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

Circ Cardiovasc Interv. 2009 Dec;2(6):503-12. doi: 10.1161/CIRCINTERVENTIONS.109.879312. Epub 2009 Nov 17.

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%, 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-A 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects*
  • Angioplasty, Balloon, Coronary / mortality
  • Aspirin / therapeutic use
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Clopidogrel
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / complications*
  • Inflammation Mediators / blood*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Myocardial Infarction / immunology
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control*
  • Patient Selection
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Predictive Value of Tests
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Proportional Hazards Models
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Assessment
  • Stroke / immunology
  • Stroke / mortality
  • Stroke / prevention & control*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome
  • United States
  • Up-Regulation

Substances

  • Biomarkers
  • Inflammation Mediators
  • Platelet Aggregation Inhibitors
  • C-Reactive Protein
  • Clopidogrel
  • Pregnancy-Associated Plasma Protein-A
  • Ticlopidine
  • Aspirin