High Platelet Reactivity Signals High Risk of Ischemic Events

View on the News

Role of Platelet Function Testing Still Unclear

Despite the promising results of this and other studies, the currently available evidence "cannot support the routine use of platelet function testing in clinical practice. Until results of appropriately powered randomized controlled trials demonstrate efficacy and safety (in particular, low bleeding risk) of adjustment of antiplatelet treatment, platelet function testing should be reserved mostly as a research tool," said Dr. Dominick J. Angiolillo.

Since adjusting antiplatelet therapy on the basis of platelet function testing did not improve patient outcomes in this study, clinicians are left "without an answer about what to do with the results of platelet function testing," he noted. It also remains unknown "whether platelet reactivity is simply a marker of risk or if it is a modifiable risk factor that can affect prognosis."

Dominick J. Angiolillo, M.D., Ph.D., is at the University of Florida, Jacksonville. He reported ties to numerous industry sources. These remarks were taken from his editorial accompanying Dr. Parodi’s report (JAMA 2011;306:1260-1).



ACS patients who show high residual platelet reactivity in response to clopidogrel on platelet function testing are at increased risk of ischemic events in both the short term and the long term, according to a prospective, observational study reported in the September 21 issue of JAMA.

In particular, these patients’ risk of cardiac mortality is twice as high (9.7%) as that of patients who do not show high residual platelet reactivity on platelet function testing (4.3%), said Dr. Guido Parodi of the department of cardiology, Careggi Hospital, Florence, and his associates.

To assess whether residual platelet reactivity to clopidogrel may be a prognostic marker, the investigators performed a prospective observational cohort study of 1,789 consecutive patients with acute coronary syndromes who were undergoing percutaneous coronary intervention (PCI) with stent implantation at a single center over a 4-year period. Platelet reactivity was tested using light transmittance aggregometry with an adenosine diphosphate (ADP) agonist, 12-18 hours after administering a 600-mg loading dose of clopidogrel.

The overall incidence of high residual platelet reactivity by ADP testing was 14%, which was considered relatively low.

The primary end point was a composite of ischemic events including cardiac death, MI, urgent coronary revascularization, and stroke during 2 years of follow-up. This end point developed in 14.6% of patients with high residual platelet reactivity, compared with only 8.7% of the other patients.

"The difference in the primary end point event rate was driven by the difference in cardiac mortality, which was 9.7% in the high residual platelet reactivity group and 4.3% in the low residual platelet reactivity group; there were no differences in the other components of the primary end point," the investigators said (JAMA 2011;306:1215-23).

The higher rate of cardiac mortality emerged within 6 months of baseline and persisted throughout follow-up, they noted.

The secondary end point of stent thrombosis also was twice as high in patients with high residual platelet reactivity (6.1%) as in other patients (2.9%).

These results support the hypothesis that high residual platelet reactivity in response to clopidogrel is a prognostic marker for ischemic events.

Of note was the finding that normalization of platelet reactivity did not improve outcomes, compared with persistent platelet reactivity.

Patients who initially showed high residual platelet reactivity in response to clopidogrel underwent an adjustment of therapy to rectify the problem. An ADP-guided increase in maintenance clopidogrel dose or an ADP-guided switch to ticlopidine led to normalized reactivity in 62% of this group and but did not affect the other 38%, who continued to show persistently high reactivity. Yet outcomes were not significantly different between these two groups.

This study was supported by the Italian Health Ministry. Dr. Parodi and his associates reported ties to numerous industry sources.

Recommended Reading

Quick Cooling With Therapeutic Hypothermia Improves Neurologic Outcomes in Certain Patients
MDedge Cardiology
High Sodium-Potassium Ratio Ramps Up Mortality Risk
MDedge Cardiology
'Late' PCI Still Common Though Guidelines Advise Against It
MDedge Cardiology
Protocol Shrinks Ruptured Abdominal Aortic Aneurysm Treatment Time
MDedge Cardiology
Editorial: Angiography in Asymptomatic Patients
MDedge Cardiology
Carvedilol Reduces Intradialytic Hypertension
MDedge Cardiology
Remote Ischemic Preconditioning Beneficial in Peripheral Occlusive Disease
MDedge Cardiology
Genes Play Bigger Role in MI Than Stroke
MDedge Cardiology
Point/Counterpoint: Is Early Discontinuation of Steroids Right for Heart Transplant Recipients?
MDedge Cardiology
Arrhythmia Risk Leads to Ondansetron Label Changes
MDedge Cardiology