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5. Non-AF trial evidence and special circumstances in which aspirin is recommended

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Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Stroke in Patients with a History of Atrial Fibrillation: Subgroup Analysis of the CHARISMA Randomized Trial.

Cerebrovasc Dis 2008;25:344-347

Hart RG, Bhatt DL, Hacke W, Fox KA, Hankey GJ, Berger PB, Hu T, Topol EJ; CHARISMA Investigators.  Department of Neurology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. hartr@uthscsa.edu

Background: Aspirin offers modest reduction in stroke in patients with atrial fibrillation. Whether combination of aspirin with clopidogrel offers additional protection is unclear.

Methods: Post-hoc subgroup analysis of 593 participants with a history of atrial fibrillation in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) randomized trial testing clopidogrel 75 mg per day plus aspirin (75-162 mg per day) vs. aspirin alone in patients with stable cardiovascular disease or multiple cardiovascular risk factors.

Results: Mean patient age was 70 years, 78% were men, and hypertension, heart failure and diabetes were present in 78, 20 and 44%, respectively. During a median follow-up of 2.3 years, stroke (ischemic and hemorrhagic) occurred in 15 of 298 assigned to clopidogrel plus aspirin and in 14 of 285 given aspirin alone (hazard ratio, HR, 1.03, 95% CI 0.49-2.1). There was no difference in all-cause mortality (HR 1.1, 95% CI 0.6-1.9) or in the composite of stroke, myocardial infarction, or vascular death (HR = 1.2, 95% CI 0.7-2.0). Severe/fatal extracranial hemorrhage occurred in 6 patients with combination vs. 3 with aspirin alone.

Conclusions: This post-hoc subgroup analysis does not support the use of this combination over aspirin alone in patients with a history of atrial fibrillation pending results of ongoing larger randomized trials.

Hart RG, Bhattb DL, Hacke W, et al. for the CHARISMA Investigators. Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Stroke in Patients with a History of Atrial Fibrillation: Subgroup Analysis of the CHARISMA Randomized Trial. Cerebrovasc Dis 2008;25:344-347 (DOI: 10.1159/000118380). http://www.ncbi.nlm.nih.gov/pubmed/18303254

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting.

Thromb Haemost. 2010 Jan;103(1):13-28.

Lip GY, Huber K, Andreotti F, Arnesen H, Airaksinen KJ, Cuisset T, Kirchhof P, Marín F; European Society of Cardiology Working Group on Thrombosis. B18 7QH, United Kingdom. g.y.h.lip@bham.ac.uk

There remains uncertainty over optimal antithrombotic management strategy for patients with atrial fibrillation (AF) presenting with an acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Clinicians need to balance the risk of stroke and thromboembolism against the risk of recurrent cardiac ischaemia and/or stent thrombosis, and the risk of bleeding. This consensus document comprehensively reviews the published evidence and presents a consensus statement on a 'best practice' antithrombotic therapy guideline for the management of antithrombotic therapy in such AF patients.

Lip GY, Huber K, Andreotti F, et al. European Society of Cardiology Working Group on Thrombosis. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Thromb Haemost. 2010 Jan;103(1):13-28. http://www.ncbi.nlm.nih.gov/pubmed/20062939

Non-AF trial evidence and special circumstances in which aspirin is recommended

I would point out that the role of aspirin, or antiplatelet therapy, is not just seen in AF trials.  I show here a subgroup analysis from the CHARISMA trial. CHARISMA was a trial where aspirin/clopidogrel was compared to aspirin for the prevention of stroke in patients with cardiovascular risk factors.  This is a subgroup analysis, I would stress.  So it’s not necessarily powered for a lot of the endpoints.  What you can see here, numerically, is aspirin/clopidogrel didn’t offer much advantage in terms of stroke and other cardiovascular events.  What you do see is this higher numerical instance of bleeding in the patients on combination aspirin/clopidogrel. 

It is worth highlighting the fact that severe or fatal extracranial bleeds particularly, is much greater by giving aspirin/clopidogrel in combination compared to aspirin alone.  The issue of antiplatelet therapy or aspirin, particularly, in the context of atrial fibrillation is therefore, in terms of chronic stroke prevention, aspirin is not very effective and it’s not any safer.

However, we have other situations where aspirin may still be required.  I show here just a screen shot of a difficult sort of patient, which is the atrial fibrillation patient who presents with an acute coronary syndrome, and who will require acute angioplasty, or stent. Patients with AF who are at moderate to high risk of stroke who have had a recent coronary event and/or a stent.  We are essentially trying to juggle four balls in the air: we’re trying to prevent stroke, we’re trying to prevent recurrent cardiac ischaemia – if they’ve had an acute coronary syndrome, we’re trying to prevent stent thrombosis if they’ve had a recent stent, and fourthly, balancing against the risk of potential major bleeding, particularly an intracranial bleeding by combining antiplatelet therapy with anticoagulant therapy.  So we’re trying to juggle four balls in the air.  The gist of the detailed recommendation in this European consensus document, which is the driver behind the European guidelines on atrial fibrillation management, is the requirement of triple therapy for the initial period, followed by anticoagulant plus single antiplatelet therapy. Then, after a year, if they have stable vascular disease, they can be managed with anticoagulant alone.  So, what determines the duration of triple therapy?  Well, lots of things.  Firstly, bare-metal stent versus drug-eluting stent.  Interventional cardiologists should be encouraged to use a bare-metal stent because there is shorter requirement for combination therapy. Secondly, it depends on the bleeding risk using the HASBLED score, which is a well validated score now for assessing the bleeding risk.  Furthermore, the duration of triple therapy does also depend upon the acuteness of the situation.  Whether it was acute versus elective angioplasty does have a bearing on the duration of antiplatelet therapy.

When aspirin?: Questions

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Please find below additional resources that you might find useful when learning about stroke prevention in AF

GRASP the initiative

A report from October 2012 on the practicalities of GRASP-AF and its benefits for primary care practitioners.  The report incudes a national summary of GRASP-AF patient treatment and a series of recommendations for commissioners and practitioners on the how stroke risk among AF patients can be reduced.
Report download

The AF Report

An expert report on AF and the prevention of stroke in the UK.  The AF Report was written for a general audience and presents a thorough and current distillation of the evidence and issues in AF stroke prevention.  The report also identifies current challenges and areas where action is needed to improve the care of AF patients. Download report

The AF Stroke Risk Calculator

A simple online tool for the calculation of CHADS2 and CHADSVASc scores for AF patients.  The calculator was designed to be intuitive and sufficiently easy-to-use for patients to calculate their own risk of stroke.

NHS IQ: GRASP-AF

The NHS Improving Quality website contains a wealth of helpful, practical information on GRASP-AF

The videos

Below are video clips from Dr Matt Fat and Dr Andreas Wolff on several aspects of AF patient care and the reduction of stroke risk.

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