Atrial fibrillation pharmacological treatment

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Synonyms and related keywords: AF, Afib, fib

Pharmacological treatment of atrial fibrillation
The two main goals in managing the patient with atrial fibrillation are:


 * 1) Prevent hemodynamic instability due to a low cardiac ouptut associated with poor ventricular filling as a result of rapid and chaotic contractions of the atrium. Rhythm control via antiarrhytmics is used to reduce the risk of developing recurrent atrial fibrillation, and rate control is used to reduce the heart rate when atrial fibrillation dues occur. If hemodynamic collapse has or is about to occur, then  immediate cardioversion may be indicated.
 * 2) Prevent embolic stroke. Anticoagulation with antiplatelets such as aspirin and/or clopidogrel or antithrombins such as warfarin or dabigatran are used to reduce the risk of embolic stroke.

The primary factors determining atrial fibrillation treatment are duration and evidence of hemodynamic instability. Cardioversion is indicated with new onset AF (for less than 48 hours) and with hemodynamic instability. If rate and rhythm control cannot be maintained by medication or cardioversion, electrophysiological studies with pathway ablation may be required.

Electrical & mechanical dissociation
Despite the restoration of sinus rhythm on the ECG following cardioversion (either spontaneous, pharmacologic or electrical or after radiofrequency catheter ablation of atrial flutter), in some patients there is a persistent lack of atrial contractility. This state is known as electrical mechanical dissociation and may be sue to mechanical stunning in the atrium and the atrial appendage. The lack of atrial contraction can be diagnosed on echocardiography by the appearance of spontaneous echo contrast. In general, the longer the patient was in atrial fibrillation, the longer the time it takes for the recoery of atrial mechanical function. The period of recovery can be quite variable, and it can take several weeks in total. Recovery of mechanical function can be delayed for several weeks, depending in part on the duration of AF before restoration of sinus rhythm   This kind of electrical mechanical dissociation may explain in part the observation that some patients develop thromboembolic events following cardioversion despite the fact that they had no visible left atrial clot on TEE. It has been hypothesized that the low shear state and turbulent nature of left atrial hemodynamics during this period leads to the development of clot which then embolizes once there is restoration of sufficient mechanical force. It is in part due to the presence of atrial mechanical dissociation and the risk of clot formation and embolization that oral anticoagulation is recommended for 3 to 4 weeks following successful electrical cardioversion in patients in whom the duration of Afib is unknown or in whom the duration of atrial fibrillation has been documented to be longer than 48 hours. Among patients in whom the duration of atrial fibrillation is less than 48 hours, the necessity for anticoagulation is not as clear, although it should be noted that stroke has been observed in these patients as well. No matter what the duration of atrial fibrillation, if a patient becomes hemodynamically unstable, this is an indication for immediate cardioversion.

New diagnosed or First Episode of Atrial Fibrillation
In patients who have self-limited episodes of paroxysmal AF, antiarrhythmic drugs to prevent recurrence are usually unnecessary, unless AF is associated with severe symptoms related to hypotension, myocardial ischemia, or HF. Whether these individuals require longterm or even short-term anticoagulation is not clear, and the decision must be individualized for each patient based on the intrinsic risk of thromboembolism.

Vagally mediated Atrial fibrillation
Disopyramide or flecainide

Adrenergically induced Atrial Fibrillation
Beta blockers (sotalol)

Congestive Heart Failure
amiodarone or dofetilide to maintain sinus rhythm.

Anticoagulation
Patients with atrial fibrillation, even lone atrial fibrillation without other evidence of heart disease, are at increased risk of stroke during long term follow up. A systematic review of risk factors for stroke in patients with nonvalvular atrial fibrillation concluded that a prior history of stroke or TIA is the most powerful risk factor for future stroke, followed by advancing age, hypertension, diabetes. The risk of stroke increases whether the lone atrial fibrillation was an isolated episode, recurrent, or chronic. The risk of systemic embolization (atrial clots migrating to other organs) depends strongly on whether there is an underlying structural problem with the heart (e.g. mitral stenosis) and on the presence of other risk factors, such as diabetes and high blood pressure. Finally, patients under 65 are much less likely to develop embolization compared with patients over 75. In young patients with few risk factors and no structural heart defect, the benefits of anticoagulation may be outweighed by the risks of hemorrhage (bleeding). Those at a low risk may benefit from mild (and low-risk) anticoagulation with aspirin (or clopidogrel in those who are allergic to aspirin). In contrast, those with a high risk of stroke derive most benefit from anticoagulant treatment with warfarin or similar drugs.

In the United Kingdom, the NICE guidelines recommend using a clinical prediction rule for this purpose. The CHADS/CHADS2 score is the best validated clinical prediction rule for determining risk of stroke (and therefore who should be anticoagulated); it assigns points (totaling 0-6) depending on the presence or absence of co-morbidities such hypertension and diabetes. In a comparison of seven prediction rules, the best rules were the CHADS2 which performed similarly to the SPAF and Framingham prediction rules.

To compensate for the increased risk of stroke, anticoagulants may be required. However, in the case of warfarin, if a patient has a yearly risk of stroke that is less than 2%, then the risks associated with taking warfarin outweigh the risk of getting a stroke.

Acute anticoagulation
If anticoagulation is required urgently (e.g. for cardioversion), heparin or similar drugs achieve the required level of protection much quicker than warfarin, which may take several days to reach adequate levels.

In the initial stages after an embolic stroke, anticoagulation may be risky, as the damaged area of the brain is relatively prone to bleeding (hemorrhagic transformation). As a result, a clinical practice guideline by National Institute for Health and Clinical Excellence recommends that anticoagulation should begin two weeks after stroke if no hemorrhage occurred.

Chronic anticoagulation
Among patients with "non-valvular" atrial fibrillation, anticoagulation with warfarin can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. . There is evidence that aspirin and clopidogrel are effective when used together, but the combination is still inferior to warfarin.

Warfarin treatment requires frequent monitoring with a blood test called the international normalized ratio (INR); this determines whether the correct dose is being used. In atrial fibrillation, the usual target INR is between 2.0 and 3.0 (higher targets are used in patients with mechanical artificial heart valves, many of whom may also have atrial fibrillation). A high INR may indicate increased bleeding risk, while a low INR would indicate that there is insufficient protection from stroke.

An attempt was made to find a better method of implementing warfarin therapy without the inconvenience of regular monitoring and risk of intracranial hemorrhage. A combination of aspirin and fixed-dose warfarin (initial INR 1.2-1.5) was tried. Unfortunately, in a study of AF patients with additional risk factors for thromboembolism, the combination of aspirin and the lower dose of warfarin was significantly inferior to the standard adjusted-dose warfarin  (INR 2.0-3.0), yet still had a similar risk of intracranial hemorrhage.

Elderly patients
The very elderly (patients aged 75 years or more) may benefit from anticoagulation provided that their anticoaguation does not increase hemorrhagic complications, which is a difficult goal. Patients aged 80 years or more may be especially susceptible to bleeding complications, with a rate of 13 bleeds per 100 person-years. A rate of 13 bleeds per 100 person years would seem to preclude use of warfarin; however, a randomized controlled trial found benefit in treating patients 75 years or over with a number needed to treat of 50. Of note, this study had very low rate of hemorrhagic complications in the warfarin group.

Maintenance of sinus rhythm
The mainstay of maintaining sinus rhythm is the use of antiarrhythmic agents. Recently, other approaches have been developed that promise to decrease or eliminate the need for antiarrhythmic agents.

Antiarrhythmic agents
The anti-arrhythmic medications often used in either pharmacological cardioversion or in the prevention of relapse to AF alter the flux of ions in heart tissue, making them less excitable, setting the stage for spontaneous and durable cardioversion. These medications are often used in concert with electrical cardioversion.

Further Readings

 * Fuster V, Rydén LE, Cannom DS, et al (2006). "ACC/AHA/ESC 2006 Guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society". Circulation 114 (7): e257-354. doi:10.1161/CIRCULATIONAHA.106.177292. PMID 16908781.
 * Estes NAM 3rd, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS, McNamara RL, Messer JV, Ritchie JL, Romeo SJW, Waldo AL, Wyse DG. ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with non valvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Performance Measures for Atrial Fibrillation). Circulation 2008; 117:1101–1120

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