Platelet Assay May Help Predict Major Bleeding after PCI

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Enhanced response to clopidogrel prior to percutaneous coronary intervention (PCI) is associated with increased risk for early major bleeding or entry-site complications, according to a study published online January 24, 2011, ahead of print in the American Journal of Cardiology. The finding suggests that measuring pre-PCI platelet reactivity with a point-of-care assay may help clinicians identify patients at increased risk and tailor their management.

Previously, several studies have linked high on-treatment platelet reactivity with an increased risk of ischemic outcomes, but a correlation between heightened platelet response and bleeding risk has not been demonstrated. To look for such an association, researchers led by Germano Di Sciascio, MD, of Campus Bio-Medico University of Rome (Rome, Italy), conducted the ARMYDA-BLEEDS (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study) trial.

ARMYDA-BLEEDS enrolled 310 consecutive clopidogrel-treated patients who underwent PCI at a single center from April 1, 2009, to December 31, 2009. Platelet reactivity was evaluated immediately before PCI and at 8 and 24 hours after intervention using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA). The primary endpoint was the 30-day incidence of major bleeding or significant entry-site complications in relation to preprocedural quartile distribution of platelet reactivity.

Pre-PCI Reactivity Correlates with 30-Day Bleeding

The overall rate of complications was 4.8%. Patients in the lowest P2Y12 reaction unit (PRU) quartile before PCI had a higher incidence of major bleeding at 1 month (10.1%) compared with those in the highest quartile (1.3%; P = 0.043) and the third quartile (1.4%; P = 0.05). Absolute PRU values before PCI were lower in patients with major bleeding at 30 days than in those without major bleeding complications (171 ± 49 vs. 227 ± 68; P = 0.002).

Multivariate analysis identified pre-PCI PRU level in the lowest quartile as an independent predictor of increased major bleeding risk at 30 days, representing a 4.5-fold increased risk for postintervention major bleeding or entry-site complications compared with the highest quartile. Age > 70 years and periprocedural use of glycoprotein IIb/IIIa inhibitors (GPIs) also were associated with a significantly higher risk for major bleeding. In addition, there was a weak trend toward increased major bleeding in patients with a body mass index (BMI) less than 22 kg/m² (table 1).

Table 1. Odds Ratios for 30-Day Major Bleeding/Entry Site Complications

Receiver-operating characteristic analysis indicated that the optimal cut-point to discriminate patients at higher risk for 30-day major bleeding is ≤ 189 PRU, with a sensitivity of 87% and specificity of 70%. The incidence of major bleeding at 1 month was 11.6% in patients with pre-PCI PRU values ≤ 189 and 1.9% in those with PRU values greater than 189 (P < 0.001).

“Thus, ARMYDA-BLEEDS confirms the usefulness of a rapid point-of-care assay for monitoring residual platelet reactivity after clopidogrel administration, to identify a clinically driven threshold of platelet reactivity defining patients at increased risk for bleeding complications, in whom individualized therapeutic strategies (ie, limited use of glycoprotein IIb/IIIa inhibitors, more extensive utilization of bivalirudin, restricted use of drug-eluting stents, and more liberal use of gastroprotective agents) may be indicated,” the study authors write.

Interesting, But More Work Needed

In a telephone interview with TCTMD, Lisa K. Jennings, PhD, of the University of Tennessee Health Science Center (Memphis, TN), said that while the results are interesting, more studies are needed to understand the clinical value of the suggested cutoffs of ≤ 189 PRU for bleeding and 240 PRU for ischemic events, as determined previously in the ARMYDA-PRO study.

“Even though someone has a value of 235 or 240, we don’t know yet if it’s solely due to clopidogrel or P2Y12 antagonist response,” she said. “We don’t understand what may cause a high reactivity vs. a low reactivity in someone on clopidogrel or what the best approach is in dealing with those patients. A physician has to take these values in the context of the history of the patient to decide what the next step might be. The other thing is that the values of 189 for bleeding and 240 for ischemic risk are very close, and I think we may need more data to tell us if this instrument really can make that kind of discrimination.”

In their discussion, Dr. Di Sciascio and colleagues suggest that because most bleeding events in the study were large entry-site hematomas, the assay also may be useful for deciding the mode of interventional access, since a radial approach might be preferable to femoral PCI in patients with a higher degree of platelet inhibition.

Dr. Jennings said the authors bring up an interesting point.

“I don’t know that this single paper would necessarily be sufficient to conclude that, but the entry-site hematomas do at least support that discussion point,” she said. “To be conclusive they would need a prospective study where that was actually addressed, but it probably would be worth pursuing.”

Source:

Patti G, Pasceri V, Vizzi V, et al. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study). Am J Cardiol. 2011;Epub ahead of print.

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