| Part Ⅰ:The periprocedural use of dabigatran for patients undergoing ablation of atrial tachyarrhythmias:an observational studyBackground:As the first novel oral anticoagulants (NOAC) approved by FDA and CFDA, dabigatran etexilate (DA) works by inhibiting thrombin after intracorporal conversion. The results of RE-LY trial indicated that in patients with non-valvular atrial fibrillation (NVAF), fixed doses of DA (110 mg twice daily or 150mg twice daily) were non-inferior to warfarin with respect to stroke or systemic embolism prevention. In addition, compared with wafarin,110 mg dose was safer with lower incidence of major hemorrhage, and 150 mg dose was more effective in preventing stroke or systemic embolism, yet with a similar risk of major bleeding. Regarding the use of DA during periprocedural period of NVAF catheter ablation, the 2013 consensus recommended withholding DA 12-24 hours before ablation, and resuming the same dose four hours post ablation if active hemorrhage excluded. This recommendation is only suitable for experienced centers, owing to lacking large multicenter randomized controlled trial, diversed results of small observational studies and controversial results of meta-analyses. Since administration of NOACs in patients undergoing catheter ablation of atrial tachyarrhythmias (ATAs) is increasing, its safety and efficacy for such patients should be verified.Objective:This study aims to evaluate the safety and efficacy of periprocedural DA administration in Chinese Han patients undergoing catheter ablation of ATAs by comparing the incidence of thromboembolic events, bleeding events and other side effects with warfarin.Methods:A total of 859 patients with ATAs receiving radiofrequency catheter ablation (RFCA) and periprocedural anticoagulant therapy between September 2013 and April 2015 were screened out from the medical records system of the First Affiliated Hospital of Nanjing Medical University. Among them,165 received DA as periprocedual anticoagulant. Then, accoring to sex, age, types of ATAs and comorbidities,165 patients receiving warfarin were matched as control group. Anticoagulant regimens, bleeding events, thromboembolic events and other side effects (gastrointestinal discomfort, allergies, etc.) were achieved by means of outpatient or telephone follow-up. Statistic analysis was performed using SPSS 20.0.Results:There are no significant difference in baseline characteristic between DA and warfarin group. In the dabigatran group,158(95.8%) patients received 110mg of dabigatran twice daily and other 7 patients received 150mg twice daily; in warfarin group, all patients regularly monitored INR and adjusted warfarin dose to maintain INR between 2.0 and 3.0. Comparing with warfarin group, the total dose of heparin administration through the ablation procedure in DA group was significantly higher (p< 0.001), and baseline activated clotting time (ACT), target ACT for the first time, peak value of ACT were significantly lower (p< 0.001). In the aspect of bleeding complications, major bleeding occurred in 2 patients in both the DA group and warfarin group (p> 0.05), and mild bleeding occurred in 17 patients in the DA group and 16 patients in the warfarin group (p> 0.05), respectively. Neither of the two groups had any thromboembolic complication. The incidence of gastrointestinal adverse complications in the DA group was significantly higher than that in the warfarin group (9.1% vs.0%, p< 0.001), and one of the patients in the DA group switched to warfarin because of intolerable stomachache.Conclusions:Periprocudural adminstration of DA has similar effectiveness and safety comparing with warfarin in Chinese Han patients undergoing catheter ablation of ATAs, while intense monitoring of the ACT during procedure is needed to titrate appropriate heparin dose.Part II:Co-administration of amiodarone and warfarin:drug-drug interaction and dose adjustment of warfarinBackground:Warfarin, which is the first drug used as anticoagulant for patients with atrial fibrillation, is a kind of vitamin K antagonists. It is effective enough in the prevention of stroke and systemic embolism. However, the limitations associated with warfarin administration have posed a significant challenge for its use in clinical practice. These limitations include inter and intra-individual variations in therapeutic levels, drug-drug interaction and frequent internationalized therapeutic ratio (INR) testing. The properties of cytochrome P450-dependent metabolism, and high protein binding are responsible for warfarin to be prone to potentially life-threatening drug-drug interactions and result in a lower time in therapeutic range (TTR) which is associated with a higher incidence of bleeding events. A lot of patients with atrial fibrillation receive at least one kind of class I or III antiarrhythmic drugs to reduce the load of atrial fibrillation and improve the quality of their lives, therefore, amiodarone is often co-administered with warfarin. An interaction always occurs between these two drugs which generally necessitates a dose reduction of warfarin. The first case report of this interaction was published in 1981, which recommended a dose reduction of warfarin when it is co-administered with amiodarone. Many small observational studies reported that amiodarone could enhance the effect of warfarin, and a 6-65% dose reduction of warfarin were recommended. Large sample observational studies indicated that the TTRs of warfarin were significantly lower in the co-amiodarone group compared with non-amiodarone group, which lead to a higher incidence of bleeding complications. So maybe a reasonable dose reduction strategy could help to reduce the risk of bleeding when warfarin and amiodarone were simultaneously prescribed in one patient.Objectives:To investgate the interaction between warfarin and amiodarone in AT As patients by comparing the TTR before and post catheter ablation, and make the dose adjustment plans of warfarin post ablation for these patients.Methods:ATAs patients undergoing RFCA in the First Affiliated Hospital of Nanjing Medical University were enrolled from July 2014 to September 2015. Inclusion criteria were as following:(1) periprocedual administration of warfarin, (2) no amiodarone therapy within six months before ablation procedure, (3)amiodarone co-administration after ablation. INR, dose change of warfarin, dose of amiodarone, bleeding and thrombembolic complications were collected both before and after ablation. TTRs were calculated by the Rosendaal method. The prescription of amiodarone after ablation:(1) venous administration:patients got 0.6-1.8g amidarone through vein after ablation, (2) oral administration:200mg three times daily during the first week, then 200mg twice daily in the second week and then get a maintain dose of 200mg daily from the thrid week after administration of amiodarone. Statistic analysis was performed in SPSS 20.0.Results:A total of 42 patients were included with an average age of 55.24±11.12 years, and 32 (76.2%) of them were male. The mean follow-up time before and post ablation were 38.59 ± 27.96 days and 106.02 ± 45.92 days, respectively. The result indicated that the time ratio of INR>3 of the first month after ablation was significant higher than that pre-ablation (10±14% vs.25±20%, p< 0.05), but no difference was observed between pre-ablation and post-ablation. The peak value of INR post ablation was significant higher than that pre-ablation (2.76±0.48 vs.3.78±0.51, p< 0.05), and the mean time beforing achieving the peak INR was 13.97±7.57 days. There were no significant difference of TTR between pre-ablation and post-ablation. Among the 42 patients,37 needed dose reduction after ablation and the rest kept the same dose as pre-ablation. Dose of warfarin adminstration pre-ablation and post-ablation were 3.70±1.29 mg/d and 2.82±0.99 mg/d (p< 0.05), respectively. Mean dose reduction percentage was 23.3±10%(7%-50%). No thromboembolic and major bleeding events were observed, but six patients sufferred from mild bleeding after ablation.Conclusions:Amiodarone could enhance the efficacy of warfarin, and the ratio of INR>3 was significantly higher during the first month after the co-administration of amiodarone. The peak drug-drug interaction of these two drugs occurred within 14-30 days, thus it is important to monitor INR during the first month post co-administration and reduce the dose of wafarin accordingly. |
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