Update on Stroke Care

Educational Objectives

The goal of this program is to improve the management of systolic heart failure (HF) and prevent recurrent strokes and strokes due to atrial fibrillation. After hearing and assimilating this program, the clinician will be better able to:

1. Prescribe appropriate drugs for primary and secondary prevention of stroke.

2. Implement the current guidelines for rhythm monitoring after a cryptogenic stroke or transient ischemic attack.

Summary

Antiplatelet agents: 4 agents approved for secondary prevention; decrease risk for stroke, MI, and death; ticlopidine not used clinically (can cause thrombotic thrombocytopenic purpura)

Aspirin: aspirin-dipyridamole (Aggrenox) provides only 50 mg/day of aspirin (effectiveness of low doses of aspirin not well studied; speaker often adds aspirin 81 mg to dose); risk for gastrointestinal bleeding higher in patients on daily aspirin than in patients not on aspirin (but overall risk small); typically used in patients naive to treatment

Clopidogrel (Plavix): large study found risk for ischemic stroke, MI, and vascular death significantly lower in patients on clopidogrel than in patients on aspirin (analysis of stroke alone found smaller effect that did not reach statistical significance); results of Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study failed to show that aspirin-dipyridamole not inferior; effectiveness decreased by proton pump inhibitors (PPIs; speaker recommends switch to histamine-2 blocker); if PPI necessary, pantoprazole (Protonix) preferred over omeprazole

Aspirin-dipyridamole: as effective as aspirin; headaches occur in ≤40% of patients, but improve over time; advise patients about headaches but instruct them to continue taking drug (or substitute with aspirin); give twice daily

Combination of aspirin and clopidogrel: Management of Atherothrombosis with Clopidogrel in High-Risk Patients (MATCH) trial followed patients for 3.5 yr and found no significant difference in effectiveness between combination and clopidogrel alone (risk for major bleeding increased with addition of aspirin); 2014 American Heart Association (AHA) — American Stroke Association (ASA) guidelines state aspirin and clopidogrel given <24 hr after minor ischemic event may prevent recurrent stroke within 3 mo (therapy probably ineffective if initiated after >24 hr, and should not be given for >90 days); although studies of clopidogrel do not prove its superiority, efficacy probably equal to that of aspirin-dipyridamole, and safety and tolerability likely better

2014 AHA-ASA guidelines: routine platelet function testing should not be used to guide modification of current antiplatelet therapy; no clinical trials have indicated that switching antiplatelet agents reduces risk; antiplatelet therapy more effective than anticoagulation for noncardioembolic ischemic stroke or transient ischemic attack (TIA); aspirin monotherapy, aspirin-dipyridamole, or clopidogrel reasonable options; therapy should be individualized; consider combination for small stroke or TIA if started within 24 hr and continued for 90 days; long-term use of combination increases risk for bleeding (give only in specific circumstances [eg, CAD, stroke])

Failure of treatment with aspirin: no evidence supports benefit of increasing dose; speaker’s recommendations — if patient not on medication, give aspirin 325 mg in hospital and discharge on 81 mg (safer long-term dose); if failure occurs, add clopidogrel without loading (5 days required to achieve therapeutic effect); after few weeks on combination therapy (optimal duration unknown), discontinue aspirin

Atrial fibrillation: epidemiology — more common as individuals age; leading cause of arrhythmia; causes 10% to 12% of strokes; CHADS2 or CHA2DS2-VASc scores can be used to predict risk (most effective for primary prevention); ≈10% of patients with stroke have new AF detected during hospital stay; monitor with ECG for ≥24 hr; Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification — 5 subtypes include large-artery atherosclerosis, cardioembolism, small-vessel occlusion, stroke of other determined etiology, and stroke of undetermined etiology

Cryptogenic Stroke and Underlying AF (CRYSTAL AF) study: compared cardiac monitors with conventional follow-up in patients >40 yr of age with aphasia, limb weakness, or hemianopsia in past 90 days; at 6 mo, AF detected in ≈9% of patients in cardiac monitor group vs 1.4% in control group; 41 days required for detection in cardiac monitor group; at 12 mo, AF found in 12.5% of patients in cardiac monitor group vs 2% in control group; significance of brief events of AF unknown

30-Day Cardiac Event Monitor Belt for Recording AF After a Cerebral Ischemic Event (EMBRACE) trial: AF detection rate in 30-day monitoring group 16%, vs 3.2% with 24-hr Holter monitoring for 1 additional day; ambulatory Holter monitoring found to be superior for detecting AF lasting ≥2.5 min; detection of brief episodes considered important by investigators

CRYSTAL AF and EMBRACE findings: not reflected in 2014 AHA-ASA guidelines; current guidelines state that, for cryptogenic stroke or TIA, prolonged rhythm monitoring (≈30 days) reasonable if performed within 6 mo

Management: warfarin — reduces risk for nonvalvular AF; international normalized ratio (INR) goal 2 to 3; dabigatran, rivaroxaban, and apixaban — approved by Food and Drug Administration (with exception of some dosing issues); choice of appropriate drug — consider individual factors, cost, and risk for intracranial hemorrhage; use of warfarin, dabigatran, and rivaroxaban reasonable for primary prevention (use of these agents as well as apixaban reasonable for secondary prevention); tissue plasminogen activator (tPA) not warranted if patient on dabigatran, rivaroxaban, or apixaban

Combination of anticoagulation and antiplatelet therapy: not shown to decrease risk for stroke or MI, but increased risk for bleeding clearly demonstrated; only exception clinically apparent CAD, especially acute coronary syndrome or drug-eluting stent

Timing: in patients who present with AF, risk for early stroke ≤8% in 2 wk; American College of Chest Physicians recommends initiating warfarin within 2 wk of cardioembolic stroke, except if stroke large or risk factors for hemorrhage present; tPA not warranted if warfarin therapeutic

Speaker’s recommendations: in acute setting, hold warfarin if patient has stroke; do not reverse warfarin unless patient bleeding (hemorrhagic stroke); start aspirin unless large area of hemorrhagic conversion present (based on computed tomography [CT]); if stroke small with no hemorrhagic conversion, resume anticoagulation within 1 wk (bridging not advised); discontinue aspirin when therapeutic effect achieved; if stroke large with hemorrhagic conversion visualized on CT, obtain CT before resuming anticoagulation; if CT stable, resume anticoagulation in 10 to 14 days, with no bridging, and discontinue aspirin when therapeutic effect achieved; if warfarin treatment fails, look for other causes and consider different agent

Acknowledgments

Dr. Hobbs was recorded at Contemporary Outpatient Cardiovascular Medicine, held October 24, 2014, in Beachwood, OH, and sponsored by the Cleveland Clinic Medicine Institute. For information about upcoming CME activities from Cleveland Clinic Medicine Institute, please visit www.ccfcme.org. Dr. Lundeen was recorded at the Washington Chapter Scientific Meeting, held November 6-8, 2014, in Seattle, WA, and sponsored by the American College of Physicians. For information about upcoming CME activities from the American College of Physicians, please visit www.acponline.org. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Suggested Readings

Al-Shahi Salman R, Dennis MS: Antiplatelet therapy may be continued after intracerebral hemorrhage. Stroke, 2014 Oct;45(10):3149-50; Ambrosy AP et al: B-type natriuretic peptide assessment in ambulatory heart failure patients: insights from IMPROVE HF. J Cardiovasc Med (Hagerstown), 2012 Jun;13(6):360-7; Arnarsdottir L et al: Comparative evaluation of treatment with low-dose aspirin plus dipyridamole versus aspirin only in patients with acute ischaemic stroke. BMC Neurol, 2012 Aug 6;12:67; Berkowitz AL et al: Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings. Neurology, 2014 Sep 9;83(11):1004-11; Braunwald E: Heart failure. JACC Heart Fail, 2013 Feb;1(1):1-20; Collerton J et al: Utility of NT-proBNP as a rule-out test for left ventricular dysfunction in very old people with limiting dyspnoea: the Newcastle 85+ Study. BMC Cardiovasc Disord, 2014 Sep 26;14:128; Facchini E et al: Systolic heart failure and cardiac resynchronization therapy: a focus on diastole. Int J Cardiovasc Imaging, 2014 Jun;30(5):897-905; Hankey GJ: Intracranial hemorrhage and novel anticoagulants for atrial fibrillation: what have we learned? Curr Cardiol Rep, 2014 May;16(5):480; Kachboura S et al: Cardiac resynchronization therapy allows the optimization of medical treatment in heart failure patients. Ann Cardiol Angeiol (Paris), 2014 Feb;63(1):17-22; Kanda S et al: Effects of a combination of losartan and hydrochlorothiazide in patients with hypertension and a history of heart failure. Tokai J Exp Clin Med, 2014 Mar 20;39(1):1-4; Krum H, Driscoll A: Management of heart failure. Med J Aust, 2013 Sep 2;199(5):334-9; Lang K et al: Anticoagulant use for the prevention of stroke in patients with atrial fibrillation: findings from a multi-payer analysis. BMC Health Serv Res, 2014 Jul 28;14:329; McGrath ER et al: Investigators of the Ontario Stroke Registry. Antithrombotic therapy after acute ischemic stroke in patients with atrial fibrillation. Stroke, 2014 Dec;45(12):3637-42; Nevzorov R et al: Effect of beta blocker therapy on survival of patients with heart failure and preserved systolic function following hospitalization with acute decompensated heart failure. Eur J Intern Med, 2012 Jun;23(4):374-8; Rognoni C et al: Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. Clin Drug Investig, 2014 Jan;34(1):9-17; Sardar P et al: New oral anticoagulants are not superior to warfarin in secondary prevention of stroke or transient ischemic attacks, but lower the risk of intracranial bleeding: insights from a meta-analysis and indirect treatment comparisons. PLoS One, 2013 Oct 25;8(10):e77694; Valente MA et al: Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J, 2014 May 14;35(19):1284-93.

Readings

Suggested Readings

Al-Shahi Salman R, Dennis MS: Antiplatelet therapy may be continued after intracerebral hemorrhage. Stroke, 2014 Oct;45(10):3149-50; Ambrosy AP et al: B-type natriuretic peptide assessment in ambulatory heart failure patients: insights from IMPROVE HF. J Cardiovasc Med (Hagerstown), 2012 Jun;13(6):360-7; Arnarsdottir L et al: Comparative evaluation of treatment with low-dose aspirin plus dipyridamole versus aspirin only in patients with acute ischaemic stroke. BMC Neurol, 2012 Aug 6;12:67; Berkowitz AL et al: Aspirin for secondary prevention after stroke of unknown etiology in resource-limited settings. Neurology, 2014 Sep 9;83(11):1004-11; Braunwald E: Heart failure. JACC Heart Fail, 2013 Feb;1(1):1-20; Collerton J et al: Utility of NT-proBNP as a rule-out test for left ventricular dysfunction in very old people with limiting dyspnoea: the Newcastle 85+ Study. BMC Cardiovasc Disord, 2014 Sep 26;14:128; Facchini E et al: Systolic heart failure and cardiac resynchronization therapy: a focus on diastole. Int J Cardiovasc Imaging, 2014 Jun;30(5):897-905; Hankey GJ: Intracranial hemorrhage and novel anticoagulants for atrial fibrillation: what have we learned? Curr Cardiol Rep, 2014 May;16(5):480; Kachboura S et al: Cardiac resynchronization therapy allows the optimization of medical treatment in heart failure patients. Ann Cardiol Angeiol (Paris), 2014 Feb;63(1):17-22; Kanda S et al: Effects of a combination of losartan and hydrochlorothiazide in patients with hypertension and a history of heart failure. Tokai J Exp Clin Med, 2014 Mar 20;39(1):1-4; Krum H, Driscoll A: Management of heart failure. Med J Aust, 2013 Sep 2;199(5):334-9; Lang K et al: Anticoagulant use for the prevention of stroke in patients with atrial fibrillation: findings from a multi-payer analysis. BMC Health Serv Res, 2014 Jul 28;14:329; McGrath ER et al: Investigators of the Ontario Stroke Registry. Antithrombotic therapy after acute ischemic stroke in patients with atrial fibrillation. Stroke, 2014 Dec;45(12):3637-42; Nevzorov R et al: Effect of beta blocker therapy on survival of patients with heart failure and preserved systolic function following hospitalization with acute decompensated heart failure. Eur J Intern Med, 2012 Jun;23(4):374-8; Rognoni C et al: Apixaban, dabigatran, and rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. Clin Drug Investig, 2014 Jan;34(1):9-17; Sardar P et al: New oral anticoagulants are not superior to warfarin in secondary prevention of stroke or transient ischemic attacks, but lower the risk of intracranial bleeding: insights from a meta-analysis and indirect treatment comparisons. PLoS One, 2013 Oct 25;8(10):e77694; Valente MA et al: Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J, 2014 May 14;35(19):1284-93.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose. In her lecture, Dr. Lundeen presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

 Dr. Lundeen was recorded at the Washington Chapter Scientific Meeting, held November 6-8, 2014, in Seattle, WA, and sponsored by the American College of Physicians. For information about upcoming CME activities from the American College of Physicians, please visit www.acponline.org. The Audio Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM621302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.