title: Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy.
abstract: BACKGROUND
  Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition.
  
  
  METHODS
  We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2Y12 assay at the maintenance outpatient setting.
  
  
  RESULTS
  Concomitant SRN (n=266) significantly (p=0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9PRU) when compared (232.1 ± 73.5PRU) to the SRN-free (n=192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk=1.675; Odds ratio [1.059-2.648]; p=0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT.
  
  
  CONCLUSIONS
  The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study.
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea; Department of Pulmonology and Critical Care Medicine, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea; Clinical Trial Center, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea. Electronic address: kimmh@dau.ac.kr.
authors.forename: Moo Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Clinical Trial Center, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Long Zhe
authors.initials: LZ
authors.lastname: Guo
authors.affiliation: Clinical Trial Center, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Cai
authors.initials: C
authors.lastname: De Jin
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Young Rak
authors.initials: YR
authors.lastname: Cho
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Kyungil
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Cardiology, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Park
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Serebruany
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000503:physiopathology / Q000601:surgery*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage*; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010979:Platelet Function Tests; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009566:Nitrates; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Adverse events; Clinical outcomes; Clopidogrel; Dual anti-platelet therapy; Nitrates; Platelet reactivity