My patient with atrial fibrillation (AF) with a CHA2DS2-VASc score ≥2 is not a candidate for anticoagulation due to excessive bleeding risk. Does high-dose aspirin provide an effective alternative for stroke prevention in this setting?

 The SPAF (Stroke Prevention in Atrial Fibrillation) trial1 found a 42% reduction in overall risk of stroke with daily aspirin (325 mg). However, critics note that no benefit was observed among patients > 75 y or those with severe stroke.

7 other studies on the topic failed to confirm reduction in the risk of stroke at a range of aspirin doses (25mg bid-1,300mg qd) 2. These studies reported that aspirin is associated with a 19% reduction in stroke incidence (similar to patients with vascular disease), with a 95% CI that crosses zero (-1% to 35%), raising doubts about its actual benefit in AF3. For secondary prevention, aspirin was associated with a 2.5% reduction in the annual risk of stroke. However, these results were influenced by the only trial with a favorable outcome, SPAF-14.

In short, even at higher doses, aspirin may not be the answer for stroke prevention in patients with AF.

 References

  1. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991;84, 527–39.
  2. January CT, Wann LS, Alpert  JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation  2014;130, e199–e267.
  3. European Heart Rhythm Association et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace  2010; 12, 1360–420.
  4. Sabir IN, Matthews GDK,  Huang, CL-H. Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice. Postgrad Med J 2013; 89, 346–51.

 

Contributed by Jacqueline Boehme, M.D., Medical Resident, Mass General Hospital

My patient with atrial fibrillation (AF) with a CHA2DS2-VASc score ≥2 is not a candidate for anticoagulation due to excessive bleeding risk. Does high-dose aspirin provide an effective alternative for stroke prevention in this setting?

Does electroconvulsive therapy (ECT) pose a risk of embolic stroke in patients with atrial fibrillation (AF)?

Acute embolic stroke in the setting of AF without anticoagulation after ECT has been reported in a single case report in the absence of conversion to normal sinus rhythm (1). Several cases of episodic or persistent conversion to normal sinus rhythm (NSR) in patients with AF undergoing ECT have also been reported (in the absence of embolic stroke), leading some to recommend anticoagulation therapy in such patients (2), though no firm data exist.

The mechanism by which ECT promotes cardioversion from AF to NSR is unclear as direct electrical influence of ECT on the heart is thought to be negligible (1). Arrhythmias such as atrial flutter and AF have also been reported after ECT (1). Curiously, ECT is associated with increased 5- hydroxytryptamine (5- HT2)-receptor densities of platelets in patients with depression which may enhance platelet reactivity and increase the risk of embolic stroke (3) even in the absence of cardioversion.

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References

  1. Suzuki H, Takano T, Tominaga M, et al. Acute embolic stroke in a patient with atrial fibrillation after electroconvulsive therapy. J Cardiol Cases 2010; e12-e14. https://www.sciencedirect.com/science/article/pii/S1878540910000113
  2. Petrides G, Fink M. Atrial fibrillation, anticoagulation, electroconvulsive therapy. Convulsive Therapy 1996;12:91-98. https://journals.lww.com/ectjournal/Abstract/1996/06000/Atrial_Fibrillation,_Anticoagulation,_and.4.aspx
  3. Stain-Malmgren R, Tham A, Ǻberg-Wistedt A. Increased platelet 5-HT2 receptor binding after electroconvulsive therapy in depression. J ECT 1998;14:15-24. https://europepmc.org/abstract/med/9661089
Does electroconvulsive therapy (ECT) pose a risk of embolic stroke in patients with atrial fibrillation (AF)?

How should I choose between the direct oral anticoagulants (DOACs)?

Although warfarin has long been the standard treatment for venous thromboembolism (VTE) and thomboprophylaxis in atrial fibrillation (AF), the need for its frequent monitoring, potential drug interactions, and narrow therapeutic window made it far from ideal.

Since 2009, DOACs have become viable alternative agents owing to their more predictable and safer pharmacological profiles. DOACs include several direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) and a direct thrombin inhibitor (dabigatran). Approved indications include: (1) thromboprophylaxis in nonvalvular AF; (2) treatment of deep venous thrombosis or pulmonary embolism; and (3) primary prevention of postoperative VTE. 

Compared to warfarin, DOACs are associated with a reduced risk of intracranial hemorrhage, and in the case of apixaban, lower risk of gastrointestinal bleeding; rivaroxaban and edoxaban have been associated with a higher risk of gastrointestinal bleeding.  

Apixaban is also the only NOAC whose dose can be safely reduced in chronic kidney disease, including those on hemodialysis. 

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References

 

1. Baber U, Mastoris I, and Mehran R. Balancing ischaemia and bleeding risks with novel oral anticoagulants. Nat Rev Cardiol 2014;11:693-703.  https://www.ncbi.nlm.nih.gov/pubmed/25367652 

2. Ansell JE. Universal, class-specific, and drug-specific reversal agents for the new oral anticoagulants. J Thromb Thrombolysis 2016;41:248-52. https://www.ncbi.nlm.nih.gov/pubmed/26449414

 

Contributed by William L. Hwang, MD, Mass General Hospital, Boston, MA

How should I choose between the direct oral anticoagulants (DOACs)?

Is central sleep apnea-Cheyne-Stokes respirations (CSA-CSR) in the setting of heart failure (HF) detrimental?

CSA-CSR is characterized by a crescendo-decrescendo pattern of 20-30 second hyperventilation followed by 10- 40 second hypopneas or apneas during exercise, wakefulness or stages 1 and 2 non-rapid eye movement sleep (1,2).

CSA-CSR is associated with elevated pulmonary capillary wedge pressure, ventricular dilatation, atrial fibrillation, and increased central and peripheral chemosensitivity to arterial C02 levels (1).

In contrast to obstructive sleep apnea whose detrimental impact is widely accepted, CSA-CSA has not consistently been shown to be associated with higher mortality rates.  Some even argue that it may be beneficial in HF by providing intrinsic positive end-expiratory pressure (PEEP), augmented stroke volume, avoidance of hypercapnic acidosis, attenuated sympathetic activity, bronchodilation and cyclic respiratory muscle rest, akin to those seen with episodic CPAP (2).

Wow! Is CSA-CSR nature’s CPAP? This is an interesting way of looking at CSA-CSR, and underscores the importance of addressing the underlying problem (e.g. HF) rather than the symptoms alone.

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References

1. Rosen D, Roux FJ, Shah N. Sleep and breathing in congestive heart failure. Clin Chest Med 2014, 35: 521–534. https://www.ncbi.nlm.nih.gov/pubmed/25156768

2. Naughton MT. Cheyne-Stokes respiration: friend or foe. Thorax 2012;67:357-360. http://thorax.bmj.com/content/thoraxjnl/67/4/357.full.pdf

Is central sleep apnea-Cheyne-Stokes respirations (CSA-CSR) in the setting of heart failure (HF) detrimental?

Is bridging anticoagulation necessary perioperatively in patients with non-valvular atrial fibrillation (AF)?

Until recently, there were no randomized-controlled trials (RCTs) available to help guide our decision.  A 2015 RCT, however, demonstrated that foregoing bridging anticoagulation was not inferior to bridging with low-molecular-weight heparin in patients with chronic or paroxysmal AF for the prevention of arterial thromboembolism and decreased the risk of major bleeding (1).  

It’s important to keep in mind the ineligibility criteria in this study before you consider not bridging perioperatively.  The following were listed as exclusion criteria in this study:

  • Mechanical valve
  • Stroke
  • Systemic embolism or transient ischemic attack within the previous 12 weeks
  • Major bleeding within the previous 6 weeks
  • Creatinine clearance < 30 ml/min
  • Platelet count < 100,000/ cubic ml
  • Planned cardiac, intracranial, or intraspinal surgery.                                                                                                                                     

Another important caveat of the BRIDGE study is that it included relatively few patients (<5%) with CHADS-2 score >4.

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Reference

  1. Douketis JD, Spyropoulos AC, Kaatz S, et al. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 2015 (published June 22 at NEJM.org).
Is bridging anticoagulation necessary perioperatively in patients with non-valvular atrial fibrillation (AF)?