The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?

Sharma, Rakesh; Reddy, Hanumanth K.; Sharma, Rohit K.; Moazazi, Mathilde; Elango, Lovett; Singh, Vibhuti; Williams, David; Voelker, Donald J.

doi:10.2147/cpaa.s9807

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…Diabetes and African American race were strong predictive factors. Hyporesponsiveness to clopidogrel can be secondary to several factors, including age, body mass index, diabetes, dyslipidemia, chronic renal disease, genetic polymorphism, and pharmacokinetic and pharmacodynamic interactions arising from concomitant use of other drugs 23,24. Failure to take the drug as prescribed certainly can produce hyporesponsiveness.…”

Section: Discussionmentioning

confidence: 99%

Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

Sharma¹,

Erickson²,

Sharma³

et al. 2013

VHRM

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BackgroundA dual antiplatelet regimen has been shown to reduce the risk of major adverse cardiovascular events after percutaneous coronary intervention. However, there is little information available on inhibition of platelet aggregation in patients with a prior coronary stent presenting with chest pain. This study evaluated the prevalence of hyporesponsiveness to clopidogrel and factors associated with this in patients presenting to our emergency department with chest pain who had previously undergone coronary stent placement and were prescribed dual antiplatelet therapy.MethodsResponsiveness to clopidogrel was evaluated in a cohort of 533 consecutive stented patients presenting to the emergency department with chest pain. P2Y12 reaction units (PRU) and percent P2Y12 inhibition with clopidogrel were measured in all patients. Of 533 patients, 221 (41.6%) had PRU ≥ 230. A multivariate logistic regression model was used to determine the relationship between hyporesponsiveness to clopidogrel (defined as PRU ≥ 230) and several potential risk factors, ie, gender, age, race, type 1 or type 2 diabetes, hypertension, smoking, chronic renal failure, and obesity.ResultsThere was a greater risk of hyporesponsiveness in African Americans than in non-African American patients (adjusted odds ratio [OR] = 2.165), in patients with type 2 diabetes than in those without (adjusted OR = 2.109), and in women than in men (adjusted OR = 1.813), as well as a greater risk of hyporesponsiveness with increasing age (adjusted OR = 1.167 per decade).ConclusionThere was a high prevalence of hyporesponsiveness to clopidogrel in patients presenting with chest pain and a prior coronary stent. Non-insulin-dependent diabetes mellitus and African American race were the strongest predictors of hyporesponsiveness to clopidogrel, followed by gender and age.

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Section: Discussionmentioning

confidence: 99%

Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

Sharma¹,

Erickson²,

Sharma³

et al. 2013

VHRM

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“…Thus far, several researchers have discussed whether PPIs may attenuate the cardiovascular protection of clopidogrel for patients with acute coronary syndrome. [23][24][25][26] Additionally, the single use of PPIs also has potentially adverse clinical outcomes in high-risk cardiovascular populations.…”

Section: Ppis and Myocardial Infarctionmentioning

confidence: 99%

Potential Cardiovascular Risks of Proton Pump Inhibitors in the General Population

Zhu

Hong

2017

Int. Heart J.

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SummaryProton pump inhibitors (PPIs) are the most effective gastric acid-suppressing agents and the mainstay medical therapy for a series of acid peptic diseases. In general, the safety profile of PPIs is excellent. However, with long-term drug administration, the safety and potency of PPIs has been questioned. In the cardiovascular field, drug-drug interactions related to PPIs have been identified with particular attention regarding the use of PPIs combined with clopidogrel in patients with acute coronary syndrome. Currently, cardiovascular risks from PPIs may extend from patients with coronary artery disease to the general population. This review summarizes the possible cardiovascular risks in PPI users with no history of cardiovascular diseases and discusses possible biological mechanisms. (Int Heart J 2017; 58: 163-166)

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“…However, FDA warnings began a debate in the medical community that has often centered on the decreased efficacy of clopidogrel with concomitant use of PPIs. 56 …”

Section: Pfasmentioning

confidence: 99%

Evolving role of platelet function testing in coronary artery interventions

Sharma

Voelker²,

Sharma

et al. 2012

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The substantial reduction in ischemic events provided by the dual antiplatelet regimen with aspirin and clopidogrel is well documented in patients with acute coronary syndrome and patients undergoing percutaneous coronary intervention. Recently the variable response to the antiplatelet agents has received considerable attention after several “boxed warnings” on clopidogrel. This led to intense controversy on pharmacokinetic, pharmacodynamic, and pharmacogenomic issues of antiplatelet drugs, especially clopidogrel. Research use of platelet function testing has been successfully validated in identifying new antiplatelet drugs like prasugrel and ticagrelor. These platelet function assays are no longer regarded just as a laboratory phenomenon but rather as tools that have been shown to predict mortality in several clinical trials. It is believed that suboptimal response to an antiplatelet regimen (pharmacodynamic effect) may be associated with cardiovascular, cerebrovascular, and peripheral arterial events. There has been intense controversy about this variable response of antiplatelet drugs and the role of platelet function testing to guide antiplatelet therapy. While the importance of routine platelet function testing may be uncertain, it may be useful in high-risk patients such as those with diabetes mellitus, diffuse three vessels coronary artery disease, left main stenosis, diffuse atherosclerotic disease, and those with chronic renal failure undergoing percutaneous coronary intervention. It could also be useful in patients with suspected pharmacodynamic interaction with other drugs to assure the adequacy of platelet inhibition. While we wait for definitive trials, a predictive prognostic algorithm is necessary to individualize antiplatelet therapy with P2Y12 inhibitors based on platelet function assays and genetic testing.

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The interaction between clopidogrel and proton pump inhibitors (PPI): is there any clinical relevance?

Cited by 3 publications

References 41 publications

Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

Potential Cardiovascular Risks of Proton Pump Inhibitors in the General Population

Evolving role of platelet function testing in coronary artery interventions

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