title: Vitamin D levels and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.
abstract: Suboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCIs). However, very few are known so far on the predictors of high-residual platelet reactivity (HRPR) despite antiplatelet strategies. Increasing attention has been paid in the last years to the role of vitamin D in atherothrombosis. Therefore, the aim of our study was to evaluate the impact of vitamin D levels on platelet function in patients treated with dual antiplatelet therapy (DAPT). Patients treated with DAPT (ASA and clopidogrel or ticagrelor) after a recent acute coronary syndrome (ACS) or elective PCI were scheduled for platelet function assessment at 30-90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®-Roche Diagnostics AG), HRPR was considered for ASPI test values > 862 AU*min (for ASA) and adenosine diphosphate (ADP) test values ≥417 AU*min (for ADP-antagonists). Fasting samples were obtained for main chemistry parameters and vitamin D level assessment. Our population is represented by 503 patients, who were divided according to vitamin D quartiles (≤9.1; 9.2-14.4; 14.5-21.7; >21.7 ng/ml). Lower vitamin D levels related with age (p = 0.04), diabetic status (p = 0.05), and previous coronary surgery (p = 0.007), therapy with beta-blockers and statins (p = 0.01 and p = 0.02). Vitamin D inversely related to the levels of total cholesterol (p = 0.01), triglycerides (p < 0.001), hemoglobin (p = 0.05), and HbA1c (p < 0.001). Significantly higher platelet reactivity was observed after platelet stimulation with ADP (p = 0.01), but not with other platelet activators. The prevalence of HRPR for ASA was low (1.2%) and not conditioned by Vitamin D levels (adjusted OR[95%CI] = 1.56[0.71-3.5], p = 0.27). HRPR with ADP-antagonists was observed in 26% of patients, and the rate increased with lower vitamin D quartiles (37.3% vs 22.2% vs 24.4% vs 20.2%, p = 0.005, adjusted OR[95%CI] = 1.23[1.02-1.49], p = 0.04). An absolute increase in HRPR with lower vitamin D levels was similarly observed among patients receiving ticagrelor (adjusted OR[95% CI] = 1.40[0.95-2.06], p = 0.08), and those on clopidogrel (adjusted OR[95%CI] = 1.31[0.99-1.75], p = 0.06). Thus, lower vitamin D levels are associated with higher platelet reactivity and impaired effectiveness of ADP-antagonists, while not influencing the effectiveness of ASA. Future studies will tell whether vitamin D supplementation can reduce platelet reactivity, overcoming the phenomenon of resistance to antiplatelet agents.
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: b Clinical Chemistry , Ospedale "Maggiore della Carità", Eastern Piedmont University , Novara , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pergolini
authors.affiliation: b Clinical Chemistry , Ospedale "Maggiore della Carità", Eastern Piedmont University , Novara , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rolla
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sartori
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Nardin
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Alon
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Daffara
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marino
authors.affiliation: b Clinical Chemistry , Ospedale "Maggiore della Carità", Eastern Piedmont University , Novara , Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: c Department of Cardiology , UMC St Radboud , Njimegen , The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: a Department of Cardiology , Ospedale "Maggiore della Carità",Eastern Piedmont University , Novara , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000077144:Clopidogrel; D015897:Comorbidity; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014807:Vitamin D / Q000097:blood*
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D014807:Vitamin D; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Clopidogrel; coronary artery disease; dual antiplatelet therapy; platelet aggregation; ticagrelor; vitamin D