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.


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.
Dosh
Kristofer
K
Department of Internal Medicine/Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY 40536-0200, USA. kmdosh2@email.uky.edu
Berger
Peter B
PB
Marso
Steven
S
van Lente
Fredrick
F
Brennan
Danielle M
DM
Charnigo
Richard
R
Topol
Eric J
EJ
Steinhubl
Steven
S
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000401:mortality; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D018836:Inflammation Mediators / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D020521:Stroke / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D015854:Up-Regulation
D015415:Biomarkers; D018836:Inflammation Mediators; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D011266:Pregnancy-Associated Plasma Protein-A; D013988:Ticlopidine; D001241:Aspirin