Safety of the Combination of Intensive Cholesterol-Lowering Therapy with Oral Anticoagulation Medication in Elderly Patients with Atrial Fibrillation: A Randomized, Double-Blind, Placebo-Controlled Study
Abstract
Background The incidence of atrial fibrillation (AF) is very high in the elderly, and often oral anticoagulation (OAC) is indicated to prevent thromboembolism.Objective The aim of this study was to evaluate the safety of combining intensive cholesterol-lowering therapy with OAC in elderly patients with AF.Methods In a randomized, double-blind trial, 34 patients received OAC plus atorvastatin 40 mg/day and ezetimibe 10 mg/day versus placebo over 1 year. Dose adjustments of OAC served as an indicator of an interaction between HMG-CoA reductase inhibitors (statins) and OAC. Safety was evaluated by the occurrence of bleeding and a rise in AST, ALT and creatine phosphokinase.Results Compared with a 6-month pre-intervention period, the mean daily dose +/- standard error of OAC was 4.4 +/- 1.5% lower in the treatment group (p = 0.003) and virtually the same in the placebo group (change from baseline: -0.1 +/- 1.3%, p = 0.96). The mean daily dose of OAC stabilized after 3 months. In the 6-month post-intervention period, OAC dosing showed no statistically significant change from baseline: -1.9 +/- 1.9% in the placebo arm and -2.6 +/- 2.1% in the intervention arm.Conclusion We conclude that in elderly AF patients treated with OAC, intensive cholesterol-lowering therapy (atorvastatin 40 mg/day and ezetimibe 10 mg/day) is well tolerated. No increased risk in bleeding was found.
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The AUC of blood statin levels increases when statins are used in combination with drugs that are CYP substrates.
“It has been reported that the AUC of the blood statin levels increases when they are used in combination with drugs that are CYP substrates713).”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [713]
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- Authors
- Enajat, M., Teerenstra, S., van Kuilenburg, J. T., van Sorge-Greve, A. H. N., Albers-Akkers, M. T. H., Verheugt, F. W. A., & Pop, G. A. M.
- Affiliations
- Radboud University Medical Center (NL)
- Corresponding author
- Enajat, Morteza
- Venue
- Drugs & Aging
- Published
- 2009-07
- Volume
- 26
- Issue
- 7
- Pages
- 585-593
- ISSN
- 1170-229X (ISSN-L)
- OpenAlex
- W2058711306
- Cited by
- 13
- References
- 19
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 1 · 2018: 3 · 2017: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drugs & Aging (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- atrial fibrillation, oral anticoagulation, cholesterol-lowering therapy, atorvastatin, ezetimibe, statin-drug interactions, elderly patients, bleeding risk, drug safety, dose adjustment, thromboprophylaxis
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Anticholesteremic Agents, Anticoagulants, Atrial Fibrillation, Dose-Response Relationship, Drug, Double-Blind Method, Drug Interactions, Drug Therapy, Combination, Female, Hemorrhage, Humans, Male, Placebo Effect, Endpoint Determination, Medication Adherence
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