title: Cigarette Smoking Does Not Enhance Clopidogrel Responsiveness After Adjusting VerifyNow P2Y12 Reaction Unit for the Influence of Hemoglobin Level.
abstract: The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU).
  
  
  
  PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity.
  
  
  
  Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU.
  
  
  
  A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813).
  
  
  
  The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea; Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Yun Gi
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea. Electronic address: dasome2@snu.ac.kr.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Suh
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: Si-Hyuck
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Park
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Yoon
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Youn
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Chae
authors.affiliation: Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Cardiovascular Center & Department of Internal Medicine, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D054855:Drug-Eluting Stents; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: cigarette smoking; clopidogrel; hemoglobin; platelet reactivity