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A meta-analysis of studies that used the same clopidogrel (Plavix) responsiveness test confirmed that high platelet reactivity during percutaneous coronary intervention (PCI) predicts mortality and other longer-term risks.
The highest residual levels predicted a 2.62-fold higher risk of death, myocardial infarction (MI), or stent thrombosis compared with the lowest on-treatment levels (P<0.001), Somjot S. Brar, MD, MPH, of Kaiser Permanente in Los Angeles, and colleagues found.
Each additional 10 units of platelet reactivity increased the composite risk 4% (P<0.0001), the group reported in the Nov. 1 issue of the Journal of the American College of Cardiology.
These results from patient-level analysis of six studies with the VerifyNow assay for the P2Y12 adenosine diphosphate receptor clopidogrel blocks help answer some of the issues that stand in the way of wider adoption of platelet testing, an accompanying editorial noted.
Most evidence has come from single-center series and some have used assays that are not widely available or standardized, or that require qualified laboratory staff, wrote Stephen D. Wiviott, MD, of the TIMI Study Group at Harvard, and Willibald Hochholzer, MD, of the Herz-Zentrum Bad Krozingen, Germany.
Yet the biggest hurdle is showing that intervention based on the assay results can not only reduce residual platelet reactivity but also improve clinical outcomes, the editorialists explained.
Trials such as GRAVITAS and TRIGGER-PCI haven't shown any effect from doubling the clopidogrel dose or switching to prasugrel (Effient). However, these trials suffered from low event rates and other limitations that leave the issue unsettled, they noted.
All six studies in the pooled meta-analysis used the same point-of-care assay at the time of PCI for those pretreated with clopidogrel or at least one day after the loading dose of the drug.
Among the 3,059 patients included, the two-year risk of death, MI, or stent thrombosis rose with residual level of platelet reactivity (P<0.001). The rates were:
- 5.8% for those in the lowest quartile at a median 84.5 platelet reactivity units (PRU)
- 6.9% for those in the second quartile at a median 171 PRU
- 10.9% for those in the third quartile at a median 229.7 PRU
- 15.8% for those in the highest quartile at a median 301 PRU
This risk was significantly elevated for those above the overall average, at a 1.82-fold risk for those in the third quartile and 2.62-fold risk for those in the fourth quartile compared with the lowest group (P=0.005 and P<0.001, respectively).
The best clinical threshold to predict death, MI, or stent thrombosis with the VerifyNow assay appeared to be 230 PRU (P<0.001). It was associated with:
- 2.10-fold elevated risk of the composite primary endpoint (P<0.0001)
- 66% elevated risk of death (P=0.04)
- 2.04-fold elevated risk of MI (P<0.001)
- 3.11-fold elevated risk of stent thrombosis (P=0.002)
Using this threshold improved risk classification for a net 23% of patients (P<0.001).
The only subgroup analysis that didn't turn up a significantly worse outcome with higher residual platelet reactivity was in diabetes patients, for whom the 30% elevated risk was not statistically significant at P=0.32.
Brar's group cautioned that their meta-analysis lacked data on CYP2C19 genotype and bleeding complications.
Brar reported having received speakers' bureau fees from and consulting for Accumetrics.
Wiviott reported having received research funding from Eli Lilly, Daiichi Sankyo, Pfizer, and Merck; consulting income from AstraZeneca, Bristol-Myers Squibb, sanofi-aventis, Ortho-McNeil, and Medco; and independent continuing medical education speaking with grants from Eli Lilly, Schering-Plough, Medtronic, and Daiichi Sankyo.
Hochholzer reported receiving consulting income from sanofi-aventis.