Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta‐analysis

Abstract

To cite this article: Siller-Matula JM, Jilma B, Schrö r K, Christ G, Huber K. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J Thromb Haemost 2010; 8: 2624-41.Summary. To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel. Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction (MI), stent thrombosis, death and gastrointestinal bleeding. Studies included were randomized trials or post-hoc analyzes of randomized trials and observational studies reporting adjusted effect estimates. Twenty five studies met the selection criteria and included 159 138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events [risk ratio (RR) = 1.29, 95% confidence intervals (CI) = 1.15-1.45] and a 31% increased risk of MI (RR = 1.31, 95%CI = 1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR = 1.04, 95%CI = 0.93-1.16), whereas the risk of developing a gastrointestinal bleed under PPI treatment decreased by 50% (RR = 0.50, 95% CI = 0.37-0.69). The presence of significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk of developing an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure. In conclusion, concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction does not seem to be a class effect.

Platelet‐reactivity tests identify patients at risk of secondary cardiovascular events: a systematic review and meta‐analysis

“…Studies have shown that high on-treatment platelet reactivity (HPR) is a risk factor for secondary CVEs in patients receiving aspirin and/or clopidogrel treatment [7,8]. Suggested causes of the impaired efficacy of APT are non-compliance, APT intolerance, high platelet turnover, and nonresponse [9][10][11][12].…”

Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Coronary Stenting

“…79 A recent meta-analysis also showed a modest increase in MI but not death. 80 The COGENT (A Prospective, Randomized, Placebo-Controlled Trial of Omeprazole in Patients Receiving Aspirin and Clopidogrel Trial) trial, the only prospective randomized, double-blind comparison of omeprazole versus placebo in patients on aspirin and clopidogrel, showed reduced upper GI bleeding by more than 80% without a significant difference in cardiovascular outcomes. 81 Although there was no apparent cardiovascular interaction between clopidogrel and omeprazole, the trial was not sufficiently powered and thus the results of COGENT cannot rule out a clinically meaningful difference in cardiovascular events due to use of a PPI.…”

Antiplatelet Therapy and Proton Pump Inhibition

“…Interestingly, 2 recent meta-analyses of published studies found no association between PPI use and mortality. 32,33 A significant association with cardiovascular events was found in observational studies but not in those using propensity matching or participants of randomized trials. The presence of significant heterogeneity again indicates the biased and confounded nature of the evidence.…”