Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole

Abstract

This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole.One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10 mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30 mg daily, Group B: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30 mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events.A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05).In patients diagnosed with NSTE-ACS who have had drug-eluting stent implantation, simultaneously administering clopidogrel, atorvastatin, and lansoprazole did not decrease the antiplatelet efficacy of clopidogrel or increase adverse event frequency over 6 months.

Prophylactic use of acid suppressants in adult acutely ill hospitalised patients: A systematic review with meta‐analysis and trial sequential analysis

“…Three trials were adjudicated as having overall low risk of bias; the remaining trials were adjudicated as having an overall high risk of bias (Figure 2). Only six and eight trials were adjudicated as low risk of bias in the domains for ‘selective reporting’ and ‘allocation concealment’ respectively. More than 75% of the trials were at unclear or high risk of financial bias (‘other bias’ domain), mostly because there were no declarations about funding at all.…”

Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel

“…The baseline characteristics of the patients in the 4 RCTs [ 5 , 6 , 8 , 30 ] and 8 controlled observational studies [ 7 , 9 , 13 , 25 – 29 ] are shown in Table 3 . The study sample sizes ranged from 104 to 8582 patients.…”

“…All 12 articles [ 5 – 9 , 13 , 25 – 30 ] reported MACE as a primary endpoint. It occurred in 1580 of the 16,839 patients (9.38%) in the PPI group, and 1281 of 16,632 patients (7.70%) in the placebo group.…”

Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice

“…If an alternative PPI has to be considered, in vitro studies using human liver microsomes have confirmed that PPIs like rabeprazole, lansoprazole, dexlansoprazole, and pantoprazole do not show evidence of mechanism-based inhibition [29]. Clinical studies have also reported that effects of lansoprazole and pantoprazole on clopidogrel antiplatelet activity are not as potent as omeprazole [43][44][45]. When clopidogrel and PPI coadministration is necessary, switching to a PPI other than omeprazole or esomeprazole may be considered, in light of the evidence presented herein.…”