A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

Background: The rapid rise in the availability and use of pharmaceutical agents, and particularly polypharmacy, directly increases the risk for patients to experience adverse drug reactions (ADRs). There are few studies on the overall incidence and costs of ADRs.Objective: The aim of this study was to estimate the incidence and costs of emergency department (ED) visits related to ADRs for patients greater than 65 years of age using administrative data, and to describe risk factors for experiencing severe ADRs.Methods: We employed a retrospective cohort design based on population-based healthcare administrative clinical databases. Identification of ADR-related ED visits from the administrative database was based on International Classification of Diseases, 10th Revision-Canadian Enhancement (ICD-10-CA) codes for each ED visit. The incidence and costs of ADR-related ED visits and subsequent hospital admissions were estimated for all adults aged 66 years and above for the period April 2003–March 2008. Costs were standardized and reported in 2008 Canadian dollars. Logistic regression was used to detect risk factors for severe ADRs.Results: Approximately 0.75% of total annual ED visits among adults aged 66 years and above were found to be ADR-related, and among these patients 21.6% were hospitalized. In 2007, the cost of ADR-related visits was $333 per ED visit and $7528 per hospitalization for a total annual cost of $13.6 million in Ontario, or an estimated $35.7 million in Canada. Severe ADRs were associated with sex, age, comorbid disease burden, multiple drugs, multiple pharmacies, newly prescribed drugs, recent ED visit, recent hospitalization and long-term care (LTC) residence.Conclusions: ADRs are an important public health issue that threaten the safety of drug therapy and results in significant economic burden to the healthcare system. ED visits related to ADRs may be underestimated in retrospective studies using administrative data compared with prospective studies. Further research is needed to better understand the risk of experiencing severe ADRs among LTC residents.

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“…The administrative datasets used in this study have been used extensively for research about prescription medications. [9–11]…”

Section: Methodsmentioning

confidence: 99%

Incidence and Economic Burden of Adverse Drug Reactions among Elderly Patients in Ontario Emergency Departments

2012

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“…Consequently, concomitant use of clopidogrel and PPIs, in particular omeprazole and esomeprazole, reduces clopidogrel active metabolite levels and ex vivo measured platelet inhibition [33,34]. Although some studies suggest that concomitant therapy with PPIs and clopidogrel is associated with an increased risk of cardiovascular events [18,35,36], a clinically meaningful effect of this interaction on cardiovascular outcomes has not been established [33]. However, since a clinical significant interaction cannot be completely excluded, Food and Drug Administration (FDA) recommends avoiding omeprazole and esomeprazole in patients treated with clopidogrel [34].…”

Section: Reduced Bioavailability Of Anti-platelet Drugsmentioning

confidence: 99%

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low-or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

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“…Demographic and mortality data were obtained from the Ontario Health Insurance Plan Registered Persons Database, a registry of all Ontario residents with publically‐funded health insurance, and physicians’ services were identified using OHIP physician claims data. These databases were linked in an anonymous fashion using encrypted Ontario health card numbers, and are routinely used to study drug safety 27, 28, 29, 30, 31, 32.…”

Section: Methodsmentioning

confidence: 99%

A population‐based study of the drug interaction between clopidogrel and angiotensin converting enzyme inhibitors

Cressman

Macdonald

Fernandes

et al. 2015

Brit J Clinical Pharma

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AimsClopidogrel and angiotensin converting enzyme (ACE) inhibitors are commonly co‐prescribed drugs. Clopidogrel inhibits carboxylesterase 1 (CES1), the enzyme responsible for converting prodrug ACE inhibitors (such as ramipril and perindopril) to their active metabolites. The clinical implications of this potential drug interaction are unknown. The clinical consequences of the potential drug interaction between clopidogrel and prodrug ACE inhibitors were examined.MethodsWe conducted a nested case–control study of Ontarians aged 66 years and older treated with clopidogrel between September 1 2003 and March 31 2013 following acute myocardial infarction. Cases were subjects who died or were hospitalized for reinfarction or heart failure in the subsequent year, and each was matched with up to four controls. The primary outcome was a composite of reinfarction, heart failure or death. The primary analysis examined whether use of the prodrug ACE inhibitors ramipril or perindopril was more common among cases than use of lisinopril, an active ACE inhibitor.ResultsAmong 45 918 patients treated with clopidogrel following myocardial infarction, we identified 4203 cases and 14 964 controls. After adjustment, we found no association between the composite outcome and use of perindopril (adjusted odds ratio (aOR) 0.94, 95% confidence interval (CI) 0.76, 1.16) or ramipril (aOR 0.97, 95% CI 0.80, 1.18), relative to lisinopril. Secondary analyses of each element of the composite outcome yielded similar findings.ConclusionsFollowing myocardial infarction, use of clopidogrel with ACE inhibitors activated by CES1 is not associated with an increased risk of adverse cardiovascular outcomes relative to lisinopril. These findings suggest that the recently described drug interaction between clopidogrel and prodrug ACE inhibitors is of little clinical relevance.

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A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

Cited by 655 publications

References 30 publications

Incidence and Economic Burden of Adverse Drug Reactions among Elderly Patients in Ontario Emergency Departments

Incidence and Economic Burden of Adverse Drug Reactions among Elderly Patients in Ontario Emergency Departments

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

A population‐based study of the drug interaction between clopidogrel and angiotensin converting enzyme inhibitors

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