atrial fibrillation ( af ) is the most common sustained arrhythmia and has a significant impact on morbidity and mortality . applying radiofrequency ( rf ) energy to circumferentially isolate the pulmonary veins ( pvs ) from the left atrium ( la ) , known as pv atrium isolation ( pvai ) , is the most effective treatment for af , with a cure rate between 50% and 90% . atrial fibrillation ablation is one of the most complex interventional electrophysiologic procedures and is thus associated with several important complications . one such complication is thromboembolism . despite the introduction of novel ablation technologies , such as open irrigated catheters , and the widespread use of systemic anticoagulation with heparin , the risk of periprocedural thromboembolism remains notable , reaching approximately 1%2% in large series . over the past 5 years , noacs , such as rivaroxaban and dabigatran etexilate , have been approved for long - term oral anticoagulation , all of which have demonstrated safety , efficacy , and suitability for anticoagulation in patients with nonvalvular af . non - vitamin k antagonist oral anticoagulants offer several advantages over traditional anticoagulants : they have short half - lives , are easy to administer , have few interactions , and do not require laboratory monitoring . all intraprocedural anticoagulation strategies use systemic unfractionated heparin guided by activated clotting time ( act ) , with a recommended target within 300350 seconds . drug manufacturers provide recommended dosages for noacs , which are determined primarily by renal function . dosages of noacs can be divided into three categories : adjusted low dosage is a dose reduced according to renal faction , as stipulated by the manufacturer . underdosage can be defined as a dose lower than a standard dose in patients without renal disturbance . few studies have reported on the efficacy of underdosing dabigatran for anticoagulation in af ablation . the recommended dosage of rivaroxaban is reduced for asian patients because of relatively low body weights when compared to western populations . the efficacy of rivaroxaban for deep vein thrombosis has been validated over a wide range of dosages , from 20 to 40 mg / d . such results indicate that underdosing noacs is not necessarily associated with a loss of efficacy . therefore , this study sought to identify the safety and efficacy of underdosing noacs for perioperative anticoagulation in patients undergoing af ablation . a single - center , retrospective study was conducted at the okayama heart clinic , okayama , japan , and included patients who underwent af ablation between april 2011 and december 2014 . data from 120 days of anticoagulation therapy ( from 30 days before to 90 days after ) were analyzed . examination and analysis procedures complied with the rules of the declaration of helsinki , and the study was approved by the institutional ethics committee for human research of okayama heart clinic . written informed consent for the use of data without personally identifiable information a total of 1020 patients ( age , 64  10 years ; 736 men , 284 women ; 658 with paroxysmal af , 362 with nonparoxysmal af ) were included . non - vitamin k antagonist oral anticoagulant selection and dosages were at the discretion of the treating physician . administered dosages were defined as follows : adjusted low dosage was a reduction in dose according to renal function , as stipulated by the drug manufacturer ; standard dosage was the manufacturer recommended dose for patients with creatinine clearance > 50 ml / min ; and underdosage was defined as a dosage lower than the manufacturer recommended dose for patients with creatinine clearance > 50 ml / min ( table 1 ) . standard dosage , underdosage , and adjusted low dosage for each non - vitamin k antagonist oral anticoagulant first , patients were divided into three groups according to dosage ( adjusted low dosage , underdosage , or standard dosage ) . subsequently , patients were divided into two subgroups according to the noac type ( rivaroxaban or dabigatran etexilate ) . rivaroxaban was administered once daily , in the morning , and was initiated at least 30 days before af ablation . dabigatran etexilate was administered twice daily , in the morning and evening , and was initiated at least 30 days before af ablation . non - vitamin k antagonist oral anticoagulants were not administered before the ablation procedure on the day of af ablation . in all patients , a single dose of each noac was resumed three hours after af ablation , without any additional dose on the day of the af ablation procedure . schematic presentation of the anticoagulation medication regimens for the two non - vitamin k antagonist oral anticoagulants ( noacs ) . after completing af ablation , heparin was discontinued and protamine sulfate was administered intravenously at a dose of 20 mg or 30 mg , depending on whether the act was 300350 or > 350 seconds , respectively . when bleeding at the puncture site did not stop after the initial administration of protamine sulfate , additional doses ( 1030 mg , dependent on bleeding status ) were administered at 4 minutes intervals until the bleeding stopped . all patients underwent transesophageal echocardiography immediately before ablation as a means of examining the la and la appendage ( laa ) for thrombi . when af ablation was performed in the afternoon , heparin ( 5000 u ) was administered subcutaneously the same morning . before transseptal catheterization , an intravenous heparin bolus ( 100130 u / kg ) after transseptal catheterization , heparinized saline was infused continuously via a peripheral vein ( 400 u / h ) to maintain the act within 300350 seconds to avoid thrombus formation . two standard electrophysiology catheters were positioned : a 4-f catheter ( japan lifeline co , ltd , tokyo , japan ) in the his bundle region via the femoral vein and a 6-f catheter in the coronary sinus via the right intrajugular vein . paul , mn ) were advanced to the la using the brockenbrough technique , with all sheaths over 1 puncture site . three catheters were positioned in the la : two decapolar ring catheters ( japan lifeline co , ltd ) and one ablation catheter . the ablation strategy was the same in all groups , and pvai was performed in all patients . electrophysiological mapping was performed using a 3.5-mm - tip ablation catheter ( coolflex ; st . each pv ostium was identified using an electroanatomic integration mapping system ( ensite navx system ; st . after la reconstruction , each pv ostium was identified by selective venography and tagged on the electroanatomic map . two decapolar ring catheters were placed within the ipsilateral superior and inferior pvs or within the superior and inferior branches of a common pv during radiofrequency delivery . irrigated radiofrequency energy was delivered with a target temperature of 43c , a maximal power limit of 35 w ( 2030 w for posterior wall ablation and 3035 w for anterior wall ablation ) , and an infusion rate of 813 ml / min via the irrigated ablation catheter . radiofrequency energy was applied for 30 seconds , until the maximal local electrogram amplitude decreased by 70% . irrigated radiofrequency ablation was performed in the posterior and anterior walls at 510 mm and 5 mm , respectively , from the angiographically or electrophysiologically defined pv ostia . the temperature of the esophagus during ablation was continuously monitored by a catheter with a temperature sensor ( sensitherm ; st . the end point of pvai was defined as : ( 1 ) elimination of pv potentials , as recorded by 2 ring catheters within the ipsilateral pvs , and lack of la capture during intra - pv , isthmus , and pv atrial pacing at least 30 minutes after isolation ; and ( 2 ) no recurrence of pv spikes within any of the pvs after intravenous administration of 2040 mg of adenosine triphosphate during sinus rhythm or coronary sinus pacing . in patients with paroxysmal af , only pvai was performed . in patients with persistent and long - standing persistent af , after pvai , a left atrial roof line was created , and subsequent ablation of fractionated atrial electrograms in the right atrium and la and in the coronary sinus was performed . if the af did not terminate after ablation procedures , direct current cardioversion was performed to restore normal sinus rhythm . after the ablation procedure , anticoagulation therapy was continued for at least three months in all groups . patients were followed - up at our center every month for at least 90 days . all previously ineffective antiarrhythmic drugs were withdrawn immediately after ablation . at follow - up , a surface electrocardiogram ( ecg ) was recorded , and transthoracic echocardiography was performed at our center . all patients were given a telemetry electrocardiogram recorder ( omron co , ltd , kyoto , japan ) to document symptomatic arrhythmias or to transfer electrocardiogram data once per week if they remained asymptomatic for 6 months . cerebrovascular accidents and transient ischemic attacks were considered as thromboembolic complications once intracranial hemorrhage had been ruled out . cardiac tamponade , retroperitoneal bleeding , and groin hematoma requiring blood transfusion were defined as major bleeding episodes . cardiac tamponade was defined by characteristic clinical features and the presence of a considerable pericardial effusion requiring drainage . pericardial effusion , reduced hemoglobin without blood transfusion , and hematuria were defined as minor complications . a pericardial effusion was defined as an effusion identified in the pericardial space by routine follow - up echocardiography without hemodynamic disturbance ( nontamponade ) . data were expressed as mean  sd . when comparing two groups , student t - tests and  tests were used for continuous and categorical variables , respectively . for multiple comparisons of continuous variables , including act levels among the three dosage groups , we used a one - way analysis of variance ( anova ) or kruskal  wallis test , and the scheffe f test or mann  whitney u test with bonferroni correction as a post hoc test to compare two groups in multiple groups , when appropriate . the  test with multiple tables and two - tailed test for categorical variables were used to evaluate differences among the three dosage groups . a single - center , retrospective study was conducted at the okayama heart clinic , okayama , japan , and included patients who underwent af ablation between april 2011 and december 2014 . data from 120 days of anticoagulation therapy ( from 30 days before to 90 days after ) were analyzed . examination and analysis procedures complied with the rules of the declaration of helsinki , and the study was approved by the institutional ethics committee for human research of okayama heart clinic . written informed consent for the use of data without personally identifiable information a total of 1020 patients ( age , 64  10 years ; 736 men , 284 women ; 658 with paroxysmal af , 362 with nonparoxysmal af ) were included . non - vitamin k antagonist oral anticoagulant selection and dosages were at the discretion of the treating physician . administered dosages were defined as follows : adjusted low dosage was a reduction in dose according to renal function , as stipulated by the drug manufacturer ; standard dosage was the manufacturer recommended dose for patients with creatinine clearance > 50 ml / min ; and underdosage was defined as a dosage lower than the manufacturer recommended dose for patients with creatinine clearance > 50 ml / min ( table 1 ) . standard dosage , underdosage , and adjusted low dosage for each non - vitamin k antagonist oral anticoagulant first , patients were divided into three groups according to dosage ( adjusted low dosage , underdosage , or standard dosage ) . subsequently , patients were divided into two subgroups according to the noac type ( rivaroxaban or dabigatran etexilate ) . rivaroxaban was administered once daily , in the morning , and was initiated at least 30 days before af ablation . dabigatran etexilate was administered twice daily , in the morning and evening , and was initiated at least 30 days before af ablation . non - vitamin k antagonist oral anticoagulants were not administered before the ablation procedure on the day of af ablation . in all patients , a single dose of each noac was resumed three hours after af ablation , without any additional dose on the day of the af ablation procedure . schematic presentation of the anticoagulation medication regimens for the two non - vitamin k antagonist oral anticoagulants ( noacs ) . after completing af ablation , heparin was discontinued and protamine sulfate was administered intravenously at a dose of 20 mg or 30 mg , depending on whether the act was 300350 or > 350 seconds , respectively . when bleeding at the puncture site did not stop after the initial administration of protamine sulfate , additional doses ( 1030 mg , dependent on bleeding status ) were administered at 4 minutes intervals until the bleeding stopped . all patients underwent transesophageal echocardiography immediately before ablation as a means of examining the la and la appendage ( laa ) for thrombi . when af ablation was performed in the afternoon , heparin ( 5000 u ) was administered subcutaneously the same morning . before transseptal catheterization , an intravenous heparin bolus ( 100130 u / kg ) after transseptal catheterization , heparinized saline was infused continuously via a peripheral vein ( 400 u / h ) to maintain the act within 300350 seconds to avoid thrombus formation . two standard electrophysiology catheters were positioned : a 4-f catheter ( japan lifeline co , ltd , tokyo , japan ) in the his bundle region via the femoral vein and a 6-f catheter in the coronary sinus via the right intrajugular vein . paul , mn ) were advanced to the la using the brockenbrough technique , with all sheaths over 1 puncture site . three catheters were positioned in the la : two decapolar ring catheters ( japan lifeline co , ltd ) and one ablation catheter . the ablation strategy was the same in all groups , and pvai was performed in all patients . electrophysiological mapping was performed using a 3.5-mm - tip ablation catheter ( coolflex ; st . each pv ostium was identified using an electroanatomic integration mapping system ( ensite navx system ; st . after la reconstruction , each pv ostium was identified by selective venography and tagged on the electroanatomic map . two decapolar ring catheters were placed within the ipsilateral superior and inferior pvs or within the superior and inferior branches of a common pv during radiofrequency delivery . irrigated radiofrequency energy was delivered with a target temperature of 43c , a maximal power limit of 35 w ( 2030 w for posterior wall ablation and 3035 w for anterior wall ablation ) , and an infusion rate of 813 ml / min via the irrigated ablation catheter . radiofrequency energy was applied for 30 seconds , until the maximal local electrogram amplitude decreased by 70% . irrigated radiofrequency ablation was performed in the posterior and anterior walls at 510 mm and 5 mm , respectively , from the angiographically or electrophysiologically defined pv ostia . the temperature of the esophagus during ablation was continuously monitored by a catheter with a temperature sensor ( sensitherm ; st . the end point of pvai was defined as : ( 1 ) elimination of pv potentials , as recorded by 2 ring catheters within the ipsilateral pvs , and lack of la capture during intra - pv , isthmus , and pv atrial pacing at least 30 minutes after isolation ; and ( 2 ) no recurrence of pv spikes within any of the pvs after intravenous administration of 2040 mg of adenosine triphosphate during sinus rhythm or coronary sinus pacing . in patients with paroxysmal af , only pvai was performed . in patients with persistent and long - standing persistent af , after pvai , a left atrial roof line was created , and subsequent ablation of fractionated atrial electrograms in the right atrium and la and in the coronary sinus was performed . if the af did not terminate after ablation procedures , direct current cardioversion was performed to restore normal sinus rhythm . after the ablation procedure , anticoagulation therapy was continued for at least three months in all groups . patients were followed - up at our center every month for at least 90 days . all previously ineffective antiarrhythmic drugs were withdrawn immediately after ablation . at follow - up , a surface electrocardiogram ( ecg ) was recorded , and transthoracic echocardiography was performed at our center . all patients were given a telemetry electrocardiogram recorder ( omron co , ltd , kyoto , japan ) to document symptomatic arrhythmias or to transfer electrocardiogram data once per week if they remained asymptomatic for 6 months . cerebrovascular accidents and transient ischemic attacks were considered as thromboembolic complications once intracranial hemorrhage had been ruled out . cardiac tamponade , retroperitoneal bleeding , and groin hematoma requiring blood transfusion were defined as major bleeding episodes . cardiac tamponade was defined by characteristic clinical features and the presence of a considerable pericardial effusion requiring drainage . pericardial effusion , reduced hemoglobin without blood transfusion , and hematuria were defined as minor complications . a pericardial effusion was defined as an effusion identified in the pericardial space by routine follow - up echocardiography without hemodynamic disturbance ( nontamponade ) . data were expressed as mean  sd . when comparing two groups , student t - tests and  tests were used for continuous and categorical variables , respectively . for multiple comparisons of continuous variables , including act levels among the three dosage groups , we used a one - way analysis of variance ( anova ) or kruskal  wallis test , and the scheffe f test or mann  whitney u test with bonferroni correction as a post hoc test to compare two groups in multiple groups , when appropriate . the  test with multiple tables and two - tailed test for categorical variables were used to evaluate differences among the three dosage groups . the average age of patients in the underdosage group was higher than that in the standard - dosage group and lower than that in the adjusted low - dosage group . the underdosage group also had a higher percentage of female patients than the standard - dosage group . body weight and body mass index in the underdosage group were lower than those in the standard - dosage group and higher than those in the adjusted low - dosage group . creatinine clearance in the underdosage group was lower than that in the standard - dosage group and higher than that in the adjusted low - dosage group . sex , age , body weight , body mass index , and creatinine clearance exhibited significant correlations in all patients and in each noac group , with a few exceptions ( table 4 ) . clinical and arrhythmia conditions , activated clotting time , heparin and protamine dosages , and procedural time according to dosage clinical and arrhythmia conditions , activated clotting time , heparin and protamine dosages , and procedural time according to non - vitamin k antagonist oral anticoagulant administered and dosage correlations among patient characteristics chads2 and cha2ds2-vasc scores in the underdosage group were higher than those in the standard - dosage group and lower than those in the adjusted low - dosage group . when patient characteristics were compared among the three dosage categories for both rivaroxaban and dabigatran etexilate , identical results were obtained in each noac subcategory . procedural times did not differ among patients who received adjusted low- , under- , and standard dosages of noacs or among dosage subgroups for each noac ( tables 2 and 3 ) . all patients reached the endpoint of pvai , and the initial success rate was thus the same in all groups and subgroups . although act at baseline and at the completion of ablation in patients from the underdosage group was significantly longer than those in the standard - dosage group , differences were not clinically meaningful ( table 2 ) . however , no differences in act were observed among all dosage groups at 15 minutes after the start of ablation . when analyses were performed separately for each noac subgroup , no dosage - related differences in acts before or after ablation could be identified . the total dosage of heparin per kilogram of body weight required during the procedure to maintain an act of 300350 seconds did not differ among patients who received adjusted low- , under- , and standard - dosage noacs . similarly , in each noac subgroup , no significant differences in the total dosage of heparin per kilogram of body weight required during the procedure were observed among dosage groups . the dosage of protamine required for hemostasis after termination of af ablation also did not differ among patients receiving adjusted low- , under- , and standard - dosage noacs , nor were there any differences when the analysis was performed for each noac separately ( table 3 ) . no patients in any group exhibited thromboembolic or bleeding complications in the 30 days before ablation . transesophageal echocardiography performed immediately before ablation did not identify la or laa thrombosis in any patient . during the procedural and periprocedural periods , only one patient ( 1/1020 , 0.09% ) consequently , there were no significant differences in thromboembolic complications among the adjusted low- , under- , and standard - dosage patients , either overall ( table 5 ) , or when analyzed separately for each noac ( table 6 ) . no significant differences were noted in the incidence of major and minor bleeding among patients with adjusted low- , under- , and standard - dosage noacs , either overall or in each noac subgroup analyzed separately . comparison of complications among patients with adjusted low- , under- , and standard - dosage non - vitamin k antagonist oral anticoagulants comparison of complications among patients with adjusted low- , under- , and standard - dosage non - vitamin k antagonist oral anticoagulants during the 90-day follow - up period after af ablation , neither thromboembolic nor bleeding complications were observed . as a whole , safety outcomes did not differ among adjusted low- , under- , and standard - dosage groups ( table 5 ) , nor were there any differences when the analysis was performed for each noac separately ( table 6 ) . the average age of patients in the underdosage group was higher than that in the standard - dosage group and lower than that in the adjusted low - dosage group . the underdosage group also had a higher percentage of female patients than the standard - dosage group . body weight and body mass index in the underdosage group were lower than those in the standard - dosage group and higher than those in the adjusted low - dosage group . creatinine clearance in the underdosage group was lower than that in the standard - dosage group and higher than that in the adjusted low - dosage group . sex , age , body weight , body mass index , and creatinine clearance exhibited significant correlations in all patients and in each noac group , with a few exceptions ( table 4 ) . clinical and arrhythmia conditions , activated clotting time , heparin and protamine dosages , and procedural time according to dosage clinical and arrhythmia conditions , activated clotting time , heparin and protamine dosages , and procedural time according to non - vitamin k antagonist oral anticoagulant administered and dosage correlations among patient characteristics chads2 and cha2ds2-vasc scores in the underdosage group were higher than those in the standard - dosage group and lower than those in the adjusted low - dosage group . when patient characteristics were compared among the three dosage categories for both rivaroxaban and dabigatran etexilate , identical results were obtained in each noac subcategory . procedural times did not differ among patients who received adjusted low- , under- , and standard dosages of noacs or among dosage subgroups for each noac ( tables 2 and 3 ) . all patients reached the endpoint of pvai , and the initial success rate was thus the same in all groups and subgroups . although act at baseline and at the completion of ablation in patients from the underdosage group was significantly longer than those in the standard - dosage group , differences were not clinically meaningful ( table 2 ) . however , no differences in act were observed among all dosage groups at 15 minutes after the start of ablation . when analyses were performed separately for each noac subgroup , no dosage - related differences in acts before or after ablation could be identified . the total dosage of heparin per kilogram of body weight required during the procedure to maintain an act of 300350 seconds did not differ among patients who received adjusted low- , under- , and standard - dosage noacs . similarly , in each noac subgroup , no significant differences in the total dosage of heparin per kilogram of body weight required during the procedure were observed among dosage groups . the dosage of protamine required for hemostasis after termination of af ablation also did not differ among patients receiving adjusted low- , under- , and standard - dosage noacs , nor were there any differences when the analysis was performed for each noac separately ( table 3 ) . no patients in any group exhibited thromboembolic or bleeding complications in the 30 days before ablation . transesophageal echocardiography performed immediately before ablation did not identify la or laa thrombosis in any patient . during the procedural and periprocedural periods , only one patient ( 1/1020 , 0.09% ) experienced a transient ischemic attack , but recovered promptly ( table 5 ) . consequently , there were no significant differences in thromboembolic complications among the adjusted low- , under- , and standard - dosage patients , either overall ( table 5 ) , or when analyzed separately for each noac ( table 6 ) . no significant differences were noted in the incidence of major and minor bleeding among patients with adjusted low- , under- , and standard - dosage noacs , either overall or in each noac subgroup analyzed separately . comparison of complications among patients with adjusted low- , under- , and standard - dosage non - vitamin k antagonist oral anticoagulants comparison of complications among patients with adjusted low- , under- , and standard - dosage non - vitamin k antagonist oral anticoagulants during the 90-day follow - up period after af ablation , neither thromboembolic nor bleeding complications were observed . as a whole , safety outcomes did not differ among adjusted low- , under- , and standard - dosage groups ( table 5 ) , nor were there any differences when the analysis was performed for each noac separately ( table 6 ) . the present study demonstrated that underdosing the noacs rivaroxaban and dabigatran etexilate , which involves administering a dosage lower than that recommended by the drug manufacturer , provided safe and effective anticoagulation for patients undergoing catheter ablation for af . dosages were selected according to the discretion of the treating cardiologist , with consideration of age , sex , body weight and body mass index , and creatinine clearance . underdosage was considered to be clinically appropriate in a considerable number of patients , indicating that efficacy and safety exists over a wider range of doses than the drug manufacturer recommends . catheter ablation of af in this study was performed in essentially the same manner as improved methods described recently . procedural times in all groups analyzed were comparable to or shorter than those in recent reports . heparin was administered to maintain an act in the range 300350 seconds , in accordance with generally accepted practice . all patients reached the endpoint of successful af ablation , and the overall complication rate was comparable to or less than that described in recent reports . the present procedural parameters and clinical outcomes indicate that these methods for af ablation were satisfactory . the present study identified no differences in thromboembolic and bleeding complications between underdosage and standard - dosage patients . further , no differences were observed between rivaroxaban and dabigatran etexilate . about rivaroxaban , research has noted that doses of 20 , 30 , and 40 mg / d appear to be equivalent in safety and efficacy for the treatment of deep venous thrombosis . in comparison , rivaroxaban dosages used in this study were lower , at 10 mg / d in the underdosage group . this would account for the considerably low incidence of bleeding complications ( 0.8% ) observed in the present study . the standard dosage of rivaroxaban in asian patients is less than that of western populations , typically between 20 and 15 mg / d , given differences in population pharmacokinetics and pharmacodynamics . the efficacy and safety of a 15 mg / d dosage of rivaroxaban has been reported in the treatment of nonvalvular af patients . however , underdosing rivaroxaban in patients undergoing af ablation is poorly researched , and the present study can not be compared with reported studies . about dabigatran etexilate , one study in which comparisons were made with acenocoumarol noted that underdosages of 110 mg twice daily were safe and efficacious for perioperative anticoagulation in patients undergoing af ablation . however , the study in question included few patients who were young compared with the population observed here and had longer procedural times and higher complication rates , thereby making comparisons with present results difficult . additionally , a randomized study has examined the comparative safety and efficacy of underdosing dabigatran against warfarin in patients undergoing af ablation . similarly , however , the study included few of patients ( n = 45 in each group ) and did not perform comparisons with standard doses of dabigatran etexilate . despite such insufficiencies , previously reported results are largely consistent with those observed in this study . in clinical flowcharts for dabigatran etexilate in af , a 110 mg dose is recommended in patients of advanced age , even with preserved creatinine clearance or low thromboembolic risk and high bleeding risk . considered together , the present study suggests that underdosing noacs , such as rivaroxaban and dabigatran etexilate , is safe and efficacious in the perioperative anticoagulation of patients undergoing af ablation . overall , the rate of bleeding complications was less than or comparable to that reported in other studies . bleeding complications are assumed to be related to a hemorrhagic tendency or to technical , procedural , and anatomical factors . given that the act was controlled and there were no differences in the incidence of bleeding complications between under- and standard - dosage groups , we may conclude that neither adjusted low- , under- , nor standard - dosage noacs play a major role in bleeding complications . furthermore , the accumulation of experience and improved methods , including ablation devices , has reduced the incidence of bleeding complications . indeed , the incidence of cardiac tamponade in the present study was 0.5% , lower than that reported in previous studies . a thromboembolic complication was observed in just one patient who experienced a transient ischemic attack . this suggests that under- and standard - dosage noacs are effective in the prevention of thromboembolic complications . when selecting noac dosages , underdosing was associated with female sex , advanced age , lower body weight , and poorer renal function in all patients and in both noac subgroups . further , significant correlations among body weight , age , sex , and renal function were observed ( table 4 ) . risk scores for stroke ( chads2 , cha2ds2-vasc ) were higher in the underdosage group than those in the standard - dosage group . in these risk score systems , the underdosage group exhibited a higher incidence of both female sex and advanced age that would , at least partly , account for a higher risk score in the underdosage group than the standard - dosage group . in each noac subgroup , the act immediately before the af ablation procedure was slightly but significantly elevated ; however , no significant differences were observed among patients receiving adjusted low- , under- , and standard dosages of noacs . further , the quantity of heparin per kilogram of body weight required to maintain an act in the range of 300350 seconds did not differ between patients among under- , standard- , and adjusted low - dosages , nor were any differences observed in each noac subgroup considered separately . in addition , the dose of protamine needed for homeostasis also showed no differences among patients receiving under- , standard- , and adjusted low - dosage noacs , overall or for each noac individually . such results suggest that blood coagulation activity was suppressed equally and significantly by all noac dosages used in this study and account for observations about equivalent safety and efficacy . an indirect comparison has previously suggested that significant differences exist in safety and efficacy among noacs . however , the present study did not reveal any such differences : underdosing two different noacs had no effect on their safety and efficacy in the context of anticoagulation . there have been no reports of thromboembolic or bleeding episodes in patients receiving underdosage noacs compared to those with standard - dosage noacs , and the present results suggest that underdosage of both rivaroxaban and dabigatran etexilate , at physician discretion , is safe and effective in the prevention of thromboembolism in af patients . second , the study was conducted in a retrospective manner and therefore lacks the power of a prospective randomized study . although it appears that an increase in the number of patients would most likely not produce significant changes in results , multicenter studies with a greater number of patients are required to confirm the results observed in this study . underdosing noacs , which involves administering a dosage lower than that recommended by the drug manufacturer ( standard dose ) , is safe and efficacious for the perioperative anticoagulation of patients undergoing af ablation , provided adequate consideration is given to patient condition , age , sex , body weight , body mass index , and renal function . the results of this study indicate that the therapeutic range of noacs is wider than the manufacturer recommended dosage .
background : some patients with atrial fibrillation ( af ) received underdoses of non - vitamin k antagonist oral anticoagulants ( noacs ) in the real world . underdosing is defined as administration of a dose lower than the manufacturer recommended dose.objectives:to identify the efficacy and safety of underdosing noacs as perioperative anticoagulation for atrial fibrillation ablation.methods:we retrospectively analyzed patients who received rivaroxaban or dabigatran etexilate according to dosage : adjusted low dosage ( reduced by disturbed renal function ; n = 30 ) , underdosage ( n = 307 ) , or standard dosage ( n = 683 ) . 
 non - vitamin k antagonist oral anticoagulants and dosing decisions were at the discretion of treating cardiologists.results:patients who received underdosed noacs were older , more often female , and had lower body weight and lower renal function than those who received standard dosages . 
 activated clotting time at baseline in patients who received adjusted low dosage or underdosages was slightly longer than that in patients receiving standard dosages ( 156  23 , 151  224 , and 147  24 seconds , respectively ) . 
 meaningful differences were not observed in other coagulation parameters . 
 adjusted low- , under- , and standard - dosing regimens did not differ in perioperative thromboembolic complications ( 0/30 , 0.0% ; 1/307 , 0.3% ; and 0/683 , 0% , respectively ) or major ( 0/30 , 0.0% ; 2/307 , 0.6% ; 3/683 , 0.4% ) and minor ( 1/30 , 3.3% ; 13/307 , 4.2% ; 25/683 , 3.6% ) bleeding episodes . when comparisons were performed for each noac , similar results were observed.conclusions:with consideration of patient condition , age , sex , body weight , body mass index , and renal function , underdosing noacs was effective and safe as a perioperative anticoagulation therapy for atrial fibrillation ablation . 
 the therapeutic range of noacs is potentially wider than manufacturer recommendations .