Proton pump inhibitors and clopidogrel: an association to avoid?

Abstract

Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events following an acute coronary syndrome or stent implantation, but the associated increased risk of gastro-intestinal bleeding often leads to the co-administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease antiplatelet effects of clopidogrel ex vivo, raising concerns about the cardiovascular safety of this drug combination. Clinical trials investigating PPI-clopidogrel interactions have provided conflicting results and are all subject to methodological critiques. The much desired and much needed prospective, double-bind, randomized, placebo-controlled trials with adequate follow-up and sample size have not yet been performed. Indeed, the Clopidogrel and the Optimization of GI Events Trial, which would have had such characteristics, was stopped prematurely. As a consequence, the question of the PPI-clopidogrel interaction is still unresolved, and clinical consequences cannot be excluded. At this time such combination therapy should, therefore, be provisionally advocated only for patients at high risk of bleeding (prior upper gastro-intestinal bleeding, advanced age, concomitant use of warfarin, steroidal or non-steroidal anti-inflammatory drugs and Helicobacter pylori infection) and avoiding PPIs with strong affinity for cytochrome CYP2C19, such as omeprazole and esomeprazole.

Continuous improvement on the rationality of prophylactic injectable PPIs usage by a clinical pharmacist-led guidance team at a Chinese tertiary teaching hospital

“…Third, although rational PIPU increased significantly during the intervention phase, the sample size was small in this study. Additionally, the combination of clopidogrel and omeprazole or esomeprazole should be avoided; 36 , 37 several cases of inappropriate use were found before and after the PDCA cycles in our study. Therefore, larger sample sizes and further pharmacoeconomic analyses are warranted, to better quantify the outcomes.…”

Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review

“…The authors note that the studies in their review were observational; therefore, causation is hard to pinpoint because the studies were not randomized. Another review of the literature in 2014 came to the same conclusion [ 81 ]. In the analyzed trials, a lower efficacy with the concurrent use of a PPI and clopidogrel was detected; however, the studies were observational and no obvious causality was identified.…”

“…In the analyzed trials, a lower efficacy with the concurrent use of a PPI and clopidogrel was detected; however, the studies were observational and no obvious causality was identified. Earlier reviews have noted that, due to CYP interactions, it is felt that PPIs decrease blood levels of clopidogrel due to the increase in its metabolism, but make no mention of how the observational, nonrandomized nature of the studies could make these studies not as valid as the authors would have hoped [ 81 ]. Co-prescribing these two drugs seems appropriate to protect people who need clopidogrel's protection.…”

Treatment effects of Shilajit on aspirin‐induced gastric lesions in rats

“…Another finding of this study was that the blood glucose level decreased in the Shilajit control group compared to other groups, indicating the hypoglycemic and anti‐diabetic properties of the Shilajit extract (Gupta, 1966; Talbert, 2004). Omeprazole has been suggested to be involved in cholesterol metabolism (D’Ugo et al, 2014). Similarly, Shilajit has been shown to reduce triglyceride and LDL cholesterol levels and increase HDL cholesterol levels (Sharma et al, 2011).…”