Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention

Gupta, Ekta; Olden, Kevin W.

doi:10.14309/00000434-200910003-01103

Cited by 15 publications

(22 citation statements)

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“…1). One prospective randomized trial [23], two post-hoc analyses of randomized trials [11,24], 20 retrospective data analyses of cohort studies [13][14][15]18,21,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and two case-control studies [18,43] included 159 138 patients (54 689 with PPIs and 104 449 without). Six studies were excluded: five studies without adjusted effect estimates and one study including the same patient population as another included study [16,17,19,22,44,45].…”

Section: Resultsmentioning

confidence: 99%

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

Siller‐Matula

Jilma

Schrör

et al. 2010

Journal of Thrombosis and Haemostasis

121

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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.

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Section: Resultsmentioning

confidence: 99%

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

Siller‐Matula

Jilma

Schrör

et al. 2010

Journal of Thrombosis and Haemostasis

121

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“…54 Gupta et al followed up 315 patients post-PCI on clopidogrel and PPI for 50 months and found that the major adverse cardiovascular event rate was 56% vs 38% in the clopidogrel alone group (P = 0.025). 55 This was echoed by two recent trials revealing an increase in cardiovascular events in patients taking PPI and clopidogrel. 56,57 The latest trial by van Boxel et al identified 18 139 new clopidogrel users with 5734 patients using PPI concurrently and found that the co-therapy was associated with an increase risk of myocardial infarction (HR 1.93, 95% CI 1.40-2.65) and unstable angina (HR 1.79, 95% CI 1.60-2.03).…”

Section: Controversies Of Ppi Plus Clopidogrel Clinical Outcome Studiesmentioning

confidence: 98%

“…Higher death rate and rehospitalization Pezalla et al 52 Retrospective cohort 1 000 MI (1 year) Higher rate of MI Aubert et al 53 Retrospective 14 383 Cardiovascular events Increased risk of cardiovascular events Wang et al 54 Retrospective 98 Re-infarction Higher risk of re-infarction Gupta et al 55 Retrospective 315 MI, death, target vessel failure Higher risk of major adverse cardiovascular events Tsai et al 56 Retrospective 3 580 Cardiovascular events Increase risk Gaglia et al 57 820 Major adverse cardiac events Greater risk of MACE Van Boxel et al 58 Retrospective and found no differences in the rate of myocardial infarction, death and revascularization at 1 year between those treated with concomitant clopidogrel with and without a PPI. 59 Simon et al studied 2208 patients and found no evidence of major cardiovascular outcomes with PPI co-therapy.…”

Section: Attenuation Of Antiplatelet Effectsmentioning

confidence: 99%

Controversy of proton pump inhibitor and clopidogrel interaction: A review

Tan

2010

J of Digest Diseases

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A proton pump inhibitor (PPI) is often co-prescribed with clopidogrel to reduce the gastrointestinal risk of bleeding ulcers in patients following acute coronary syndrome or a stent implant. However, the safety issue of such practice has been scrutinized after some studies reporting an increased incidence of cardiovascular events and mortality, although there have also been contrary research reports. This has lead to a warning statement from the US Food and Drug Administration cautioning the concomitant use of PPI and clopidogrel. This review examines the evidence of PPI as gastroprotective agent, histamine H(2) antagonists as an alternative therapy, the influence of PPI on the antiplatelet effect of clopidogrel, and the controversies of various studies.

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“…Risk factors for non-response to antiplatelet therapy include advanced age, 59 type 2 diabetes, 60 particularly if treated with insulin, 61 overweight patients, 62 genetic factors 49,[63][64][65][66] and concomitant medications, particularly proton pump inhibitors. 67,68 The Concept of a Therapeutic Window for Antiplatelet Therapy…”

Section: Perspectivesmentioning

confidence: 99%

Current Concepts in the Clinical Utility of Platelet Reactivity Testing

Jean-Philippe¹

2013

Interventional Cardiology Review

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The pharmacodynamic effect of clopidogrel varies among individuals; approximately a third will have high on-treatment platelet reactivity (HTPR) to adenosine diphosphate and may benefit from more intensive antiplatelet therapy. Platelet reactivity testing has an important role in monitoring the therapeutic efficiency of clopidogrel and the safety of more potent drugs that confer an increased bleeding risk, because it provides a direct measure of the biological effect of these drugs. Numerous studies have demonstrated an association between HTPR and the risk of cardiac events in acute coronary syndrome (ACS) or after percutaneous coronary intervention (PCI). While the prognostic value of platelet reactivity testing following PCI has been demonstrated repeatedly in cohort studies and meta-analyses, randomised controlled studies investigating the clinical utility of the technique to guide treatment decisions failed to improve clinical outcomes of clopidogrel-treated patients undergoing stent implantation. Available data suggest that platelet function monitoring may be carried out in clopidogrel-treated patients with a higher risk of thrombotic events. These include patient risk factors such as body mass index (BMI), type 2 diabetes, and those prior unexpected ischemic events such as stent thrombosis, as well as procedural risk factors. As we move towards conclusively defining a therapeutic window associated with both cardiovascular (upper threshold) and bleeding risk (lower threshold) for antiplatelet agents, platelet reactivity testing will become a central tool in the practice of personalised strategies.

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Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention

Cited by 15 publications

References 0 publications

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

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

Controversy of proton pump inhibitor and clopidogrel interaction: A review

Current Concepts in the Clinical Utility of Platelet Reactivity Testing

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