Abstract 807: Anti-inflammatory Therapy By Intensive Cholesterol Lowering Treatment Improves Hemostatic Balance In Elderly Patients With Atrial Fibrillation And Moderate Oral Anticoagulation Therapy
Purpose: In elderly patients with atrial fibrillation (AF) silent ischemic brain infarctions occur despite adequate oral anticoagulation therapy (OAC). Thrombosis is closely related to inflammation, which is often present in AF. The aim of this study was to evaluate the benefit of anti-inflammatory therapy by intensive cholesterol lowering therapy in elderly AF patients with adequate OAC.
Methods: 34 elderly (69 – 85 years old) were randomized double blind to atorvastatin 40 mg + ezetimibe 10 mg (n = 17) or placebo (n = 17) on top of OAC (target INR 2.5–3.5) for one year. Every 3 months inflammatory mediators (Multiplex assay with 27 cytokines, chemokines and growth factors) and hemostatic parameters (the Nijmegen Hemostatic Assay for evaluation of the hemostatic and fibrinolytic activity (Endogenous Thrombin Potential (ETP) and Plasmin Peak Height (PPH) respectively) were measured.
Results: Three patients discontinued in the treatment group (one myalgia, two liver enzyme increase), leaving 14 patients for evaluation. The anti-inflammatory effect in the treatment arm was reflected by a significant decrease in hs-CRP, FGF, G-CSF, GM-CSF, IL-1ra, IL-9, IL-13, IL-17 and interferon-γ(p<0.05). VEGF and IL-8 showed a trend towards decrease (0.05<p<0.10). No inflammatory mediators increased during the trial. Despite adequate OAC, an ETP (563 FU/min) was still present and active but decreased during treatment (521 FU/min)(p = 0.058) compared to the placebo group. The PPH increased more than 50% during intervention (753 FU/min to 1259 FU/min) (p = 0.004) and no significant changes occurred with placebo. No hemorrhagic complications occurred.
Conclusion: This study demonstrates that despite OAC with moderate INR (2.5–3.5) thrombin activity may still be present. Intensive cholesterol lowering with atorvastatin 40 mg + ezetemibe 10 mg was safe and well tolerated; the anti-inflammatory effect was accompanied by reduction of thrombus forming activity and increase of fibrinolytic activity. Higher INR levels increase the risk of hemorrhagic strokes in the elderly; larger clinical trials should determine whether intensive cholesterol lowering therapy is a good alternative to further reduce ischemic damage in elderly AF patients treated with moderate OAC.