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

Drugs Aging. 2009;26(7):585-93. doi: 10.2165/10558450-000000000-00000.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / adverse effects*
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Interactions
  • Drug Therapy, Combination
  • Endpoint Determination
  • Female
  • Hemorrhage / etiology
  • Humans
  • Male
  • Medication Adherence
  • Placebo Effect

Substances

  • Anti-Inflammatory Agents
  • Anticholesteremic Agents
  • Anticoagulants