Background Platelet inhibition is important for patients with coronary artery disease. When dual antiplatelet therapy (DAPT) is required, a P2Y 12 -antagonist is usually recommended in addition to standard aspirin therapy. The most used P2Y 12 -antagonists are clopidogrel, prasugrel and ticagrelor. Despite DAPT, some patients experience adverse cardiovascular events, and insufficient platelet inhibition has been suggested as a possible cause. In the present review we have performed a literature search on prevalence, mechanisms and clinical implications of resistance to P2Y 12 inhibitors. Methods The PubMed database was searched for relevant papers and 11 meta-analyses were included. P2Y 12 resistance is measured by stimulating platelets with ADP ex vivo and the most used assays are vasodilator stimulated phosphoprotein (VASP), Multiplate, VerifyNow (VN) and light transmission aggregometry (LTA). Discussion/conclusion The frequency of high platelet reactivity (HPR) during clopidogrel therapy is predicted to be 30%. Genetic polymorphisms and drug-drug interactions are discussed to explain a significant part of this inter-individual variation. HPR during prasugrel and ticagrelor treatment is estimated to be 3–15% and 0–3%, respectively. This lower frequency is explained by less complicated and more efficient generation of the active metabolite compared to clopidogrel. Meta-analyses do show a positive effect of adjusting standard clopidogrel treatment based on platelet function testing. Despite this, personalized therapy is not recommended because no large-scale RCT have shown any clinical benefit. For patients on prasugrel and ticagrelor, platelet function testing is not recommended due to low occurrence of HPR.

BackgroundThe mechanisms behind residual platelet reactivity (RPR) despite aspirin treatment are not established. It has been shown that coronary artery disease (CAD) patients with high on-aspirin RPR have elevated levels of von Willebrand factor (vWF). ADAMTS13 is a metalloprotease cleaving ultra large vWF multimers into less active fragments.Our aim was to investigate whether ADAMTS13 and vWF/ADAMTS13 ratio were associated with high RPR, and further with clinical endpoints after 2 years.MethodsStable aspirin-treated CAD patients (n = 999) from the ASCET trial. RPR was assessed by PFA-100. ADAMTS13 antigen and activity were analysed using chromogenic assays. Endpoints were a composite of acute myocardial infarction, stroke and death.ResultsThe number of patients with high RPR was 258 (25.8%). Their serum thromboxane B2 (TxB2) levels were low, indicating inhibition of COX-1. They had significantly lower levels of ADAMTS13 antigen compared to patients with low RPR (517 vs 544 ng/mL, p = 0.001) and significantly lower ADAMTS13 activity (0.99 vs 1.04 IU/mL, p = 0.020). The differences were more pronounced when relating RPR to ratios of vWF/ADAMTS13 antigen and vWF/ADAMTS13 activity (p < 0.001, both). We found an inverse correlation between vWF and ADAMTS13 antigen (r = −0.14, p < 0.001) and ADAMTS13 activity (r = −0.11, p < 0.001). No correlations between TxB2 and ADAMTS13 antigen or activity, were observed, implying that ADAMTS13 is not involved in TxB2 production. Patients who experienced endpoints (n = 73) had higher vWF level (113 vs 105%, p = 0.032) and vWF/ADAMTS13 antigen ratio (0.23 vs 0.20, p = 0.012) compared to patients without. When dichotomizing vWF/ADAMTS13 antigen at median level we observed that patients above median had higher risk for suffering endpoints, with an adjusted OR of 1.86 (95% CI 1.45, 2.82).ConclusionThese results indicate that ADAMTS13 is of importance for RPR, and that it in combination with vWF also is associated with clinical endpoints in stable CAD patients on aspirin.Trial registrationClinicaltrials.gov NCT00222261. Registered 13.09.2005. Retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s12959-017-0151-3) contains supplementary material, which is available to authorized users.

Introduction ADAMTS13 cleaves von Willebrand Factor (VWF) into less active fragments. TSP1 binds to VWFs cleavage-site, protecting it from degradation. Low ADAMTS13 and high VWF have been associated with cardiovascular disease (CVD) and atrial fibrillation (AF). We aimed to investigate the interplay between VWF, ADAMTS13 and TSP1, and assess any relation to endpoints. Materials and methods 1027 elderly with a recent myocardial infarction (MI) were followed for 2 years. ADAMTS13 antigen (ag) and activity (act), VWF ag and TSP1 were analyzed. The primary endpoint (MACE; n = 210) included MI, stroke, heart failure hospitalization, coronary revascularization and death. The secondary endpoint was new-onset AF (n = 43). Results ADAMTS13 ag and act were weakly correlated to VWF (r = 0.10, P = 0.002, both). TSP1 did not correlate to ADAMTS13 or VWF. Patients experiencing a MACE had higher VWF and lower ADAMTS13(ag) at baseline (P &lt; 0.012, both), however not significant after adjusting for covariates. The association with MACE was mainly driven by death (n = 40), with an adjusted OR 2.4 (P = 0.008) for VWF Q4 vs. Q1-3 and OR 0.4 (P = 0.012) for ADAMTS13(ag) Q1 vs. Q2-4. VWF was lower (1.25 vs. 1.39 IU/mL, P = 0.008) and VWF/ADAMTS13(ag)-ratio was lower (1.81 vs. 2.05 x10−3, P = 0.009) in patients with new-onset AF, and these associations persisted in adjusted models. Conclusion In elderly patients with a recent MI, levels of VWF, ADAMTS13 and TSP1 did not correlate. ADAMTS13 and VWF associated weakly with MACE, mainly driven by death. Low VWF and VWF/ADAMTS13-ratio were associated with new-onset AF in our population and needs further research.