af is the most common cardiac arrhythmia , with an estimated risk of development during lifetime of 1 in 4 men and women with at least 40 years of age [ 1 - 3 ] . the clinical interest in this condition derives from the fact that it increases the risk of mortality by two - fold , of congestive heart failure by three - fold , and of stroke by five - fold . the treatment of af has two targets : the prevention of the thrombo - embolic complications and the reduction of symptoms and consequences related to the arrhythmia by rhythm or rate control therapies . vitamin k antagonists reduced the relative risk of stroke by 64% , corresponding to an absolute annual risk reduction in all strokes of 2.7% . it is universally recognized that the oral anticoagulation ( oac ) is the mainstream therapy for the reduction of thrombo - embolic complications related to af . several scores have been developed to identify patients with high risk of thrombo - embolic events and those who need anticoagulation . however , given the high efficacy of oac and the enormous consequences of strokes , it would be better to change our approach from the identification of many patients who need oac to the research of the few patients who do not need oac . cardiologists should therefore consider the presence of af itself as an indication to anticoagulation therapy , unless the patient has a truly low risk . the latest european society of cardiology guidelines   suggest that , for the correct evaluation of patients with non - valvular af , the use of the cha2ds2-vasc  congestive heart failure / left ventricular dysfunction , hypertension , age of at least 75 ( doubled ) , diabetes , stroke ( doubled)-vascular disease , age 65 to 74 , and sex category ( female)score   is more sensible compared with the previously used chads2 score . patients with af who have at least one stroke risk factor are recommended to receive oac with either well - controlled vitamin k antagonist therapy  international normalized ratio ( inr ) 2 - 3 , with more than 70% of time in the therapeutic range  or one of the new oral anticoagulants ( noacs ) . only patients with lone af who are less than 65 years old have very low absolute stroke rates and do not require oac . the oac usually revives in the physician 's mind the ghost of major bleeding ; this fear is the main reason for the frequent denial of such an effective therapy to a high number of patients . the guidelines suggest the assessment of the bleeding risk in all patients with af with the has - bled hypertension , abnormal renal / liver function , stroke , bleeding history or predisposition , labile inr , elderly ( e.g. age more than 65 years and frailty ) , drugs / alcohol concomitantly  score . the score should be used to balance the risk of stroke against potential major bleeding events ; however , a high - risk score should not exclude patients from oac , but favor the identification and correction of potentially reversible risk factors , such as uncontrolled blood pressure , concomitant use of aspirin / non - steroidal anti - inflammatory drugs , and labile inrs . in patients who are not candidates for oac the weapon used in this battle , however , appears not to be pathophysiologically adequate to the setting ; in fact , thrombi in patients with af are predominantly fibrin - rich ( the so - called  red clots  ) , while thrombi found in coronary artery lesions tend to be platelet - rich (  white clots  ) . therefore , such an effective therapy in athero - thrombotic vascular disease becomes of limited value in patients with af . the meta - analysis by hart et al .   reviewed seven randomized control trials evaluating the antithrombotic therapy for stroke prevention in non - valvular af ( 3990 participants in aspirin - only trials ) . the result was a reduction of risk of stroke with anti - platelet therapy compared with placebo by 19% ( 95% confidence interval [ ci ] 1% to 35% ) with a 95% ci that included zero ; this raises the possibility of non - significant clinical effect . aspirin has been frequently used in elderly patients , with the hope of fewer side effects . this belief was not confirmed by the birmingham atrial fibrillation treatment of the aged ( bafta ) trial , which randomly allocated patients over 75 years of age to receive oac with warfarin or 75 mg of aspirin daily ; in the oac group , the yearly risk of the primary endpoint ( disabling stroke , intracranial hemorrhage , or arterial embolism ) was 1.8% and significantly lower than the 3.8% obtained with aspirin ; warfarin treatment in the elderly was associated with a 52% relative risk reduction compared with aspirin . even when a second anti - platelet agent , such as clopidogrel in the active - w ( atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events ) trial , is added , the effect is clearly inferior to the one obtained by the oac treatment . following the hypothesis that double anti - platelet association was an effective replacement of oac , the active - a trial   randomized 7554 patients with af to aspirin plus clopidogrel or to warfarin . double anti - platelet therapy reduced the risk of stroke by 28% , but it increased the risk of major bleeding by 50% . with the advent of noacs , which promise the efficacy of standard oac without any increased risk of bleeding , it is not difficult to foresee that both aspirin and the double anti - platelet therapy for af will become obsolete or restricted to rare cases . noacs , in contrast to warfarin ( which blocks multiple active vitamin k - dependent coagulation factors ) , block the activity of one single step in the coagulation process . dabigatran acts as an oral direct thrombin inhibitor , while rivaroxaban and apixaban both inhibit factor xa . all noacs have shown non - inferiority in stroke and systemic embolism prevention , compared with warfarin . in the re - ly ( randomized evaluation of long - term anticoagulation therapy ) trial , dabigatran 150 mg bis in die ( twice a day  b.i.d . ) was superior to warfarin , with no significant difference in the safety endpoint of major bleeding ; the reduced dosage of 110 mg b.i.d . was non - inferior to warfarin , with 20% fewer major bleeds ; both dosages were associated with a non - significant increase of 28% in myocardial infarction . in the aristotle ( apixaban for reduction in stroke and other thrombotic events in atrial fibrillation ) trial , apixaban 5 mg b.i.d . reduced the primary endpoint of stroke or systemic embolism by 21% compared with warfarin , with a 31% reduction in major bleeding and a significant 11% reduction in all - cause mortality . edoxaban , a new factor xa inhibitor , has completed late - stage clinical assessment . a meta - analysis pooling more than 40,000 patients from four randomized controlled trials comparing noacs with warfarin has been recently published ; compared with warfarin , the noacs , as a class , reduced all - cause mortality by about 10% in the populations enrolled in the clinical trials . stroke and systemic embolic events were significantly reduced in patients receiving noacs ; the benefit was driven mainly by substantial protection against hemorrhagic stroke , while they had similar efficacy in the prevention of ischemic stroke . several trials in recent years tried to assess whether restoration of sinus rhythm offers any advantage compared with the strategy of rate control . although sinus rhythm restoration is theoretically supposed to be the best option , many studies such as piaf ( pharmacological intervention in atrial fibrillation ) , affirm ( atrial fibrillation follow - up investigation of rhythm management ) , race ( rate control versus electrical cardioversion for persistent atrial fibrillation ) , and staf ( strategies of treatment of atrial fibrillation )   failed to report any survival benefit from rhythm - control strategy . also , in the population of patients with heart failure , no clear benefit was demonstrated for this strategy . later  on treatment  analysis of the affirm trial showed that the presence of sinus rhythm is associated with a lower risk of death ; this analysis suggested that the adverse effects of anti - arrhythmic drugs ( aads ) overcome the beneficial effects of sinus rhythm restoration ; it is also conceivable that the efficacy of currently available aads is so limited and transient that any positive effect of sinus rhythm does not have enough time to develop . this raised the interest in other treatments , such as catheter ablation ( ca ) of af , whose effects are supposed to be more durable . wilber et al .   compared the efficacy of catheter ablation with aad treatment in treating symptomatic patients with paroxysmal af who had not responded to at least 1 aad ; the invasive treatment resulted in a longer time to treatment failure ( 66% of patients in the catheter ablation group remained free from protocol - defined treatment failure compared with 16% of patients treated with aad therapy ) during the 9-month follow - up period . the efficacy of ca is dependent on the type of af , the presence of cardiac structural heart disease , and co - morbidities . presence of left atrial scar is an independent predictor of arrhythmia recurrence after the ablation . magnetic resonance imaging studies demonstrated that recurrence rate after ca is directly related to the amount of left atrial scar : patients with minimal late gadolinium enhancement ( 8.0%  4.2% ) have fewer recurrences ( 14.0% ) compared with patients with moderate enhancement ( 21.3%  5.8% , recurrence rate = 43.3% ) and patients with extensive enhancement ( 50.1%  15.4% , recurrence rate = 75% ) . when confirmed by large population studies , the extension of left atrial scar can be included in the pre - operative assessment of af patients in order to reduce the number of procedures in patients with expected low efficacy . the best results of the ca procedure are actually obtained in patients with paroxysmal af in the absence of cardiac structural disease and co - morbidities [ 26 - 33 ] . in those patients , af is related to the presence of triggers in the pulmonary veins ( pvs ) ; therefore , pv isolation is the cornerstone treatment for patients with paroxysmal af [ 34,36 - 38 ] . in a recent meta - analysis of 19 studies , rates of single - procedure success for paroxysmal af ablation were 68.6% ( 95% ci 58.9% to 77.0% ) at 1 year , 61.1% ( 95% ci 49.8% to 71.2% ) at 3 years , and 62.3% ( 95% ci 39.8%to 80.5% ) at 5 years . the pooled 12-month success rate for paroxysmal af ablation after a single procedure was 66.6% ( 95% ci 58.2% to 74.2% ) ; it increased to 79.0% ( 95% ci 67.6% to 87.1% ) when multiple procedures were used ( average number of procedures : 1.45 ) . the most common cause of arrhythmia recurrence is reconduction across pv isolation ; nanthakumar et al .   found reconduction in 42 of 51 previously isolated veins in 15 patients with recurrent symptoms after a first ablation for paroxysmal af . in the experience of verma et al . , all veins were still isolated in 81% of patients undergoing a repeat procedure after the index ablation ; this rate dropped to 5% and 0% in the patients maintaining sinus rhythm on aads and in patients with arrhythmia despite aads . ablation has been performed for many years with the point - by - point approach with continuous catheter dragging during radiofrequency delivery or by repeated short - time radiofrequency shots . this approach is highly dependent on the operator 's skill and the contact between the tip of the catheter and the target tissue ; freedom from arrhythmia recurrences is best achieved when ablation lesions are placed with an average contact force ( cf ) of more than 20 g , and clinical failure is frequent with an average cf of less than 10 g . recently developed catheters allow pv isolation with one or a few shots of radiofrequency , cryo - energy , or laser pulses . medtronic pvac ( medtronic ablation frontiers , carlsbad , ca , usa ) and nmarq ( biosense webster , diamond bar , ca , usa ) catheters have a circular shape that fits with pulmonary veins ostia ; radiofrequency can be delivered simultaneously by a variable number of electrodes . the arctic front advance cardiac cryoablation catheter ( arctic front ; medtronic ) consists of a balloon that can be placed at each pv ostium in order to obtain pv occlusion ; ablation is then performed by cryo - energy . ma , usa ) is a visually guided laser ablation catheter with a variable - diameter balloon that accommodates a 2-fr endoscope ; it provides real - time visualization of the balloon contact and blood during the ablation . in a multicenter experience enrolling 200 patients with paroxysmal af , it showed an efficacy similar to that of radiofrequency ablation . reported major complications were cardiac tamponade ( 2% ) and phrenic nerve palsy ( 2.5% ) . pv isolation is still mandatory for the treatment of persistent and long - standing af . however , recurrent and chronic af induces progressive electrical and tissue structural remodeling , thus making af a self - perpetuating disease ; to interrupt this looping process , the ablation procedure in non - paroxysmal af patients usually requires some kind of substrate modification . three approaches were developed : linear lesions , complex fractionated atrial electrogram ( cfae ) ablation , and electrical rotor elimination . linear lesions have been applied on the left atria roof and on the mitral isthmus with the aim of preventing macro - re - entry - dependent arrhythmias ; several studies reported that additional lines improve the efficacy of the procedure . the downside of this approach becomes evident when the lines are not electrically continuous ; in those cases , atrial tachycardia frequently develops . in order to reduce macro - re - entry arrhythmias recurrences , the operator should validate the presence of a bidirectional conduction block across all ablation lines . cfae ablation was proposed by nademanee et al . ; it can be used alone or in combination with pv isolation . manifest controversies still exist concerning the usefulness of this approach because it frequently requires wide left atrial ablation , and it is hampered by a high post - procedural atrial tachycardia rate . in the rasta ( randomized ablation strategies for the treatment of persistent atrial fibrillation ) study , 1-year af - free survival was significantly lower in patients treated with the standard approach ( pv isolation + ablation of documented non - pv triggers identified by a standard stimulation protocol ) plus cfae ablation compared with the standard approach alone or the standard approach combined with the empirical ablation at common non - pv trigger sites . recent evidence demonstrated that electrical rotors have a key role in sustaining af in humans . a computational approach was used to analyze the repolarization and conduction dynamics with the aim of reconstructing spatio - temporal af maps ; ablation guided by identification of focal impulses and rotors improved the overall procedure success . results of catheter ablation in patients with non - paroxysmal af are still not satisfactory . in the meta - analysis by ganesan , rates of single - procedure success for non - paroxysmal af ablation were 50.8% ( 95% ci 34.3% to 67.2% ) at 1 year and 41.6% ( 95% ci 24.7% to 60.8% ) at 3 years . the pooled 12-month success rate after a single procedure was 51.9% ( 95% ci 33.8% to 69.5% ) ; it increased to 77.8% ( 95% ci 68.7% to 84.9% ) when multiple procedures were used ( average number of procedures : 1.67 ) .
atrial fibrillation ( af ) is associated with increases in the risk of mortality , congestive heart failure , and stroke . 
 medical treatment is aimed at preventing thrombo - embolic complications and reducing symptoms and consequences related to the arrhythmia . in the first section of this review , we discuss the principles of mainstream oral anticoagulant therapy and the possible advantages of the new oral anticoagulants . in the second section , 
 we review the catheter ablation approaches to paroxysmal and persistent / long - standing af , their results , and the current application of new catheters .