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

Autor: Erin M. Macdonald, Alex M. Cressman, Muhammad Mamdani, Tara Gomes, Kimberly A. Fernandes, J. Michael Paterson, David N. Juurlink
Rok vydání: 2015
Předmět:
Male
Ramipril
medicine.medical_specialty
Ticlopidine
Databases
Factual
Myocardial Infarction
Angiotensin-Converting Enzyme Inhibitors
030204 cardiovascular system & hematology
030226 pharmacology & pharmacy
03 medical and health sciences
angiotensin converting enzyme inhibitors
0302 clinical medicine
Lisinopril
Recurrence
Internal medicine
Perindopril
Humans
Medicine
Drug Interactions
Pharmacology (medical)
cardiovascular diseases
Aged
Heart Failure
Pharmacology
clopidogrel
biology
business.industry
Pharmacoepidemiology
Angiotensin-converting enzyme
Clopidogrel
mortality
3. Good health
congestive heart failure
Treatment Outcome
Case-Control Studies
ACE inhibitor
Cardiology
biology.protein
Platelet aggregation inhibitor
Drug Therapy
Combination
Female
business
Platelet Aggregation Inhibitors
circulatory and respiratory physiology
medicine.drug
Zdroj: British Journal of Clinical Pharmacology
ISSN: 1365-2125
0306-5251
Popis: Aims Clopidogrel 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. Methods We 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. Results Among 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. Conclusions Following 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.
Databáze: OpenAIRE
Externí odkaz: