ATRIAL FIBRILLATION


See also "Cerebrovascular Disease"

I. Pathophysiology and classification

  1. 350-500 atrial impulses/minute; irregular and slower ventricular response rate (usually 140-180 without tx)
  2. Can be associated with Ashmann's phenomenon: aberrant conduction of an impulse after a normal impulse following a pause; usually shows a RBBB pattern; arises from increased refractory period of bundle branches, R>L, after the pause
  3. Subcategories
    1. "Lone" AF: AF without other detectable cardiovascular disease (including hypertension or cardiac anomalies e.g. left atrial enlargement) or pulmonary disease and age < 60yo
    2. "Nonvalvular" AF: AF without severe mitral valve stenosis or regurgitation or history repair or replacement of the mitral valve

II. Risk factors

  1. Advanced age
  2. Rheumatic mitral valve disease
  3. CAD
  4. Cardiomyopathy
  5. Thyrotoxicosis
  6. EtOH lowers threshold; cocaine can cause
  7. Pulmonary embolus
  8. Hypoxia
  9. Sepsis
  10. Pericarditis
  11. Atrial myxoma

III. Clinical features

  1. Can be asymptomatic but often have palpitations; syncope can occur
  2. Associated with increased risk of embolic CVA (see below)
  3. Other complications include heart failure due to tachycardia-mediated cardiomyopathy

IV. Evaluation of a patient with newly-diagnosed AF

  1. Cardiac enzymes
  2. Thyroid function tests
  3. Testing for drugs of abuse if suspicion is present
  4. BUN/Cr, LFTs, K, glucose
  5. ECG for rhythm and ischemic changes
  6. Echocardiography to evaluate valvular and ventricular function

V. Management

  1. Rate control
  1. Indicated if tachycardia is persistent; urgently indicated if tachycardia is causing severe symptoms or hemodynamic instability (though if hemodynamically unstable, cardiology is first choice-see below)
  2. May reduce risk of tachycardia-mediated cardiomyopathy and thus heart failure in patients with AF
  3. "Lenient" rate control with target resting HR of < 110 beats/minute was associated with no sig. diff. in incidence of cardiovascular complications as "strict" rate control (with target HR < 80 BPM) in one clinical trial (cited in Core Content review)
  4. Specific treatments-If giving IV, monitor heart rate and BP closely
    1. Nondihydropyridine calcium-channel blockers, e.g. verapamil 0.075-0.15mg/kg over 2-3min or 80-120mg PO Q8h; diltiazem IV 0.25mg/kg over 20min, then IV gtt 5-15mg/h IV for up to 24h
      1. Avoid if early repolarization (e.g. Wolff-Parkinson-White) syndromes are suspected
    2. Beta-blockers, e.g. propanolol 0.025-0.1mg/kg IV, then 10-60mg PO Q6h; esmolol 50-200ug/kg/min; May help to convert to SR as well as controlling rate
    3. Digoxin IV (0.25-0.75 or 0.5 PO x1 then 0.26 PO Q6-8h, max 1mg total dose) to control rate to 70-90/min-Check serum [K], don't give if hypokalemic
  5. AV nodal ablation (see below) could be considered a form of rate control
  1. If rate control is not indicated or does not result in spontaneous reversion to sinus rhythm, must choose between approaches of "rhythm control" (i.e. attempt to convert to and maintain sinus rhythm) vs. "rate control" (i.e. leave in AF with treatment to control heart rate and with anticoagulation; see section below re: comparison between them)
  1. Rhythm control
  1. Not associated with reduced mortality, and medications used for this purpose have risk of adverse effects, so generally reserved for patients for whom the symptoms are troublesome.
  2. DC electrocardioversion
  1. Generally considered to be urgently indicated in pts with recent-onset AF with rapid ventricular response and evidence of acute myocardial ischemia, symptomatic hypotension, or heart failure.
  2. Better success with <6mos AF, small LA, MS rather than MR if mitral valve disease exists
  3. Worse success if CHF with NYHA Class III or worse or age >56yo
  4. Can repeat cardioversion if AF recurs after cardioversion; if so, some recommend adding an antiarrhythmic drug prophylactically
  5. Usual approach is before attempting conversion, anticoagulate if AF may have been present >48h (to INR 2.0-3.0 x 3wks and continue 4wks post-conversion)
  6. Use of transesophageal echocardriography (TEE) rule out intra-atrial thrombus and clear for immediate cardioversion
    1. 1222 pts w/AF > 48h all underwent DC cardioversion, randomized to prior tx with warfarin x 3wks vs. (Heparin IV x 24h OR warfarin x 5d then TEE and cardioversion if no thrombi seen; if thrombi seen, warfarin x 3wks then DC cardioversion); all pts got warfarin x 4wks after cardioversion. Rates of embolic events at 8wks were 0.8% in TEE group and 0.5% in conventional group (nonsig.) and total mortality slightly higher in TEE group (2.4% vs. 1.0%, nonsig.); but hemorrhagic events sig. less common in TEE group (2.4% vs. 1.0%). (NEJM 344:1411, 2001--JW)
    2. In an uncontrolled series of 533 pts with AF > 48h pre-tx'd with heparin to therapeutic PTT; 463 pts had no thrombus on TEE and were cardioverted; only 1 had a clinically significant thromboembolic event; among 278 pts followed x 1y, recurrence rate of AF was 41% for those who had had AF x < 3wks at time of cardioversion vs. 58% for those with AF lasting > 3wks at time of cardioversion (sig.) (AM. J. Med. 110:694, 2001--JW)
  7. Use of TEE rule out intra-atrial thrombus in patients who have been anticoagulated to therapeutic INR x 3wks: In one nonrandomized study (using two consecutive cohorts), a strategy of doing TEE before cardioversion and postponing cardioversion if left atrial thrombus was detected was NOT ass'd with any difference in post-cardioversion embolic events (JACC 39:1436, 2002--abst)
  1. Antiarrhythmic medication for rhythm control-Both IA's and Sotalol may actually increase mortality with long-term use for maintenance of sinus rhythm in AF (Am. J. Cardiol. 83:1629, 1999--AFP)
  1. Class IA antiarrhythmics
    1. Quinidine (e.g. 200mg PO Q2h x 5 on day 1, 300mg Q2h x 5 on day 2, with 1st dose 7am & last dose 3pm; or 200mg Q4h x 24h then 300mg Q4h x 24h); if doesn't convert after 48h quinidine, use electrocardioversion. Quinidine causes much diarrhea and can cause torsades des pointes
    2. Procainamide--alternative first-line to Quinidine
    3. Disopyramide--3rd-line; has a good side-effect profile
  1. Class IC antiarrhytmics
    1. Propafenone (2nd-line)
    2. Flecainide (3rd-line)--use only if no structural heart disease
  1. Class II antiarrhythmics (beta-blockers)
  1. 394 pts successfully undergoing DC Cardioversion for AF randomized to Metoprolol XR 100-200mg/d vs. placebo. 6mo relapse rate was sig. less in the metoprolol group (49% VS. 60%) (JACC 36:139, 2000--JW)
  1. Class III antiarrhythmics
    1. Sotalol (combined class II/III)
    2. Amiodarone (Cordarone)-Appears more effective at maintaining sinus rhythm than either Sotalol or Propafenone
      1. 70 pts with symptomatic AF (chronic or paroxysmal) successfully converted in the ER randomized to amiodarone (loading with 800-1600mg/d x 7-14d then taper to maintenance of 200/d) vs. sotalol (80mg BID titrated to max of 360 BID; dose lowered if pt noted side fx or QTc was found to be > 500ms). At 1y f/u, 70% of amiodarone group c/w 40% of sotalol group were still in sinus rhythm (summary doesn't say if sig.); results not affected by age, sex, LA size, or underlying cardiac disease. MI < 1wk prior, decreased LVEF, unstable renal or hepatic disease, & hyperthyroidism were exclusion criteria (Am. J. Cardiol. 81:995, 1998--AFP)
      2. 403 pts with at least 1 symptomatic episode of AF in previous 6mos randomized to amiodarone, sotalol, or propafenone. Over mean 15mo f/u, amiodarone group had sig. fewer recurrences of AF than combined incidence in sotalol & propafenone groups (35% vs. 63%; no diff. between sotalol & propafenone). Amiodarone had sig. fewer CVA's but no sig. diff. in mortality (NEJM 342:913, 2000--JW)
      3. Possible adverse effects include cataract formation and pulmonary fibrosis
      4. As of 2012, use for atrial fibrillation generally only in symptomatic patients with HF and low LVEF
    3. Dofetilide-Associated with torsades de pointes (risk about 0.8%, higher in pts with LV dysfunction). Recc'd to start in-hospital with 72h of cardiac monitoring. Start at 500ug BID, less in pts with renal failure or pts who develop QTc > 500msec during tx.
    4. Azimilide-Associated with torsades des pointes
  1. Antiarrhythmics with mixed properties
    1. Dronedarone (Multaq) 400mg BID with meals-Less effective, but also less toxic, than amiodarone
      1. Has properties of antiarrhythmics class I-IV
      2. Chemically similar to amiodarone but has less tissue absorption and may be less toxic with long-term use (i.e. no association with thyroid, pulmonary, or liver disease)
      3. May worsen heart failure
      4. May cause bradycardia, prolongation of QT interval, nausea, diarrhea, rash, and elevated serum Cr levels.
      5. In a meta-analysis of nine trials (4 dronedarone vs. placebo, 4 amiodarone vs. placebo, 1 head-to-head), incidence of recurrent AF was sig. lower with amiodarone (OR 0.49) but amiodarone recipients had sig. higher incidence of adverse effects requiring drug discontinuation (OR 1.8) and nonsig. higher mortality (OR 1.6) (J. Am. Coll. Cardiol. 54:1089, 2009-JW)
      6. In a study in 504 pts with atrial fibrillation requiring cardioversion randomized to dronedarone vs. amiodarone, over median 7mo f/u, dronedarone group had higher incidence of AF recurrence (64% vs. 42%) but lower incidence of drug discontinuation due to adverse effects (5% vs. 11%) ("DIONYSOS" studi; J. Cardiovasc. Electrophysiol. 21:597, 2010-JW)  

      7. In a study in 4,628 pts with atrial fibrillation and one of (HTN, DM, prior CVA or TIA, left atrial enlargement, or LVEF of 40% or less) randomized to dronedarone 400mg BID vs. placebo, over mean 21mo f/u, incidence of (first hospitalization for a cardiac event or death from any cause) was sig. lower in dronedarone group (32% vs. 39%) though no sig. diff. in mortality was noted.  Dronedarone recipients had sig. higher incidence of bradycardia, QT prolongation, QI complaints, and elevated serum Cr, but not in evident pulmonary, liver, or thyroid doxicity ("ATHENA" trial; NEJM 360:668, 2009-JW)

  2. A comparison of antiarrhythmics for cardioversion of AF--115 pts with AF onset < 24h previously, randomized to sotalol vs. amiodarone vs. digoxin; reversion to sinus rhythm at 48h was 88%, 77%, and 58%, respectively; difference between first two and dig was sig. (Ann. Emerg. Med. 36:1, 2000--JW)
  3. In a meta-analysis of 44 randomized studies of anti-arrhythmic drugs for maintaining sinus rhythm, AF recurrence was sig. lower with type IA, IC, and III (except dronedarone) antiarrhythmics c/w controls; amiodarone was sig. better than IA drugs.  Mortality was sig. higher among IA recipients than controls.  (Arch. Int. Med. 166:719, 2006--JW)
  1. Rate-control vs. rhythm-control as strategies for long term management of AF
    1. Most randomized trials (with one exception using dronedarone) have failed to show an advantage of one over the other; Rate control may actually be associated with better outcomes in patients > 65yo
    2. Patients who remain symptomatic despite adequate rate control are generally considered candidates for rhythm control
    3. 252 pts 18-75yo with symptomatic AF 7-360d in duration randomized to rate control (diltiazem) vs. rhythm control (pharmacologic and/or DC cardioversion); all pts received anticoagulation.  At 1y, there were no sig. diffs. in % of pts still symptomatic or quality of life scores between the two groups.  Pts in rhythm-control group had sig. higher incidence of drug side effects (64% vs. 47%) (Pharmacological Intervention in Atrial Fibrillation ("PIAF") Trial; Lancet 356:1789, 2000--AFP)
    4. 3060 pts with onset of AF < 6mos previously and (age > 65yo or other risk factors for CVA) randomized to rhythm control (anti-arrhythmic drugs and/or DC cardioversion) vs. rate control (with beta-blockers, Ca-blockers, and/or digoxin); all pts also received warfarin.  Over mean 3.5y f/u, no sig. diff. in all-cause mortality; rhythm-control group had sig. higher rates of hospitalization and drug discontinuation due to adverse effects (NEJM 347:1834, 2002--JW)
    5. 522 pts with recurrent or persistent AF after attempted cardioversion randomized to rhythm control vs. rate control (similar interventions to study above); over mean 2.3y f/u, rhythm-control group had nonsig. higher incidence of (CV death, heart failure, thromboembolism, bleeding, need for pacemaker, or severe drug side f/x) than rate-control group (22.6% vs. 17.2%) (NEJM 347:1883, 2002--JW)
    6. In a secondary analysis of a study in 665 pts with persistent atrial fibrillation randomized to amiodarone, sotalol, or placeo, over 1y f/u, those pts who were in sinus rhythm had sig. better quality of life scores and sig. lower symptom scores than those still in AF.  In the already-published report on this study (NEJM 352:1861, 2005), data was presented showing that amiodarone & sotalol were equally efficacious at converting to sinus rhythm but that amiodarone was assocaited with sig. lower incidence of recurrence of AF  ("Sotalol Amiodarone Atrial Fibrillation Efficacy Trial ("SAFE-T"), presentation by D.r Steven Singh at the Heart Rhythm Society, reported in Family Practice News, July 2005)
    7. In a study in 192 women and 330 men with persistent atrial fibrillation randomized to rate control (with digoxin, beta-blockers, and calcium-blockers) vs. rhythm control (using sotalol, class IC anti-arrhythmic drugs, and amiodarone), over mean 2.3y f/u, among women, incidence of (cardiovascular death or other cardiovascular event) was sig. higher in rhythm control group (33% vs. 11%); among men there was no sig. diff. ("Rate Control versus Electrical Cardioversion" ("RACE") Study; J. Am. Coll. Cardiol. 46:1298, 2005--JW)
    8. A randomized trial using dronedarone showed a reduction in cardiovascular (but not overall) mortality (NEJM 360:668, 2009, cited in Core Content review)
  2. RF catheter ablation
    1. Usually focuses on arrhythmogenic triggers in the pulmonary veins, or electrical pathways between those areas and the left atrium
    2. If the AV node is the target of ablation, requires implantation of a permanent ventricular pacemaker
    3. Shown to be associated with improvement in LVEF and symptoms in pts with AF and Heart Failure in nonrandomized studies (NEJM 351:2373, 2004--JW)
    4. Traditionally considered 2nd-line if no response to cardioversion or drugs, because of risk
    5. Pre-anticoagulate for at least 1mo; switch to unfractionated or low-molecular-weight heparin for the procedure itself and continue anticoagulation for at least 2mos after ablation.
    6. Approximately 40% of patients episodic atrial fibrillation for several weeks after ablation, so it is recommended to continue anticoagulation for at least 2mos post-procedure, longer if other cardiovascular risk factors are present (e.g. indefinite anticoagulation if pt has a "CHADS" score of 2 or more (Congestive heart failure, Hypertension, Age >75 years, Diabetes, previous Stroke or TIA)
    7. Risk factors for failure of ablation (total failure or initial success but recurrence of AF): Persistent AF, longer duration of AF, older age, underlying heart disease
    8. 1-2% risk of life-threatening complications, including CVA, cardiac rupture and cardiac tamponade.
    9. In a study in 198 pts with paroxysmal atrial fibrillation who had failed treatment with antiarrhythmic drugs randomized to further antiarrhythmic drug therapy (flecainide, amiodarone, or sotalol) vs. circumferential pulmonary-vein ablation.  Over 1y, incidence of AF recurrence was sig. lower in ablation group (22% vs. 86%) (J. Am. Coll. Cardiol. 48:2340, 2006--JW)
    10. In a study in 167 pts with AF not responsive to at least one antiarrhythmic drug randomized to antiarrhythmic drug therapy vs. catheter ablation, after 9mos, incidence of treatment failure was sig. lower with catheter ablation group (33% vs. 84%) and mean uality-of-life scores were higher in catheter ablation recipients (JAMA 303:333, 2010-abst)
  1. Implantable automatic cardioverter (Circ. 98:1651, 1998--JW; Circ. 102:1407, 2000--JW)
  2. Angiotensin Receptor Blockers to reduce risk of adverse outcomes in patients with atrial fibrillation
    1. In a study in 9,016 pts with atrial fibrillation with at least two episodes in prior 6mos randomized to irbesrtan vs. placebo, over median 4.5y f/u, there was no sig. diff. in incidence of (MI, CVA, or vascular death) or recurrent atrial fibrillation (for sthose pts who were in sinus rhythm at study enrollment ("ACTIVE I" trial; NEJM 364:928, 2011-JW).

VI. Risk of CVA in pts with Atrial Fibrillation

  1. Estimating risk of CVA in patients with AF
    1. Overall RR for CVA is about 5.0 in pts with AF compared with patients without AF
    2. Risk in intermittent AF is similar to that in sustained AF (JACC 35:183, 2000--AFP)
    3. Patients s/p successful cardioversion still have a high likelihood of recurrence of AF, which may be asymptomatic, so should be treated the same as patients with known chronic AF in consideration for antithrombotic treatment.
    4. "CHAD2DS2-VASc" score for estimating CVA risk in patients with nonvalvular AF

Risk Factor Score
Congestive heart failure or left ventricular dysfunction 1
Hypertension 1
Age > 75y 2
Age 65-74y 1
Diabetes mellitus 2
History of CVA, TIA, or thromboembolism 1
Vascular disease (h/o MI, peripheral arterial disease, or aortic plaque) 1
Female gender 1
    1. Risk factors for CVA in pts with AF (per ACC/AHA guidelines; JACC 48:854, 2006--JW)
      1. "High Risk" factors
        1. Prior cerebral ischemic events (CVA, TIA, or embolism)
        2. Mitral Stenosis
        3. Prosthetic heart valve
      2. "Moderate Risk" factors
        1. Age > 75yo
        2. Hypertension
        3. Diabetes mellitus
        4. Heart Failure
        5. LVEF < 35%
  1. Antithrombotics to reduce risk of CVA in pts with atrial fibrillation: options include aspirin, warfarin, and non-warfarin oral anticoagulants
  1. Comparisons of  Warfarin  vs. Antiplatelets
    1. In a meta-analysis of 5 randomized trials involving total 3,298 pts with AF, anticoagulation, compared with aspirin was ass'd with nonsignificantly lower risks for CVA death (OR 0.74), vascular death (OR 0.86), and combined fatal & nonfatal events (OR 0.79) (BMJ 322:321, 2001--JW)
    2. In a meta-analysis of 6 studies (total n = 4052) of warfarin vs. aspirin in pts with nonrheumatic AF, warfarin was ass'd with sig. lower incidence of CVA (HR 0.55) and cardiovascular events (HR 0.71), but sig. higher incidence of major bleeding (HR 1.71).  Pts with paroxysmal AF had similar risk reductions for ischemic CVA (HR 0.32); there were no sig. diffs in overall mortality.  Greatest benefit in CVA reduction if >75yo, male, prior cerebrovascular event, or diabetic (JAMA 288:2441, 2002--abst)
    3. In a study in 6,706 pts with atrial fibrillation and at least one stroke risk factor randomized to warfarin (adjusted to target INR 2.0-3.0) vs. (clopidogrel 75mg/d + aspirin 75-100mg/d), over median 1.3y f/u, the warfarin group had sig. lower incidence of CVA (1.4%/yr vs. 2.4%/yr) and of (CVA, non-CNS embolism, MI, or vascular death; 3.9% vs. 5.6%); no sig. diff. in incidence of major bleeding ("ACTIVE" Trial; Lancet 367: 1903, 2006--JW)
  2. Comparisons of Warfarin + Antiplatelets vs. Warfarin alone
    1. Low-dose unadjusted warfarin (adjusted at start to give INR 1.2-1.5) plus ASA 325mg QD associated with sig. more ischemic CVA than adjusted-dose warfarin (INR 2.0-3.0); no sig. diff in risk of major hemorrhage (Lancet 348:633, 1996-JW)
  3. Comparisons of different antiplatelets
    1. In a study in 7,554 pts pts with atrial fibrillation + at least one CVA risk factor who were considered unsuitable for warfarin, all of whom received aspirin 75-100mg/d, randomized clopidogrel 75mg/d vs. placebo, over median 3.6y f/u, incidence of (CVA, MI, non-CNS systemic embolism, or vascular death) was sig. lower in the clopidogrel group (6.8% vs. 7.6%)  ("ACTIVE A" Trial; NEJM 360:2066, 2009-JW)
  4. Studies comparing various degrees of anticoagulation with Warfarin
    1. In a case-control study, INR < 2.0 ass'd with increased risk of CVA c/w INR of 2.0; INR > 2.0 not ass'd with add'l benefit (NEJM 335:540, 1996-JW)
  5. Non-warfarin oral anticoagulants for CVA prophylaxis in patients with atrial fibrillation
    1. In a study in 5,599 pts with atrial fibrillation and at least one additional CVA risk factor AND a contraindication to warfarin, randomized to apixaban 5mg BID vs. ASA 81-324mg/d (dosing left to physician discretion),over mean 1.1y f/u, the yearly incidence of (CVA or systemic embolism) was sig. lower in apixaban pts (1.6% vs. 3.7%) as was the incidence of (CVA, systemic embolism, MI, vascular death, or major bleeding) (5.3% vs. 7.2%) with no sig. diff.in the incidence of major bleeding ("AVERROES" trial; NEJM 2/10/2011; e-publication ahead of printing; http://www.nejm.org/doi/full/10.1056/NEJMoa1007432).
    2. In a study in about 14,000 pts with nonvalvular atrial fibrillation randomized to warfarin vs. rivaroxaban 20mg/d, over mean 19mo f/u, rivaroxaban pts had lower incidence of (CVA or systemic emboli) vs. warfarin pts (1.71 vs. 2.16 events/100 pt-years); no diff. in incidence of major bleeding. ("ROCKET AF" trial; presented at American Heart Association meeting 11/2010-JW)
    3. In a study in 18,113 pts with AF and at least one of (prior CVA, low LVEF, or age > 75yo) randomized to dabigatran 110mg BID vs. 150mg BID vs. warfarin, over median 2y f/u ("RE-LY" trial; NEJM e-publication 8/30/09 (10.1056/NEJMoa905561-FP News)):
      1. Dabigatran 110mg pts had no sig. diff. in incidence of CVA and sig. lower incidence of major bleeding events c/w warfarin
      2. Dabigatran 150mg pts had sig. reduction in incidence of (CVA or systemic embolism) with no sig. diff. in incidence of major hemorrhage c/w warfarin
    4. In a subgroup analysis of data from the RE-LY trial, in 3,623 pts with h/o CVA or TIA, over 2y median f/u, the annual incidence of (CVA or systemic embolism) was not sig. diff. between warfarin group and either the 110mg or the 150mg dabigatran groups; however, both doses of dabigatran were associated with sig. lower incidence of hemorrhagic CVA. Incidence of major bleeding was sig. lower in 110mg dabigatran group c/w warfarin (RR 0.66) but no sig. diff. between 150mg dabigatran group and warfarin (Lancet Neurol. 9:1157, 2010-JW)
  6. Comparisons of Warfarin vs. Ximelagatran
    1. In a trial of 254 pts with non-valvular atrial fibrillation and at least one other CVA risk factor (HTN, age > 75yo, prior CVA or TIA, LV dysfunction, or ((DM or CAD) + age > 65yo) randomized to ximelagatran 20-60mg/d  vs. adjusted-dose warfarin (target INR 2.0-3.0) x 12wks, there were no systemic embolic events in either group and no sig. diff. in incidence of adverse events; 4% of ximelagatran pts (and none of the warfarin pts) had transient transaminase elevations ("SPORTIF-II" trial, JACC 41:1445, 2003--JW)
    2. In a trial of 3410 pts with nonvalvular atrial fibrillation and one other CVA risk factor (see summary of SPORTIF-II above) randomized to Ximelagatran 36mg BID vs. adjusted-dose warfarin (target INR 2.0-3.0); over mean 17mo f/u, incidence of (stroke or systemic embolism) was nonsig. lower in ximelagatran group (1.6% vs. 2.3%); no diff. in incidence of death or major bleeding; minor bleeding sig. less common in ximelagatran recipients.  6% of Ximelagatran recipients had ALT elevations but in most of those pts normalized w/continued use ("SPORTIF-III trial"--Lancet 362:1691, 2003--JW)
    3. In a study of 3,922 pts with nonvalvular atrial fibrillation randomized to ximelagatran 36mg BID vs. warfarin (to INR 2.0-3.0), over mean 20mo f/u, incidence of (any CVA or systemic embolic event) and major bleeding were not sig. diff in the two groups, though total bleeding was sig. lower with ximelagatran (37% vs. 47%/yr) (JAMA 293:690, 2005--abst)
  1. Low risk patients may not need anticoagulation
    1. In a prospective cohort uncontrolled study of 892 "low risk" pts (nl LVEF and no h/o CHF; SBP < 160 mm Hg; no prior ischemic cerebral event or embolic episode; age < 75yo if female; no prosthetic heart valves, mitral stenosis, or other conditions requiring anticoagulation) with AF tx'd with ASA 325mg/d and no warfarin w/avg f/u 2y; risk of CVA or cerebral embolic events was 2.2%/yr; rate of disabling ischemic CVA was 0.8%/yr; rate of major bleeding events was 0.5%/yr (JAMA 279:1273, 1998--JW)
  1. Recommendations from European Society of Cardiology (Eur. Heart J. 31:2369, 2010, cited in Core Content review)
    1. If CHAD2DS2-VASc score = 0, options include no treatment (preferred) or aspirin 75-325mg/d
    2. If CHAD2DS2-VASc score = 1, options include oral anticoagulants (preferred) or aspirin 75-325mg/d
    3. If CHAD2DS2-VASc score > 1, oral anticoagulation indicated
  1. Recommendations from ACC/AHA (JACC 48:854, 2006--JW)
    1. If pt has no "risk factor" (see above), ASA
    2. If has 1 "moderate risk factor", ASA or warfarin
    3. If has 2 or more moderate risk factors" or 1 or more "high risk factor" then warfarin

(Sources include Core Content Review of Family Medicine, 2012)