ABSTRACT
BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine. OBJECTIVES: Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine. METHODS: We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA). RESULTS: We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04). CONCLUSIONS: Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel. CLINICAL TRIAL REGISTRATION: NCT01896557.
Subject(s)
Coronary Artery Disease/drug therapy , Drug Interactions , Omeprazole/therapeutic use , Ranitidine/therapeutic use , Ticlopidine/analogs & derivatives , Aged , Blood Platelets/drug effects , Clopidogrel , Double-Blind Method , Drug Therapy, Combination/methods , Female , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function Tests/methods , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Ticlopidine/therapeutic useABSTRACT
The long-term behavior of endothelial markers was studied in patients with Eisenmenger syndrome who were subjected to conventional therapy (no vasodilators) and observed for 18 months. Biochemical markers were analyzed comparatively in patients with class II or III symptoms (group 1, n=10) and patients with class IV symptoms (group 2, n=7). Plasma von Willebrand factor antigen (vWF:Ag), thrombomodulin, tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1), and D-dimer were determined by immunoenzymatic assay at baseline, and at 6, 12, and 18 months. At baseline, the main clinical difference between groups was a decreased peripheral oxygen saturation in group 2 versus group 1 (77+/-5% and 86+/-4%, respectively, p=0.001). Basal vWF:Ag and t-PA were increased and thrombomodulin was decreased in both groups in comparison with controls (p<0.0001), while D-dimer was increased in group 2 only (p=0.0003). In response to treatment, there was a decrease in vWF:Ag in both groups (19% and 23%, respectively in groups 1 and 2, at 18 months vs. baseline, p<0.0001) and t-PA in group 1 (38% vs. baseline, p=0.0485). Plasma vWF:Ag tended to be higher in group 2 in comparison with group 1 during the whole follow-up. Levels of PAI-1 greater than 38.4 ng/mL (upper 90% limit for normals) and D-dimer greater than 500 ng/mL were detected in individual patients (both groups) during the follow-up period. Thrombomodulin remained decreased in both groups. Thus, severity of symptoms in the Eisenmenger syndrome appears to correlate with low oxygen saturation and higher vWF:Ag levels. Improvement of endothelial dysfunction may occur in response to treatment, although increased risk for thrombosis persists, in view of residual abnormalities.
