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.

Prescriber compliance to direct oral anticoagulant labels and impact on outcomes in Thailand.

AIMS: This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes. METHODS: A retrospective study was conducted using simple-stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013-2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration-approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events. RESULTS: From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off-label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291-7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501-6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083-4.452; P = .029). CONCLUSION: Prescribers' compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.

Real-World Comparative Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants vs. Warfarin in a Developing Country.

We aimed to compare effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin for stroke prevention in nonvalvular atrial fibrillation (NVAF) in a developing country where anticoagulation control with warfarin is suboptimal. A real-world study was conducted among patients with NVAF in Thailand receiving NOACs and warfarin from 9 hospitals during January 2012 to April 2018. Propensity-score weighting was used to balance covariates across study groups. Cox regression models were used to compare the risk of thromboembolism, major bleeding, and net adverse clinical events across matched cohorts. A total of 2,055 patients; 605, 604, 441, and 405 patients receiving warfarin, rivaroxaban, dabigatran, and apixaban, respectively, were included. Median (interquartile range) time in therapeutic range (TTR) for warfarin users was 49.5% (26.6%-70.3%). Compared with warfarin, NOACs were associated with a significant reduction in major bleeding either when analyzed as a group (adjusted hazard ratio (HR) (95% confidence interval (CI)) of 0.46 (0.34-0.62) or by each agent. Compared with warfarin users with poor TTR, apixaban (adjusted HR 0.48, 95% CI 0.26-0.86, P = 0.013) and dabigatran (adjusted HR 0.44, 95% CI 0.21-0.90, P = 0.025) were associated with a lower risk of thromboembolism, in addition to markedly lower risk of major bleeding. In a healthcare system where anticoagulation control with warfarin is suboptimal, use of NOACs was associated with a profound reduction in major bleeding. The effectiveness and safety advantages of NOACs were more pronounced compared with warfarin users with low TTR.

Clinical Predictors Influencing the Length of Stay in Emergency Department Patients Presenting with Acute Heart Failure.

Background and objectives: Acute heart failure is a common problem encountered in the emergency department (ED). More than 80% of the patients with the condition subsequently require lengthy and repeated hospitalization. In a setting with limited in-patient capacity, the patient flow is often obstructed. Appropriate disposition decisions must be made by emergency physicians to deliver effective care and alleviate ED overcrowding. This study aimed to explore clinical predictors influencing the length of stay (LOS) in patients with acute heart failure who present to the ED. Materials and Methods: We conducted prognostic factor research with a retrospective cohort design. Medical records of patients with acute heart failure who presented to the ED of Ramathibodi Hospital from January to December 2015 were assessed for eligibility. Thirteen potential clinical predictors were selected as candidates for statistical modeling based on previous reports. Multivariable Poisson regression was used to estimate the difference in LOS between patients with and without potential predictors. Results: A total of 207 patients were included in the analysis. Most patients were male with a mean age of 74.2 ± 12.5 years. The median LOS was 54.6 h (Interquartile range 17.5, 149.3 h). From the multivariable analysis, four clinical characteristics were identified as independent predictors with an increase in LOS. These were patients with New York Heart Association (NYHA) functional class III/IV (+72.9 h, 95%Confidence interval (CI) 23.9, 121.8, p = 0.004), respiratory rate >24 per minute (+80.7 h, 95%CI 28.0, 133.3, p = 0.003), hemoglobin level <10 mg/dL (+60.4 h, 95%CI 8.6, 112.3, p = 0.022), and serum albumin <3.5 g/dL (+52.8 h, 95%CI 3.6, 102.0, p = 0.035). Conclusions: Poor NYHA functional class, tachypnea, anemia, and hypoalbuminemia are significant clinical predictors of patients with acute heart failure who required longer LOS.

Use of the CRUSADE bleeding risk score in the prediction of major bleeding for patients with acute coronary syndrome receiving enoxaparin in Thailand.

BACKGROUND: CRUSADE risk score stands out as a simple-to-use bleeding risk model. However, its use is still doubtful for Thai population. The aim of this study was to assess the prognostic value of CRUSADE in predicting risk of major bleeding among Thai patients with acute coronary syndrome (ACS) receiving enoxaparin. METHODS: A retrospective cohort study was performed using patients with ACS who were hospitalised at a university hospital in Bangkok between 2006 and 2009 and had received enoxaparin. The CRUSADE risk score was calculated. The model validation was tested by using C statistic and Hosmer-Lemeshow goodness-of-fit. RESULTS: The overall incidence of major bleeding was 18.3%. Median CRUSADE score for entire study population, unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI) were 49, 47, 53, and 39, respectively. Hosmer-Lemeshow goodness of fit revealed no statistical significance in all groups. The CRUSADE model demonstrated a satisfactory discriminatory capacity for the entire study population (C = 0.688), UA (C = 0.591), NSTEMI (C = 0.693), and STEMI groups (C = 0.736). CONCLUSIONS: Across the ACS spectrum, CRUSADE risk score was able to estimate in-hospital major bleeding of Thai patients with ACS who received treatment with enoxaparin. The application of these results in Thailand may be helpful in the identification of patients at high bleeding risk and also may lead to implementation of appropriate prevention.

Fragmented QRS as a Predictor of Appropriate Implantable Cardioverter-defibrillator Therapy.

BACKGROUND: Fragmented QRS (fQRS) has been shown to be a marker of local myocardial conduction abnormalities and a predictor of cardiac events in selected populations. We hypothesized that the presence of a fQRS might predict arrhythmic events in patients who received an implantable cardioverter-defibrillator (ICD), regardless of the indications for implantation. METHODS AND RESULTS: A cohort of 107 consecutive patients (mean age, 53 years; 82% male) who underwent an ICD implantation was studied. We defined fQRS, on a routine 12-lead ECG, as the presence of an additional R wave or notching in the nadir of the S wave in 2 consecutive leads corresponding to a major coronary artery territory. In the presence of bundle branch block, more than 2 notches in the R or S waves in 2 consecutive leads were required to characterize fQRS. Patients were followed for 21.3±23 months for appropriate ICD therapy (antitachycardia pacing and/or shock). ICDs were implanted predominantly in patients with ischemic cardiomyopathy (N=45, 42.1%), followed by Brugada syndrome (N=26, 24.3%). fQRS presented in 42 patients (39.3%). During follow-up, patients with fQRS received more appropriate ICD therapy than those without fQRS (45.2% vs. 10.8%, P<0.0001). After adjustment for covariates, fQRS remained an independent predictor for appropriate ICD therapy (hazard ratio=5.32, 95% confidence interval=2.11-13.37, P<0.0001). CONCLUSION: The presence of fQRS appeared to be directly associated with appropriate ICD therapy.

Aggregatibacter actinomycetemcomitans serotypes, the JP2 clone and cytolethal distending toxin genes in a Thai population.

AIM: To examine the genetic diversity of Aggregatibacter actinomycetemcomitans in Thai adults. MATERIALS AND METHODS: Subgingival plaque samples from 453 subjects were analysed for A. actinomycetemcomitans serotypes, the presence of the high leukotoxin-producing JP2 clone and cytolethal distending toxin genes (cdtABC) using the polymerase chain reaction technique. In subjects who were positive for cdtABC, restriction fragment length polymorphism analysis was used to identify a single nucleotide polymorphism (SNP) in the cdtB gene at amino acid position 281. The extent and severity of periodontal disease were compared between subjects harbouring different A. actinomycetemcomitans genotypes. RESULTS: Eighty six subjects (19%) were positive for A. actinomycetemcomitans. The JP2 clone was not detected. Serotype c was the most prevalent (57%), followed by serotypes a (33%) and b (7%). Among A. actinomycetemcomitans-positive subjects, 27% were positive for cdtABC. All cdtABC-positive subjects possessed the SNP in the cdtB, which is involved with increased toxin activity. The presence of A. actinomycetemcomitans, but not a specific genotype, was significantly related to increased probing depth and periodontal attachment loss. CONCLUSIONS: Our results confirm the previous findings that genotype distribution of A. actinomycetemcomitans varies between ethnic groups. However, no clear relationship between a specific genotype and periodontal conditions was observed.

Association between cigarette smoking and the intraoral distribution of periodontal disease in Thai men over 50 years of age.

AIM: This study aimed to investigate the effects of cigarette smoking on periodontal conditions in specific tooth regions of older Thai men. METHODS: There were 272 current smokers, 714 former smokers, and 477 non-smokers enrolled in the present study. Differences between groups in the mean probing depth or attachment loss were compared using ancova. The relationship between smoking exposure or cessation duration and periodontal conditions was examined using linear trend analysis. RESULTS: Smokers had deeper pockets and attachment loss than non-smokers. The greatest differences between smokers and non-smokers were observed in the maxillary posterior palatal region, where current smokers had 0.88 mm greater attachment loss than non-smokers, compared to 0.36-0.60 mm observed in other tooth regions. Among the current smokers, there was a trend towards an increase in attachment loss with increasing smoking exposure in the maxillary posterior regions. However, it was not statistically significant. Among the former smokers, a better periodontal condition was observed, depending on the length of time since smoking cessation; this was most pronounced in the maxillary posterior palatal region. CONCLUSIONS: The palatal site of maxillary posterior teeth was the area most affected by cigarette smoke. The results suggest a possible local effect of smoking in addition to its systemic effects.

Attributable Cost and Length of Stay for Patients with Enoxaparin-Associated Bleeding.

OBJECTIVES: Patients receiving enoxaparin are at risk of bleeding. The study of the economic impact of enoxaparin-associated bleeding in Asian population, however, is limited. This study aimed to estimate the attributable costs and length of stay (LOS) of patients experiencing enoxaparin-associated bleeding compared with nonbleeding patients in the setting of acute coronary syndrome. METHODS: We conducted a retrospective cohort study of hospitalized patients with acute coronary syndrome who received enoxaparin in a large university-affiliated hospital. Cost and LOS were compared among three groups of patients according to the status of bleeding event. The attributable cost and LOS were estimated by using multiple linear regressions with log-transformed model and adjusted by confounders. The adjusted means of cost and LOS estimates were retransformed to their natural values by using Duan's smearing estimator. The differences of costs and LOS were presented as mean with 95% confidence intervals (CIs). RESULTS: Out of 346 patients, 134 experienced enoxaparin-associated bleeding (28 and 106 patients experienced major and minor bleeding, respectively). The average age and gender in both groups were similar. Compared to the nonbleeding group, the attributable cost and LOS were 108,226 Thai baht (95% CI: 87,068-129,386) and 8 days (95% CI: 7.1-9.0) for major bleeding and 72,997 Thai baht (95% CI: 57,822-88,172) and 3.1 days (95% CI: 2.5-3.7) for minor bleeding, respectively. CONCLUSIONS: Bleeding is significantly associated with increased cost and LOS among enoxaparin users. These findings suggest that strategies aiming to reduce bleeding events may potentially help reduce the cost of care among patients with acute coronary syndrome receiving enoxaparin therapy.

Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium.

BACKGROUND: The underlying electrophysiological mechanism that causes an abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (Vt/VF) in patients with the Brugada syndrome (BrS) remains unelucidated. However, several studies have indicated that the right ventricular outflow tract (RVOT) is likely to be the site of electrophysiological substrate. We hypothesized that in patients with BrS who have frequent recurrent VF episodes, the substrate site is the RVOT, either over the epicardium or endocardium; abnormal electrograms would be identified at this location, which would serve as the target site for catheter ablation. METHODS AND RESULTS: We studied 9 symptomatic patients with the BrS (all men; median age 38 years) who had recurrent VF episodes (median 4 episodes) per month, necessitating implantable cardioverter defibrillator discharge. Electroanatomic mapping of the right ventricle, both endocardially and epicardially, and epicardial mapping of the left ventricle were performed in all patients during sinus rhythm. All patients had typical type 1 Brugada ECG pattern and inducible Vt/VF; they were found to have unique abnormal low voltage (0.94±0.79 mV), prolonged duration (132±48 ms), and fractionated late potentials (96±47 ms beyond QRS complex) clustering exclusively in the anterior aspect of the RVOT epicardium. Ablation at these sites rendered Vt/VF noninducible (7 of 9 patients [78%]; 95% confidence interval, 0.40 to 0.97, P=0.015) and normalization of the Brugada ECG pattern in 89% (95% confidence interval, 0.52 to 0.99; P=0.008). Long-term outcomes (20±6 months) were excellent, with no recurrent Vt/VF in all patients off medication (except 1 patient on amiodarone). CONCLUSIONS: The underlying electrophysiological mechanism in patients with BrS is delayed depolarization over the anterior aspect of the RVOT epicardium. Catheter ablation over this abnormal area results in normalization of the Brugada ECG pattern and prevents Vt/VF, both during electrophysiological studies as well as spontaneous recurrent Vt/VF episodes in patients with BrS.

Lipid-lowering treatment in hypercholesterolemic patients: the CEPHEUS Thailand survey.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) has become the leading cause of death and disability in Thailand. Low-density lipoprotein cholesterol is the major risk factor of this condition that can be intervened by means of lifestyle modification and pharmacologic treatment. Adequacy of hypercholesterolemia treatment with lipid lowering drugs in Thailand needed to be more clarified. The present study was conducted to determine low-density cholesterol goal attainment in Thai population at risk for developing ASCVD. MATERIAL AND METHOD: Twenty-seven physicians with their 909 hypercholesterolemic patients whose age of > or = 18 years, actively under pharmacologic treatment for at least three months with no dose adjustment for a minimum of six weeks from seven centers across Thailand were enrolled. Plasma glucose, total cholesterol, LDL cholesterol, HDL-cholesterol, and triglyceride levels were measured after overnight fast. Demographic and other relevant data including information on lipid lowering drug used were retrieved. Patients' awareness, knowledge on their management, compliance, and satisfaction were evaluated by questionnaire survey as well as physicians' use of guidelines, choice of management and goal setting, and their attitudes towards lipid management. Cardiovascular risk level and LDL goal were assessed by the updated 2004 NCEP-ATP III guidelines. RESULTS: All patients had LDL goal of < 130 mg/dl with 86.1% needed LDL goal of < 100 mg/dL. Overall, 52.7% of the patients reached their LDL goal. The most prescribed treatment was statin monotherapy (82.7%). LDL goal attainment was inversely associated with LDL goal set by NCEP-ATP III according to the patients' risk profile, with only 16.7% of those who were in the very high risk group with LDL goal of < 70 mg/dL achieved their goal whereas 60.6% and 84.7% of those with high (LDL goal < 100 mg/dl) and moderately high-risk (LDL goal < 130 mg/dl) achieved their goal, respectively (p < 0.001). Other factors associated with less favorable LDL goal attainment were coronary heart disease, carotid artery disease, diabetes, 10-year risk of > 20%, and metabolic syndrome (p < 0.05 for all). Type of lipid lowering drug was not significantly associated with LDL goal attainment. CONCLUSION: LDL goal attainment was not achieved in a high proportion of Thai patients especially in those who had high to very high risk for developing cardiovascular disease. Despite availability of well-established treatment guideline and efficacious lipid lowering drugs, many patients still miss the opportunity to effectively control their lipid profile.

Feasibility, efficacy, and safety of radiofrequency catheter ablation for cardiac arrhythmias: a twelve-year experience in Thailand.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is widely accepted as a curative treatment for many types of cardiac arrhythmias. MATERIAL AND METHOD: The authors retrospectively reviewed 1,193 cases (mean age 45, 41% male) performed in the electrophysiology laboratory at Ramathibodi Hospital from 1996 to 2007. Success rate, recurrence rate and complications were analyzed. RESULTS: Ablations of atrioventricular nodal reentrant tachycardia (AVNRT, 428 cases, 35.9%) and atrioventricular reentrant tachycardia (AVRT, 346 cases, 29%) were the most common procedures. The overall success rate and recurrence rate of RFCA were 88.8% and 6.1% respectively. Complications occurred in 50 patients (4.2%) with 1 death (0.08%). RFCA of AVNRT or AVRT rather than other arrhythmias (Odd ratio 11.46, 95% confidence interval 8.14-16.15, p < 0.001) and adult rather than pediatric patients (Odd ratio for age 1.007, 95% confidence interval 1.003-1.011, p < 0.001) were independent predictors for successful RFCA. CONCLUSION: RFCA of cardiac arrhythmia in our institution is safe and effective.

Relationship between the presence of certain bacterial pathogens and periodontal status of urban Thai adults.

BACKGROUND: The association between Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T. forsythensis) and periodontal disease has been reported in Western populations. However, corresponding data in Asian populations are still lacking. The aim of this study was to determine the prevalence of these three bacteria and their relationship to periodontal status in a group of urban Thai adults. METHODS: The study was conducted in 453 subjects, aged 39 to 59 years. The presence of bacteria in subgingival plaque was analyzed using polymerase chain reaction analysis. Subjects were classified as having chronic periodontitis if they had at least three sites with probing depths > or =5 mm. Logistic regression analysis was used to determine the degree of association between the target bacteria and periodontal status. RESULTS: A. actinomycetemcomitans, P. gingivalis, and T. forsythia were found in 19.0%, 70.9%, and 77.5% of the subjects, respectively. About one-third (36.2%) of subjects had chronic periodontitis. In univariate analysis, age, male gender, current smoking, diabetes, and the presence of A. actinomycetemcomitans or P. gingivalis were positively associated with chronic periodontitis, whereas education and income exhibited inverse associations with chronic periodontitis. In multivariate analysis, education, current smoking, diabetes, and the presence of A. actinomycetemcomitans and P. gingivalis remained significant. The adjusted odds ratios for having chronic periodontitis were 2.5 and 3.4 in subjects positive for A. actinomycetemcomitans and P. gingivalis, respectively. However, no significant association was observed between the presence of T. forsythia and periodontal status. CONCLUSION: The presence of A. actinomycetemcomitans and P. gingivalis, but not T. forsythia, in subgingival plaque was associated with chronic periodontitis in this group of Thai adults.

Chryseobacterium meningosepticum infection and cardiac tamponade in a long-term hemodialysis patient.

Chryseobacterium meningosepticum is a lactose-nonfermenting gram-negative bacilli ubiquitously found in the natural and hospital environment. Clinical infection caused by C. meningosepticum is very rare among healthy adults. We present the case of a patient with end-stage renal disease who developed purulent pericarditis with C. meningosepticum infection, which rapidly evolved into cardiac tamponade and death. To our knowledge, this is the first case in which C. meningosepticum caused fatal purulent pericarditis in a hemodialysis patient.

Correction of hypercoagulability and amelioration of pulmonary arterial hypertension by chronic blood transfusion in an asplenic hemoglobin E/beta-thalassemia patient.

Chronic transfusion of packed red blood cells, in addition to other ongoing treatment with warfarin, acetyl salicylic acid, desferrioxamine, and other supportive measures, was given to a splenectomized hemoglobin E/beta-thalassemia woman with pulmonary arterial hypertension (PHT). Serial measurements of plasma thrombin-antithrombin III complex (TAT) levels and right-sided cardiac catheterization were used to monitor changes after treatment. Reduction of plasma TAT levels from 7.5 to 3.8 microg/L (normal, 3 +/- 2.4 microg/L), pulmonary vascular resistance (PVR) from 553.8 to 238.6 dyne.sec.cm(-5) (normal, 67 +/- 30 dyne.sec.cm(-5)), and mean pulmonary arterial pressure from 51 to 32 mm Hg (normal, 9 to 19 mm Hg) occurred in tandem. Normalization of blood hypercoagulability as reflected in plasma TAT level by chronic blood transfusion was the likely basis for improvement of increased PVR, being secondary to thrombotic pulmonary arteriopathy and subsequently PHT.

Pulmonary arterial hypertension in previously splenectomized patients with beta-thalassemic disorders.

Our aim was to study the cause and describe the clinical features of pulmonary arterial hypertension (PHT) in splenectomized beta-thalassemia (beta-Thal) patients. Ten splenectomized beta-Thal patients with systolic pulmonary artery (PA) pressure >30 mm Hg were evaluated by echocardiography, right-heart catheterization, and pulmonary angiography. Five of these patients later underwent hemodynamic studies. Echocardiography and pulmonary angiography on the 10 patients showed normal values of left ventricular systolic function and no findings of acute or chronic pulmonary embolism. Hemodynamic evaluation showed very high PA pressures associated with markedly increased pulmonary vascular resistance indices (PVRIs). Hematological evaluation of the 10 patients showed marked anemia, markedly increased numbers of nucleated red blood cells (nRBCs), and serum ferritin. Mean platelet count, plasma beta2 thromboglobulin, and thrombin-antithrombin III complex levels were significantly increased. It was concluded that PHT can be found in splenectomized beta-Thal patients. Features associated with PHT were female sex, hemoglobin E/beta-Thal, status many years postsplenectomy, marked anemia, markedly increased nRBC count, thrombocytosis, and very high serum ferritin levels. PHT was not due to pulmonary emboli. Our findings suggested that severe PHT was due to increased PVRI from thrombotic pulmonary arteriopathy, likely from chronic low-grade hypercoagulability and platelet activation after splenectomy.

Defibrillator Versus beta-Blockers for Unexplained Death in Thailand (DEBUT): a randomized clinical trial.

BACKGROUND: Sudden Unexplained Death Syndrome (SUDS) is the leading cause of death in young, healthy, Southeast Asian men. The role of an implantable cardioverter defibrillator (ICD) for mortality reduction in these patients remains unclear. METHODS AND RESULTS: The Defibrillator Versus beta-Blockers for Unexplained Death in Thailand (DEBUT) study is a randomized, clinical trial conducted in 2 phases (pilot study followed by the main trial) to compare the annual all-cause mortality rates among SUDS patients treated with beta-blockers versus that among those treated with an ICD. A total of 86 patients who were SUDS survivors and probable SUDS survivors were randomized to receive an ICD or propranolol (20 patients were in the pilot study and 66 were in the main trial). The primary end point was death from all causes. The secondary end point was recurrent ventricular tachycardia/ventricular fibrillation (VF) or cardiac arrest. During the 3-year follow-up period of the main trial, there were 4 deaths; all occurred in the beta-blocker group (P=0.02). Seven subjects in the ICD arm had recurrent VF, and all were effectively treated by the ICD. On the basis of the main trial results, the Data Safety Monitoring Board stopped the study. In total (both from the Pilot study and the main trial), there were 7 deaths (18%) in the beta-blocker group and no deaths in the ICD group, but there were a total of 12 ICD patients receiving ICD discharges due to recurrent VF. CONCLUSIONS: ICD treatment provides full protection from death related to primary VF in a SUDS population and is superior to beta-blockade treatment.