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Update on Family Medicine: Oral Anticoagulants, Stroke Management, Ovarian Cancer

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 63rd McGill Annual Refresher Course for Family Physicians

Montréal, Quebec / November 26-28, 2012

Montreal - At this year’s McGill Refresher Course, delegates heard about potentially practice-altering patient management strategies for common conditions. In a plenary session, they were informed about using dabigatran, rivaroxaban and apixaban vs. warfarin for stroke prevention. A related workshop looked at selecting the right therapies for the right patients. In another plenary session, delegates learned about a novel, post-stroke checklist. In a third session, an expert dispelled myths about screening for ovarian cancer.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

In a plenary session entitled “New Anticoagulation Drugs,” Dr. Vicky Tagalakis, Associate Professor of Medicine, McGill University, shed light on using these agents to prevent stroke in patients with non-valvular atrial fibrillation (AF). Dabigatran and rivaroxaban are approved and apixaban is expected to be approved soon for this indication. Rivaroxaban is given once daily, whereas dabigatran and apixaban are dosed twice daily.

Preventing Stroke in AF

Dr. Tagalakis reported that 3 multicentre trials of these agents vs. warfarin, each with over 14,000 patients, have been published: RE-LY with dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy) (N Engl J Med 2009;361:1139-51), ROCKET-AF with rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) (N Engl J Med 2011; 365:883-91) and ARISTOTLE with apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) (N Engl J Med 2011; 365:981-92). All agents proved superior (dabigatran 150 mg b.i.d., apixaban 5 mg b.i.d.) or non-inferior (dabigatran 110 mg b.i.d., rivaroxaban 20 mg once-daily) to warfarin for preventing stroke, and less intracranial bleeding events were reported. There was less overall bleeding with apixaban than with warfarin, but GI bleeding was greater with dabigatran than with warfarin.

In Canada, dabigatran 150 mg b.i.d. and 110 mg b.i.d. are approved to prevent stroke and systemic embolism in patients with nonvalvular AF—with the lower dose recommended for patients over age 75 or those with a higher bleeding risk. In 2010, the Régie de l’assurance maladie du Québec (RAMQ) approved dabigatran as a médicament d’exception for stroke prevention for certain patients with non-valvular AF. Dabigatran is not recommended for patients with a creatinine clearance below 30 mL/min. Patients receiving the drug need frequent renal-function monitoring because 80% is excreted via the kidneys (similar to the 67% renal excretion seen with rivaroxaban). Physicians may prescribe the 110 mg dose for patients older than 75 years of age and a creatinine clearance of 30 to 50 mL/min, if they closely monitor patient renal function. In RE-LY, patients in the warfarin arm had time in therapeutic range (TTR) of 64%. Another study showed that patients who can maintain a higher TTR (>72.6%) on warfarin may see little or no benefit from novel oral anticoagulants (Lancet 2010;376:975-83.)

Rivaroxaban was approved for stroke prevention in the US in October 2011 and by Health Canada the following month. Because it is dosed once daily and has a short half life (8 to 9 hours vs. 12 to 17 hours for dabigatran), possible stroke risk is a concern when a patient is transitioned off rivaroxaban to another anticoagulant or when a dose is missed. In May 2012, similarly to dabigatran, the RAMQ approved rivaroxaban as a médicament d’exception at a dose of 20 mg daily for patients with a creatinine clearance above 50 mL/min and 15 mg daily for patients with a creatinine clearance of 30 to 50 mL/min.

Unlike warfarin, the new oral anticoagulants are simple to dose, do not interact with food and do not require monitoring of anticoagulant levels. However, physicians need to educate patients to ensure compliance. These new agents have a shorter half life than warfarin and their anticoagulant effect declines quickly if doses are missed. Physicians need to be cautious when prescribing drugs to older patients who may develop renal impairment. Unlike warfarin, which can be reversed by prothrombin complex concentrate (Octaplex), there is no antidote for the new agents.

In a workshop, Dr. Tagalakis stated that “the ideal anticoagulant has not been discovered yet.” The Canadian Cardiovascular Society Guidelines update for stroke prevention in AF suggest that “most patients should receive dabigatran, rivaroxaban or apixaban in preference to warfarin” (Can J Cardiol 2012;28:125-36). For some patients, stroke prevention with warfarin is more appropriate. These include patients with good INR control, renal failure, mechanical heart valves, dyspepsia, history of GI bleeding or poor compliance.

Candidates for the new oral anticoagulants include patients with unexplained poor warfarin control, limited access to a coagulation laboratory, unavoidable drug-drug interactions, a history of intracranial bleeding or new patients who are about to receive anticoagulation for non-valvular AF. For patients “in the gray zone”—over age 75 years with a creatinine clearance of 30 to 49 mL/min—warfarin is probably the safest option. Black box warning state that discontinuing rivaroxaban increases thrombotic events and from a meta-analysis, dabigatran increases the risk of a myocardial infarction compared with controls. Regular follow-up of patients receiving these new agents is essential to assess compliance and any adverse events. “Renal function should be monitored every 3 months,” Dr. Tagalakis reported. If a planned procedure has a low bleeding risk (e.g., cataract surgery), there is no need to stop the new agent. If the bleeding risk is greater, the agent should be stopped 1 to 6 days earlier, depending on patient renal function.

Post-Stroke Checklist

In another plenary session, Dr. Theodore Wein, Assistant Professor of Neurology and Neurosurgery, McGill University, spoke about “Acute and Chronic Stroke Management and 11 Questions You Should Always Ask Your Stroke Patients.” “To me, every transient ischemic attack (TIA) patient should be evaluated urgently,” he reported. According to the “Canadian Best Practice Recommendations for Stroke Care,” which are available at the http://www.strokebestpractices.ca website, patients presenting to a family physician’s office within a week of a suspected TIA should be immediately evaluated for stroke management. An antiplatelet agent—ASA, ASA plus dipyridamole or clopidogrel—should be given for secondary prevention. A statin should be prescribed to most patients with a high risk of a cardiovascular event. Patients should receive antihypertensives to reach a consistent target blood pressure below 140/90 mm Hg. Symptomatic patients with >50% carotid stenosis may receive carotid endarterectomy, which should be done within 14 days. Patients with TIA and AF should begin treatment with a new oral anticoagulant or warfarin right after brain imaging has excluded intracerebral hemorrhage or a large infarction.

In a survey of stroke survivors in the UK, 33% did not feel prepared to manage their problems upon discharge (Br J Gen Pract 2003;53:137-42). To help physicians better manage stroke survivors, an international group of experts, the Global Stroke Community Advisory Panel, of which Dr. Wein is a member, developed a post-stroke checklist. The checklist has 11 questions—about secondary stroke prevention, activities of daily living, mobility, spasticity, pain, incontinence, communication, mood, cognition, life after stroke and relationship with family—that clinicians ask patients. An article about this checklist has been accepted for publication.

Need to Rethink Ovarian Cancer

Dr. Lucy Gilbert, Professor of Oncology and Obstetrics and Gynecology, McGill University presented a plenary session entitled “Ovarian Cancer: Is Early Diagnosis Possible?” Although ovarian cancer is the leading cause of death from a gynecologic cancer, cure rates have only increased about 2% over the past 30 years, she reported. The death rate is high because 70% of these cancers are detected at stage 3 to 4. Three trials that screened about 340,000 women in Japan (Int J Gynecol Cancer 2008;18:414-20), the UK (Lancet Oncol 2009;10:327-40) and the US (JAMA 2011;305:2295-303) found that measuring levels of cancer antigen 125 (CA125) or performing transvaginal ultrasound tests did not lead to earlier cancer diagnosis or fewer deaths, and resulted in high rates of false negatives and false positives. However, her research team’s DOvE (Diagnosing Ovarian Cancer Early) study, found that screening women who had the vague symptoms of ovarian cancer—including bloating, abdominal distention, feeling full after eating a little, urinary frequency and abdominal or pelvic discomfort—detected 10 times the number of cancers as in the general population. The study’s recently published pilot phase also reported that many of the ovarian cancer originated outside the ovaries (Lancet Oncol 2012;13:285-91). “Everything we thought we knew about ovarian cancer probably is wrong—the name, origin, staging and the screening tests,” said Dr. Gilbert. The take home message is “Do not offer screening, but take note of vague symptoms.”

Summary

This year’s meeting offered 23 plenary sessions and 70 workshops with high-caliber speakers who presented information that can transform practice, said Dr. Ivan Rohan, Associate Dean, Continuing Health Professional Education and Assistant Professor, Department of Family Medicine, McGill University. Among the meeting highlights were these 3 sessions that presented a timely review of the new oral anticoagulant agents, news about a checklist to help manage stroke patients and a talk by an expert who has changed the way we view ovarian cancer.  

 

Mednet reports which have been accredited by McGill University under the MedPoint Accredited Conference Report Series are eligible for Mainpro-M1 and MOC Program credits.

© 2012 Mednet Inc. All rights reserved. Priority Press™ is an independent medical news reporting service providing educational updates reflecting peer opinion from accredited scientific medical meetings worldwide and/or published peer-reviewed medical literature. Distribution of this educational publication is made possible through the support of industry under written agreement that ensures independence. Views expressed are those of the participants and do not necessarily reflect those of the publisher, McGill University or the sponsor. No claims or endorsements are made for any products, uses or doses. Specific medicines or treatment strategies discussed in this publication may not yet be approved in Canada. Prior to prescribing any medication, the complete prescribing information in Canada, including indications, contraindications, warnings, precautions, and adverse effects should be consulted. No part of this publication may be reproduced in any form or distributed without written consent of the publisher. Information provided herein is not intended to serve as the sole basis for individual care. Our objective is to facilitate physicians’ and allied health care providers’ understanding of current trends in medicine. Your comments are encouraged.

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