Relationship Between Baseline Inflammatory Markers, Antiplatelet Therapy, and Adverse Cardiac Events After Percutaneous Coronary Intervention

Abstract

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%, Pϭ0.003). 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, Pϭ0.04) 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-A randomized to clopidogrel had fewer events (7.3% clopidogrel versus 13.1% placebo, Pϭ0.01), 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%, Pϭ0.02). Conclusions-Patients

High Sensitivity C-Reactive Protein and Outcomes Following Percutaneous Coronary Intervention in Contemporary Practice

“…However, the introduction of DES, longer duration of dual antiplatelet therapy, and greater awareness of the risk of stent thrombosis have led to many changes in PCI practice, which may have impacted the putative relationship between inflammation and outcomes. 46 Indeed, in the present study, there was no relationship between delta hsCRP and mortality and a weak univariate relationship with the combined end point of death or MI. Higher preprocedural and postprocedural hsCRP levels were associated with a 2-to 3-fold greater unadjusted rate of death and the combined end point of death or MI over a 5-year period; representing the longest follow-up to date among studies exploring the impact of inflammation in PCI adjustment for clinical covariates, however, no independent relationship with mortality was present for either preor post-PCI hsCRP levels.…”

A Point-of-Care Platelet Function Assay and C-Reactive Protein for Prediction of Major Cardiovascular Events After Drug-Eluting Stent Implantation

“…Interestingly, on the basis of the observed differences of outcomes according to platelet reactivity in patients with elevated CRP levels, one might pose the hypothesis that elevated CRP could indicate a higher-risk population who may benefit from a selective platelet function test or tailoring antiplatelet therapy. Similarly, in the CREDO (Clopidogrel for the Reduction of Events During Observation) trial, patients with elevated CRP had increased atherothrombotic events, and the clinical benefit of clopidogrel seems greater in those with elevated CRP, but not lower CRP (21). A similar proof of concept was also documented in a large clinical trial with statin treatment (22).…”

Genetic Determined Low Response to Thienopyridines is Associated with Higher Systemic Inflammation in Smokers

“…For instance, VASP PRI >50% has been suggested as a definition of high on-treatment platelet reactivity in post-PCI patients [2]. Additionally, the ability of clopidogrel and prasugrel in the reduction of inflammation would be particularly important in the clinical setting since it has been demonstrated that post-PCI inflammatory response is the primary causative mechanism of ISR [8,9,18], and that elevated inflammatory markers, particularly CRP [19], is associated with an increased incidence of adverse cardiac events in post-PCI patients [20]. For instance, it has been demonstrated that CRP values >2.5 mg/l at 30 days after PCI is associated with long term (at 12 month) adverse clinical events, particularly ISR [21].…”