Andrew Liu, BSc Hon, BScPhm, RPh, Clinical Pharmacist, Thrombosis Service, Toronto East General Hospital, Toronto, ON.
Carmine Stumpo, BScPhm, PharmD, RPh, Director, Pharmacy and Emergency Services, Toronto East General Hospital, Toronto, ON.

Warfarin-drug interactions are often encountered in the care of older adults. Interactions may be classified as pharmacokinetic, resulting in changes in serum warfarin concentrations, or pharmacodynamic, resulting in changes in hemostasis or platelet function. Knowledge of these mechanisms of warfarin-drug interactions may help identify warfarin interactions, facilitate prescribing decisions, and assist with appropriate monitoring.
Key words: warfarin, drug interactions, anticoagulants, cytochrome P-450 enzyme system, older adults.

Sarah E. Wilson, MSc, MD, PGY1, Internal Medicine, University of Toronto, Toronto, ON.
Mark A. Crowther, MD, MSc, Associate Professor of Medicine, Department of Medicine, McMaster University, Hamilton, ON.

Warfarin reduces the risk of thrombotic complications in a wide range of patients and appears to be particularly effective in older adults. Warfarin initiation should be undertaken with care in the older adults because they are likely to require smaller maintenance doses to achieve the same target international normalized ratio (INR). Inappropriate prescribing of medications among older adults increases the risk of drug interactions that may alter warfarin anticoagulation. Such interactions should be anticipated and monitored to ensure that over- or under-anticoagulation do not persist. A range of strategies are available to follow warfarin therapy in the outpatient setting to ensure safe and effective anticoagulation.
Key words: warfarin, anticoagulation, vitamin K, atrial fibrillation.

Rajneesh Calton, MD, FACC, Division of Cardiac Electrophysiology, University Health Network, Toronto General Hospital, Toronto, ON.
Vijay Chauhan, MD, FRCPC, Division of Cardiac Electrophysiology, University Health Network, Toronto General Hospital, Toronto, ON.
Kumaraswamy Nanthakumar, MD, FRCPC, Division of Cardiac Electrophysiology, University Health Network, Toronto General Hospital, Toronto, ON.

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia worldwide, with an estimated prevalence of 0.4% in the general population. Despite recent advances in our understanding of the mechanism and consequences of AF, effective therapy for patients with AF remains difficult in many patients. Antiarrhythmic drug therapy includes control of ventricular rate as well as restoration and maintenance of sinus rhythm. The risks and benefits of each treatment modality must be assessed according to each individual patient’s circumstances. Anticoagulation for stroke prevention is a critical component of AF management that is currently underprescribed. Anticoagulation with vitamin K antagonists, such as warfarin, remains the treatment of choice for preventing stroke and cardio embolism. The oral direct thrombin inhibitor ximelagatran has the potential to favourably influence the management of patients with AF by maximizing the potential of anticoagulation for stroke prevention.
Key words: atrial fibrillation, anticoagulation, rate control, warfarin, ximelagatran, antiarrhythmic.

Findings of a Provocative New Meta-Analysis

Jason M. Burstein, MD
Internal Medicine Resident,
University of Toronto,
Toronto, ON.

Shabbir M.H. Alibhai, MD, MSc, FRCP(C)
Clinical Assistant, Internal
Medicine & Geriatrics,
University Health Network, Toronto, ON.

Introduction
Atrial fibrillation is a common cardiac condition that challenges many physicians, including primary care and emergency doctors, general internists, geriatricians and cardiologists. One of the best-understood and most studied complications is cardio-embolic stroke. While management of atrial fibrillation may seem straightforward, it is interesting to note that there are still large variations in practice patterns, and a recent meta-analysis was contradictory to many previous studies and guidelines. This paper will focus on the epidemiology and treatment of atrial fibrillation in the older population and will examine both the reasons for variations in practice pattern and the conflicting evidence in major medical journals.

Epidemiology and Causes of Atrial Fibrillation
Age is perhaps the most important influence on the incidence and prevalence of disease. The prevalence rate of atrial fibrillation is 2-3% at age 60 to 65 and 8-10% at age 80. Up to 70% of all affected patients are at least 65 years old. The incidence of atrial fibrillation before age 50 is 0.

Lawrence Papoff

Warfarin is an important tool in the prevention of thromboembolisms. Prescribing the drug to the elderly, and monitoring their progress while on the drug, however, are becoming increasingly complex matters, requiring careful attention to patient's blood levels, as measured by International Normalized Ratios (INRs) and in-depth knowledge of the patient.

Lilia Malkin, BSc

According to a study conducted by Dr. Elaine Hyle and associates at the Massachusetts General Hospital and Harvard Medical School in Boston and reported in the March 4, 1998 issue of the Journal of the American Medical Association (JAMA), acetaminophen significantly increases the level of anticoagulation, measured and commonly reported as the international normalized ratio (INR). Other important risk factors for increased anticoagulation identified in the study included decreased food intake, diarrhea, and increased warfarin dosage, as well as a recently initiated course of antibiotics or other medications previously known to augment the response to warfarin. Hylek and associates also identified factors that inversely affected the INR, such as alcohol and increased dietary intake of Vitamin K.