hospital and at 1 month follow-up. About three quarters of patients also were genotyped. Platelet reactivity measurements were correlated with various bleeding events at 30 days.

At 1 month post discharge, there were no cases of TIMI minor or major bleeding or moderate to severe GUSTO bleeding. However, by BleedScore classification, 22.3% of patients experienced superficial bleeding (including easy bruising and bleeding from small cuts or tooth brushing) and 7.0% had internal bleeding (including nosebleed and bloody stool), while none had ‘alarming’ bleeding.

While in-hospital LTA showed no difference across the bleeding categories, LTA measurements at 1 month indicated that ADP-induced platelet aggregation for internal bleeding was significantly lower compared with no bleeding (39.2% vs. 50.1%; P = 0.03). Likewise, in-hospital VASP index measurements were similar across the bleeding groups, whereas 1-month VASP-P index levels were lower in the internal bleeding group than the no- bleeding group (figure 1).

In ROC analysis, 20 µM ADP-induced maximal platelet aggregation (MPA) ≤ 44.5% (P = 0.03) and VASP index ≤ 45.5% (P = 0.06) were determined to be the optimal cutoff points for predicting internal bleeding. The former yielded a sensitivity and specificity of 0.62, and the latter a sensitivity of 0.73 and a specificity of 0.57. In total, 25.6% of patients fell below the ADP-MPA threshold and 38.2% were under the VASP index threshold.

In multivariate analysis, only a platelet count of ≥ 270x10³/mm³ at 1 month predicted reduced risk of superficial bleeding vs. no bleeding (OR 0.37; 95% CI 0.17-0.81; P = 0.01). In addition, the 20 µM ADP-MPA cutpoint predicted internal vs. no bleeding (OR 2.56; 95% CI 1.00-6.58; P = 0.05), while the VASP-P index cutpoint made the same prediction (OR 3.25; 95% CI 1.25-8.40; P = 0.02).

Should Antiplatelet Therapy Be Guided by Ethnicity?

When bleeding events were assessed according to CYP2C19 genotype, superficial bleeding showed no interaction with phenotype, but internal bleeding decreased proportionally with increasing number of CYP2C19*2 loss-of-function alleles.

Dr. Jeong concluded that platelet reactivity cutoffs to predict internal bleeding in East Asians are not that different from those for consensus-defined, high on-treatment platelet reactivity for ischemic events. At the same level of on-treatment platelet reactivity, East Asians may be more likely to bleed than Caucasians, suggesting that the therapeutic window for antiplatelet therapy may vary with ethnicity.

BleedScore classification can be used to link platelet reactivity levels to safety profiles in antiplatelet trials, he observed, but the validity of this metric for long-term clinical outcomes remains to be determined. Moreover, dedicated studies are needed to assess the efficacy and safety of the new potent P2Y12 receptor antagonists in East Asian populations, he added.

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