title: Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity. The result of the ACCEL-DIP Study.
abstract: Adjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: -2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.
authors.forename: Y
authors.initials: Y
authors.lastname: Park
authors.affiliation: Dr. Young-Hoon Jeong, Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital and, Gyeongsang National University School of Medicine, 79 Gangnam-ro, Jinju, Gyeongsangnam-do, 660-702, Korea, Tel.: +82 55 750 8873, Fax: +82 55 750 8873, E-mail: goodoctor@naver.com.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Jeong
authors.forename: U S
authors.initials: US
authors.lastname: Tantry
authors.forename: J H
authors.initials: JH
authors.lastname: Ahn
authors.forename: K H
authors.initials: KH
authors.lastname: Kim
authors.forename: J-S
authors.initials: JS
authors.lastname: Koh
authors.forename: J-R
authors.initials: JR
authors.lastname: Park
authors.forename: S-J
authors.initials: SJ
authors.lastname: Hwang
authors.forename: C H
authors.initials: CH
authors.lastname: Kwak
authors.forename: J-Y
authors.initials: JY
authors.lastname: Hwang
authors.forename: P A
authors.initials: PA
authors.lastname: Gurbel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004176:Dipyridamole / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010750:Phosphoproteins / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D056910:Republic of Korea; D015607:Stents; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D058986:Phosphodiesterase 5 Inhibitors; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D004176:Dipyridamole; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D013988:Ticlopidine; D001241:Aspirin
keywords: Platelets; clopidogrel; dipyridamole; intervention