Prolonged use of dual antiplatelet
therapy (
DAPT) post-
percutaneous coronary intervention (PCI) has been shown to reduce the risk of major adverse cardiovascular events (
MACE), but with increased
bleeding. It remains unknown whether
biomarkers of platelet activation may be useful for identifying patients at increased risk of
MACE. The
DAPT study was a randomized trial of 12 versus 30 months of
DAPT in patients who underwent PCI. Serum
biomarkers [myeloid-related
protein (MRP)-8/14,
P-selectin, soluble CD-40
ligand (sCD40L)] were assessed in 1399 patients early post-PCI. On-treatment platelet reactivity index (PRI) using VASP phosphorylation was assessed in 443 patients randomized to continued
DAPT at 1 year.
MACE was defined as CV death, MI, or
ischemic stroke. Multivariable models were adjusted for baseline characteristics, index event, and
stent type. A stepwise increase in the risk of
MACE was observed with increasing tertiles of both MRP-8/14 and
P-selectin (p-trend = 0.04 for both). After multivariable adjustment, the adjusted HR (95% CI) for
MACE in patients in the top tertile was 1.94 (1.14-3.30) for MRP-8/14 and 1.62 (0.99-2.64) for
P-selectin. In contrast, baseline sCD40L was not associated with CV risk. Among patients randomized to continued
DAPT, higher on-treatment platelet reactivity was not significantly associated with risk of
MACE (p-trend = 0.32; adj-HR T3 vs. T1 1.54, 95% CI 0.20-12.18) or
bleeding (P-trend = 0.17; adj-HR 0.25, 95% CI 0.05-1.21). MRP-8/14 and soluble
P-selectin may be useful for identifying patients at increased risk of
MACE after PCI. The utility of on-treatment platelet function testing requires further study.Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier NCT00977938.