Efficacy and safety of clopidogrel only vs. clopidogrel added proton pump inhibitors in the treatment of patients with coronary heart disease after percutaneous coronary intervention

Abstract

Background Controversy still exists that whether clopidogrel should add proton pump inhibitors (PPIs) in patients with coronary heart disease after percutaneous coronary intervention (PCI). The aim of this study was to evaluate the efficacy and safety of clopidogrel added proton pump inhibitors (PPIs) vs. clopidogrel for the treatment of patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods and results We systematically searched PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library for all clinical trials that were published on this topic through October 2018. We specifically selected the clinical trials that evaluated the efficacy and safety of clopidogrel added proton pump inhibitors vs. clopidogrel in the treatment of patients with coronary heart disease after PCI. RevMan 5.0 software was used for quantitative data analyses. 15 randomized controlled trials including 50,366 patients were included. The meta-analysis results showed that compared with the clopidogrel added PPI group, the non-PPI group had significantly less risk of MACE[RR = 0.82,95%CI:0.77–0.88], myocardial infarction recurrence[RR = 0.72,95%CI:0.57–0.90], stent thrombosis[RR = 0.71,95%CI:0.56–0.92], Target vessel revascularization (TVR)[RR = 0.77,95%CI:0.63–0.93] and stroke [RR = 0.72,95%CI:0.67–0.76]. The risks of all cause death [RR = 1.14,95%CI:0.85–1.51], cardiovascular death [RR = 1.14, 95% CI: 0.85–1.52], bleedings events [RR = 1.60,95%CI:0.53–4.81] were similar in the two groups. Conclusions The patients in the non-PPI group were observed to be associated with less risk of MACE, myocardial infarction recurrence, stent thrombosis, target vessel revascularization (TVR) and stroke. And the two groups had similar all cause death, cardiovascular death, bleedings events.

Use of Clopidogrel and Proton Pump Inhibitors Alone or in Combinations in Persons with Diabetes in Denmark; Potential for CYP2C19 Genotype-Guided Drug Therapy

“…Clopidogrel is associated with increasing risks of gastrointestinal (GI) bleeding both when given alone or in combination with aspirin [ 4 , 20 ]. Consequently, clopidogrel is commonly prescribed in combinations with PPIs to prevent GI bleeding [ 4 , 7 , 20 , 21 ].…”

“…Clopidogrel is associated with increasing risks of gastrointestinal (GI) bleeding both when given alone or in combination with aspirin [ 4 , 20 ]. Consequently, clopidogrel is commonly prescribed in combinations with PPIs to prevent GI bleeding [ 4 , 7 , 20 , 21 ]. According to Flockhart and others, the PPIs are inhibitors of CYP2C19 with esomeprazole reported as a strong inhibitor and pantoprazole, lansoprazole and omeprazole as weaker inhibitors [ 12 , 21 , 22 ].…”

“…Inconsistent effects on cardiovascular outcomes of concomitant use of clopidogrel and PPIs have been reported [ 27 , 28 ]. However, clinically important interactions cannot be excluded as substantiated in several literature studies and meta-analysis showing that the combined use of clopidogrel and PPIs are associated with increased adverse cardiovascular events, such as major adverse cardiac events (MACE), stent thrombosis (ST) and myocardial infarction (MI) following PCI [ 20 , 24 , 29 , 30 ]. The concomitant use of clopidogrel and PPIs exhibit the Achilles’ heel of personalized medicine, referred to as phenoconversion, which describes the overlapping of DDI and DGI [ 31 , 32 ], also denoted to as drug–drug–gene interaction (DDGI).…”

Binding of omeprazole to protein targets identified by monoclonal antibodies

“…Omeprazole and other PPIs have come under increased scrutiny because they are pervasively prescribed and used, frequently at doses that are higher than required to inhibit acid secretion and for longer periods than are clinically indicated [ 10 – 13 ]. Furthermore, a series of investigations has linked PPI use to a number of conditions that include cardiovascular disease [ 14 ], osteoporosis [ 15 ], C. Difficile colitis [ 16 ], community acquired pneumonia [ 17 ], and dementia [ 18 – 20 ], though different groups have arrived at opposite conclusions [ 21 , 22 ]. The causal effect on these conditions has been debated, though a recent randomized control study suggested that only enteral infections were increased by pantoprazole administration within a three year follow-up period [ 23 ].…”

Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: insights from a single-centred retrospective study

“…19 In this case, lansoprazole and pantoprazole could be considered as a rational choice. 34 In terms of cost-effective prescribing, the DDC results showed that the highest average daily costs of PPIs were injectable omeprazole, followed by oral esomeprazole. Thus, the result indicated that these patients paid a higher price when these drugs were prescribed.…”