Relationship between baseline inflammatory markers, antiplatelet therapy, and adverse cardiac events after percutaneous coronary intervention: An analysis from the clopidogrel for the reduction of events during observation trial

Background - We evaluated patients undergoing percutaneous coronary intervention to assess the predictive value of high-sensitivity C-reactive protein (hs-CRP) and pregnancy-associated plasma protein-A (PAPP-A) on adverse cardiac outcomes and the effect of antiplatelet therapy on these outcomes. Methods and Results - Baseline blood samples were available on 1468 CREDO (Clopidogrel for the Reduction of Events During Observation) patients for hs-CRP testing and 1096 patients for PAPP-A testing. The 1-year primary end point was the composite incidence of death, myocardial infarction, or stroke. Patients in the highest 2 tertiles of hs-CRP had more events compared with the lowest tertile (11.4% versus 6.4%, P=0.003). Treatment with clopidogrel reduced the 1-year composite end point for patients in the highest 2 tertiles of hs-CRP (9.1% clopidogrel versus 13.5% placebo, P=0.04) but not in the lowest tertile. Elevated PAPP-A levels were associated with a trend toward more events at 1 year that did not reach statistical significance. Patients in the highest 2 tertiles of PAPP- randomized to clopidogrel had fewer events (7.3% clopidogrel versus 13.1% placebo, P=0.01), but no benefit was seen in the lowest tertile. A 46% risk reduction with randomization to clopidogrel was seen in patients in the highest 2 tertiles of both biomarkers (8.7% versus 16.2%, P=0.02). Conclusions - Patients undergoing nonurgent percutaneous coronary intervention who have elevated hs-CRP and PAPP-A have an increased incidence of adverse cardiovascular events. The clinical benefit of adding clopidogrel to aspirin seems greater in those with increased levels of these inflammatory biomarkers.