Effectiveness and Safety of Direct Oral Anticoagulants in Thai Patients with Atrial Fibrillation: A Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation (AF). However, studies into their effectiveness and safety in the Thai population have so far been limited. OBJECTIVES: To study the effectiveness and safety of warfarin and DOACs among Thai AF patients. METHODS: A retrospective cohort study was conducted on AF patients at Ramathibodi Hospital from 2013 to 2018. All patients were followed for at least 1 year. Relevant clinical information was collected and compared between AF patient groups receiving warfarin, dabigatran, rivaroxaban, and apixaban. The primary outcome was a composite of major bleeding, ischemic stroke, and systemic thromboembolism. The secondary outcomes were all-cause mortality and disease-specific mortality caused by major bleeding, ischemic stroke, and systemic thromboembolism. RESULTS: A total of 1680 AF patients were enrolled in the study (warfarin 1193, apixaban 140, dabigatran 193, rivaroxaban 114). The estimated incidence of composite outcome was 16% [95% CI, 14-18%] and 12.4% [95% CI, 9.4-15.3%] in the warfarin and DOAC group, respectively, given a number needed to treat of 28 [95% CI, 3-52]. Compared with warfarin, DOACs were associated with both lower rate of all-cause mortality (4.9% [22/447] vs 8% [98/1193]) and lower disease-specific mortality (0.4% [2/447] and 1% [12/1193]). CONCLUSIONS: This study suggests DOACs were associated with a lower risk of major bleeding, ischemic stroke, and systemic thromboembolism compared to warfarin in Thai patients with AF. Patients receiving DOAC also had a lower rate of all-cause mortality and disease-specific mortality.

Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand.

BACKGROUND: Mutations in SCN5A are rarely found in Thai patients with Brugada syndrome (BrS). Recent evidence suggested that common genetic variations may underlie BrS in a complex inheritance model. OBJECTIVE: The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand. METHODS: We conducted a genome-wide association study (GWAS) to explore the association of common variants in 154 Thai BrS cases and 432 controls. We sequenced SCN5A in 131 cases and 205 controls. Variants were classified according to current guidelines, and case-control association testing was performed for rare and low-frequency variants. RESULTS: Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 × 10-10). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 × 10-10). The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 × 10-9). Rare (minor allele frequency [MAF] <0.0001) coding variants in SCN5A were found in 8 of the 131 cases (6.1% in cases vs 2.0% in controls; P = .046; OR 3.3; 95% confident interval [CI] 1.0-11.1), but an enrichment of low-frequency (MAF<0.001 and >0.0001) variants also was observed in cases, with 1 variant (SCN5A: p.Arg965Cys) detected in 4.6% of Thai BrS patients vs 0.5% in controls (P = 0.015; OR 9.8; 95% CI 1.2-82.3). CONCLUSION: The genetic basis of BrS in Thailand includes a wide spectrum of variant frequencies and effect sizes. As previously shown in European and Japanese populations, common variants near SCN5A and HEY2 are associated with BrS in the Thai population, confirming the transethnic transferability of these 2 major BrS loci.

Mapping and Ablation of Ventricular Fibrillation Associated With Early Repolarization Syndrome.

BACKGROUND: We conducted a multicenter study to evaluate mapping and ablation of ventricular fibrillation (VF) substrates or VF triggers in early repolarization syndromes (ERS) or J-wave syndrome (JWS). METHODS: We studied 52 patients with ERS (4 women; median age, 35 years) with recurrent VF episodes. Body surface electrocardiographic imaging and endocardial and epicardial electroanatomical mapping of both ventricles were performed during sinus rhythm and VF for localization of triggers, substrates, and drivers. Ablations were performed on VF substrates, defined as areas that had late depolarization abnormalities characterized by low-voltage fractionated late potentials, and VF triggers. RESULTS: Fifty-one of the 52 patients had detailed mapping that revealed 2 phenotypes: group 1 had late depolarization abnormalities predominantly at the right ventricular (RV) epicardium (n=40), and group 2 had no depolarization abnormalities (n=11). Group 1 can be subcategorized into 2 groups: Group 1A included 33 patients with ERS with Brugada electrocardiographic pattern, and group 1B included 7 patients with ERS without Brugada electrocardiographic pattern. Late depolarization areas colocalize with VF driver areas. The anterior RV outflow tract/RV epicardium and the RV inferior epicardium are the major substrate sites for group 1. The Purkinje network is the leading underlying VF trigger in group 2 that had no substrates. Ablations were performed in 43 patients: 31 and 5 group 1 patients had only VF substrate ablation and VF substrates plus VF trigger, respectively (mean, 1.4±0.6 sessions); 6 group 2 patients and 1 patient without group classification had only Purkinje VF trigger ablation (mean, 1.2±0.4 sessions). Ablations were successful in reducing VF recurrences (P<0.0001). After follow-up of 31±26 months, 39 (91%) had no VF recurrences. CONCLUSIONS: There are 2 phenotypes of ERS/J-wave syndrome: one with late depolarization abnormality as the underlying mechanism of high-amplitude J-wave elevation that predominantly resides in the RV outflow tract and RV inferolateral epicardium, serving as an excellent target for ablation, and the other with pure ERS devoid of VF substrates but with VF triggers that are associated with Purkinje sites. Ablation is effective in treating symptomatic patients with ERS/J-wave syndrome with frequent VF episodes.

Efficacy of Blood Pressure reduction of Losartan in selected Thai populations using Home Blood Pressure Monitoring and Office Blood Pressure measurements.

BACKGROUND: Angiotensin Receptor Blockades (ARB) is becoming a first line drug for essential Hypertension for many types of patient. Losartan is the prototype of ARB due to its vast clinical trials. Home Blood pressure monitoring can provide accurate evaluation of certain drug effect on blood pressure with small number of patient samples. Local production of medicine has made the Medicine readily available and could bring about clinical improvement. Our hypothesis was that Thai population with essential hypertension responded quite well to Losartan and Generic Losartan was not inferior to Original- Losartan. OBJECTIVE: To evaluate the effectiveness and safety in BP reduction by Losartan in certain Thai population and to compare these parameters between Generic Losartan and Original-Losartan using both office and HBPM method. METHOD: After a two-week run-in period when they would learn to use HBPM device and their blood pressure were still recorded to be higher than 140/90 by office BP or 135/85 by HBPM with or without previous medical regimen, 24 patients were randomized to receive either Generic Losartan or Original-Losartan for 6 weeks. Then they would cross over to receive the alternative and were followed again at 6 weeks. HBPM was performed in the morning and in the evening for 5 days, at baseline, and after 6 & 12 weeks. Office BP measurements were obtained at baseline and after 6 & 12 weeks. RESULT: One patient in each group dropped out from the study. 22 patients with average age of 54 and averaged office BP 154/88 completed the 12 weeks study. By office BP, SBP was reduced by 27±14.2 at week 6 and 28±15.1 mmHg at week 12. By HBPM, SBP dropped by 17±10.8 at week 6 and by 18±9. at week12. At the end of 12 weeks 68% (15/22) of patients had Office BP <140/90 and 64% (14/22) of patients had HBPM <135/85. There was no significant difference of BP reduction at week 6 between Original-xLosartan and Generic Losartan group. After crossover the BP reduction was maintained in both groups. The percentage of patient whose Office BP <140/90 or HBPM <135/85 were not different among the two Losartan groups. There was no serious adverse side effect. CONCLUSION: Using both office BP and HBPM this group of Thai patient with essential hypertension responded well to Losartan and Generic Losartan.

Benefits and risks of catheter ablation in elderly patients with atrial fibrillation.

BACKGROUND: The benefits of catheter ablation for elderly patients with atrial fibrillation (AF) with respect to mortality and stroke reductions remain unclear. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy, including long-term outcomes, of catheter ablation for maintaining normal sinus rhythm (NSR) in elderly patients with AF. METHODS: We evaluated 587 elderly patients (age ≥75 years) with AF. Of the 324 who were eligible for ablation, 261 (group 1) underwent ablation guided by complex fractionated atrial electrogram. The remaining 63 patients (group 2) either declined or were not suitable for ablation. The end-points were NSR, stroke, death, and major bleeding. RESULTS: Two hundred sixteen patients (83%) remained in NSR compared to only 14 group 2 patients (22%; mean follow-up 3 ± 2.5 years, P <.001). The 1- and 5-year survival rates for group 1 with NSR, group 1 with AF, and group 2 patients were 98% and 87%, 86% and 52%, and 97% and 42%, respectively (P <.0001). NSR was an independent favorable parameter for survival (hazard ratio [HR] 0.36; 95% CI, 0.02-0.63, p = 0.0005), whereas older age (HR 1.09, 95% CI 1.01-1.16, P = .02) and depressed ejection fraction <40% (HR 2.38, 95% CI 1.28-4.4, P = .006) were unfavorable. Warfarin therapy was discontinued in 169 of the 216 group 1 patients (78%) who maintained NSR and had only 3% 5-year stroke/bleeding rates compared to 16% in group 2 (P <.001). CONCLUSION: Elderly patients with AF benefit from AF ablation, which is safe and effective in maintaining sinus rhythm and is associated with lower mortality and stroke risks.

Dabigatran versus warfarin anticoagulation before and after catheter ablation for the treatment of atrial fibrillation.

BACKGROUND: Systemic thromboembolism and bleeding remain the two most common and serious complications of catheter ablation of atrial fibrillation. A variety of periprocedure anticoagulation strategies have been proposed to mitigate these risks. Although operators are now routinely administering dabigatran for anticoagulation in this setting, its relative safety and effectiveness compared to warfarin are unknown. METHODS AND RESULTS: A total of 202 patients received dabigatran as part of their periprocedural anticoagulation regimen at the time of initial or redo catheter ablation for symptomatic atrial fibrillation. A comparison group of 202 patients treated with warfarin was randomly selected from patients undergoing atrial fibrillation (AF) ablation during the same time period. AF types were paroxysmal in 223 patients, persistent in 158 patients, and longstanding persistent in 13 patients. Mean age was 60.0 ± 10.5 years, 55 % had a history of hypertension, and mean CHADS-VASc score was 1.7 ± 1.3. "Continuous" warfarin or dabigatran was administered in 80 and 32 % of patients, respectively. Time to first dose of dabigatran post-procedure was 12.2 ± 10.3 h. Two dabigatran and no warfarin-treated patients had systemic thromboembolism (p = NS); five dabigatran and three warfarin-treated patients had bleeding complications (p = NS, combined endpoint p = 0.116). One dabigatran patient had severe pericardial bleeding (3 L blood loss). CONCLUSIONS: In a retrospective pilot trial comparing the risks of systemic thromboembolism or bleeding complications in patients treated with warfarin or dabigatran anticoagulation, the outcomes were similar. A prospective trial is warranted.