The burden of alcohol-related cardiovascular complications in young and middle-aged adults: rising burden of atrial fibrillation and hypertensive heart disease.

BACKGROUND AND AIMS: The burden of alcohol-related complications is high and rising. However, there are notable deficiencies in comprehensive epidemiological study focusing on cardiovascular complications from alcohol, especially among young and middle-aged adults. We thus aimed to determine the burden of these conditions in young and middle-aged adults globally. METHODS AND RESULTS: We used data from the Global Burden of Disease Study 2019 and analysed the mortality and disability-adjusted life years of alcohol-associated cardiovascular complications in young and middle-aged adults. The findings were classified by sex, region, country, and Sociodemographic Index (SDI). The highest age-standardized death rates (ASDR) were observed in stroke 0.84 (95% UI 0.60-1.09), followed by alcoholic cardiomyopathy 0.57 (95% UI 0.47-0.66) per 100,000 population. The overall burden of alcohol-associated cardiovascular complications decreased globally but increased in atrial fibrillation and hypertensive heart disease. Regionally, most regions underwent a decrease in ASDR, but an increase was observed in Southeast Asia (+2.82%), Western Pacific (+1.48%), low-middle (+1.81%), and middle SDI (+0.75%) countries. Nevertheless, the ASDR and ASDALYs were highest in Europe. CONCLUSIONS: The impact of alcohol-associated atrial fibrillation and hypertensive heart disease has increased over the last decades. Regarding region, the burden in Europe and the rising burden in Asia, require immediate public health policy to lessen these cardiovascular complications from alcohol in young and middle-aged adults.

Treatment seeking experiences of ACS patients in Yogyakarta, Indonesia during COVID-19 pandemic: A qualitative study.

Delay in treatment seeking is recognized as a major contributor for Acute Coronary Syndrome (ACS) mortality in Indonesia. Despite the significance of timely treatment, decline in admission and delay in presentation of patients with ACS were consistently reported during the COVID-19 pandemic. These suggested that treatment seeking performance of patients during the pandemic might be different from the previous period. This qualitative study aimed to explore treatment seeking behaviour, barriers in seeking medical treatment, and experiences of patients with ACS in Yogyakarta, Indonesia during COVID-19 pandemic. In depth-interviews were carried out with 30 patients, who were hospitalized with ACS at one of the three selected hospitals in Yogyakarta during the pandemic period. Thematic analysis was performed to create vital explanations for treatment seeking practices of patients with ACS during pandemic. Three significant themes were identified: treatment seeking decisions, barriers in seeking medical treatment during COVID-19, and experiencing both good and bad impression from entering and staying in the hospital. The intensity of ACS symptoms and fear of COVID-19 infection dominated the delay in seeking medical treatment. Strict safety measures, religious belief, and fear of ACS helped patients overcome barriers and seek medical treatment during pandemic. ACS patients also had convenient medical care during the pandemic and believed medical staff would provide excellent care to them. However, visit restriction policy could cause psychological discomfort. Increase awareness of ACS symptoms and the risk of delays ACS treatment are essential to support patients' decisions to seek medical helps in a timely manner at any situations including pandemic. Interventions aim at alleviating psychological distress should also be designed and implemented to improve treatment experiences of ACS patients, who sought medical treatment during the pandemic crisis.

Metabolic Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease in Premenopausal Women: Global Trends and Projections to 2040.

OBJECTIVE: To quantify the burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic disorders in premenopausal women. PATIENTS AND METHODS: Between 2010 and 2019, global evaluations of prevalence, mortality, disability-adjusted life years (DALYs), and their age-standardized rate (ASR) were conducted for metabolic conditions such as MASLD, type 2 diabetes mellitus, dyslipidemia, hypertension (HTN), obesity, and polycystic ovarian syndrome. Subgroup assessments were conducted according to geographical regions and the sociodemographic index. The predictive models were established to estimate mortality and DALYs through 2040. RESULTS: In 2019, the most significant ASR of deaths was found in HTN (11.37; 9.52 to 13.45), followed by obesity (10.49; 7.57 to 13.64). In contrast, the greatest ASR of DALYs was attributed to obesity (816.13; 581.41 to 1073.32), followed by HTN (634.73; 536.75 to 744.77). The mortality rates for dyslipidemia (-0.55%) and HTN (-0.72%) have been decreasing over time, but there has been an increase in obesity (+0.58%), type 2 diabetes mellitus (+0.85%), and MASLD (+0.51%). Lower sociodemographic index countries exhibit a higher disability-to-prevalence ratio. In 2040, obesity is predicted to cause the most deaths (+41.59% from 2019). CONCLUSION: The escalating impact of metabolic syndrome, the rising trends in death rates linked to obesity, and the disparities based on region and socioeconomic status in premenopausal women underscore the alarming increase in the global burden of metabolic syndrome.

Trends in Anticoagulant Utilization and Clinical Outcomes for Cancer-Associated Thrombosis: A Multicenter Cohort Study in Thailand's Upper-Middle-Income Country Setting.

PURPOSE: To evaluate anticoagulant trends and clinical outcomes in the management of cancer-associated thrombosis (CAT) within Thailand, an upper-middle-income country (UMIC). METHODS: This multicenter retrospective cohort study included adult patients with cancer diagnosed with venous thromboembolism (VTE) hospitalized in Thailand from 2017 to 2021. Anticoagulants were classified as low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and warfarin. Prescription trends were assessed, and patients were followed for 1 year, or until 2022 to evaluate outcomes. The primary effectiveness outcome was recurrent VTE, whereas the primary safety outcome was major bleeding. Secondary outcomes included net clinical benefit and all-cause mortality. Treatment effects were examined using inverse probability of treatment weighting (IPTW) Cox proportional hazards models. RESULTS: Among 1,611 patients (61.3% female; mean age, 58.8 years; standard deviation, 13.1 years), 86% received LMWH, 10% warfarin, and 4% DOACs. In the study cohort, LMWH prescriptions remained consistent, warfarin use declined, and DOAC prescriptions notably increased. In IPTW analysis, DOACs showed comparable rates of VTE recurrence (weighted hazard ratio [HR], 0.77 [95% CI, 0.22 to 2.70]; P = .679) and major bleeding (weighted HR, 0.62 [95% CI, 0.15 to 2.55]; P = .506) with LMWH. Warfarin had a higher risk of major bleeding (weighted HR, 2.74 [95% CI, 1.12 to 6.72]; P = .028) but a similar rate of VTE recurrence (weighted HR, 1.46 [95% CI, 0.75 to 2.84]; P = .271) compared with LMWH. Secondary outcomes were consistent across groups. CONCLUSION: LMWH remains the primary treatment for CAT, in line with current guidelines. The study highlights the challenges faced in these settings with the continuous use of warfarin. The comparable efficacy and safety of DOACs with LMWH suggest a potential shift in CAT management within UMICs.

From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women.

INTRODUCTION: The burden of alcohol-related complications is considerable, particularly alcohol-associated liver disease and alcohol use disorder (AUD). However, there are deficiencies in comprehensive epidemiological research focusing on these issues, especially among young women who display higher susceptibility to such complications compared with their male counterparts. We thus aimed to determine the global burden of these conditions in this vulnerable group. METHODS: Leveraging data from the Global Burden of Disease Study 2019, we analyzed the prevalence, mortality, and disability-adjusted life years of alcohol-associated cirrhosis (AC), liver cancer from alcohol, and AUD in young women. The findings were categorized by region, nation, and sociodemographic index. RESULTS: The highest age-standardized prevalence rates were observed in AUD (895.96 [95% uncertainty interval (UI) 722.6-1,103.58]), followed by AC (65.33 [95% UI 48.37-86.49]) and liver cancer from alcohol (0.13 [95% UI 0.09-0.19]) per 100,000 people. The highest age-standardized mortality rates were observed in AC (0.75 [95% UI 0.55-0.97]), followed by AUD (0.48 [95% UI 0.43-0.53]) and liver cancer from alcohol (0.06 [95% UI 0.04-0.09]). The highest burdens of AC and AUD were observed in Central Europe, whereas the high-income Asia Pacific had the highest burden of liver cancer from alcohol. DISCUSSION: Throughout the past decade, the trend of AUD varied among regions while the impact of alcohol-associated liver disease has increased, requiring urgent public health strategy to mitigate these complications, particularly in female patients in Europe and the Asia-Pacific region.

Potential drug-drug interactions of frequently prescribed medications in long COVID detected by two electronic databases.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a wide range of acute and chronic complications including long COVID, a well-known chronic sequela. Long COVID often necessitates long-term treatment, which may lead to an increased potential for drug-drug interactions (DDIs). The objective of this study was to assess potential DDIs among frequently prescribed medications in long COVID by using two electronic databases. Sixty frequently prescribed agents were selected from Thailand's National List of Essential Medicine 2022 for potential DDI analysis by Micromedex and Drugs.com. From these databases, 488 potential DDIs were identified. There were 271 and 434 DDI pairs based on Micromedex and Drugs.com, respectively. Among these DDIs, 77 pairs were labeled as contraindicated or major by both databases. The most common mechanisms for these serious interactions are cytochrome P450 (CYP) inhibition (45%), CYP induction (19%), and QT interval prolongation (7.8%). Based on Fleiss' kappa (0.073), there was only slight agreement of the DDI severity classifications between these two databases. In conclusion, a large number of potential DDIs were detected among frequently prescribed medications for long COVID. Health care providers should be aware of these DDIs, particularly those that are deemed as contraindicated or major. These DDIs are most likely to cause significant adverse events in patients with long COVID because polypharmacy is common.

Drug-Related Problems and Pharmacists' Interventions in Hypertensive Outpatients: A Multicenter Prospective Study in 3 Vietnamese Hospitals.

Background: Clinical pharmacists' interventions (PIs) on drug-related problems (DRPs) in Vietnamese hypertensive outpatients are limited. Objectives: The objective was to investigate the prevalence and nature of DRPs, and factors which are likely to have DRPs, types of PIs, and their acceptance rate in 3 Vietnamese hospitals. Method: A prospective interventional study was conducted over a period of 3 months in 3 hospitals (from October 2021 to March 2022). Clinical pharmacists conducted medication reviews after collecting patient information from prescriptions and patient interviewing, and then identified the DRPs and suggested PIs according to the Vi-Med tool. These DRPs and PIs were reviewed by other superior clinical pharmacists and a consensus meeting with 3 cardiologists. Results: Of 381 patients included, 344 (90.23%) experienced 1 or more DRPs. A total of 820 DRPs were identified with an average of 2.15 DRPs per patient and 415 (50.61%) were hypertension-related issues. The most common DRPs identified were "administration mode" (46.34%), "missing indication" (18.05%), "non-conformity indication" (17.80%), and "dosage" (11.95%). Comorbidity (adjusted odds ratio [AOR] = 3.985, 95% CI: 1.597-9.942, P = 0.003) was the predictor of DRPs. Clinical pharmacists provided 739 PIs and 94.45% were accepted by physicians. Conclusion: The results of this study showed that DRPs were very common in hypertensive outpatients and highlighted the role of clinical pharmacists to identify and resolve DRPs through prompt interventions.

Validation and comparison of the stroke prognosis instrument (SPI-II) and the essen stroke risk score (ESRS) in predicting stroke recurrence in Asian population.

BACKGROUND: Currently, there are limited data on the accuracy of available risk scores to predict stroke recurrence in the Asian population. METHOD: A single-center, retrospective cohort study was conducted among patients with acute ischemic stroke during January 2014 - December 2018. Longitudinal data with three years of follow-up among these patients were collected and validated through both electronic and manual chart review. The area under the receiver-operating curve (AUROC) method or C-statistic and calibration plot were used to evaluate and compare the Stroke Prognosis Instrument II (SPI-II) and the Essen Stroke Risk Score (ESRS) in predicting the long-term risk of recurrent ischemic stroke. The predictive performances of the two scores were compared using DeLong's method. RESULTS: The study cohort consisted of 543 patients, including 181 and 362 patients with and without recurrent events. There were no significant differences in mean age and gender between the two groups. Recurrence cases tended to have significant more risk factors compared to those without events. Among cases with recurrent events, 134 (74.03%) and 65.74% (119) cases were classified as high-risk based on SPI-II and ESRS, respectively. The AUROC curve of the SPI-II and ESRS score was 0.646 (95% CI, 0.594-0.697) and 0.614 (95%CI, 0.563-0.665), respectively (p = 0.394). Based on the calibration plot, the SPI-II and ESRS scores showed similar moderate predictive performance on recurrence stroke with a C statistic (95% CI) of 0.655 (95% CI: 0.603-0.707) and 0.631 (95% CI 0.579-0.684), respectively. CONCLUSION: Both ESRS and SPI-II scores had moderate predictive performance in Thai population.

Effects of turmeric (Curcuma longa) supplementation on glucose metabolism in diabetes mellitus and metabolic syndrome: An umbrella review and updated meta-analysis.

AIMS: This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms. METHODS: An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms. RESULTS: Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis. CONCLUSION: CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS. TRIAL REGISTRATION: PROSPERO (CRD42016042131).

Integrating Real-World Evidence in Economic Evaluation of Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation in a Developing Country.

OBJECTIVE: This study aimed to estimate the cost effectiveness of non-vitamin K oral anticoagulants (NOACs) compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) in Thailand where suboptimal anticoagulation control is common. MATERIALS AND METHODS: A hypothetical cohort of 65-year-old patients with NVAF and their disease progression was simulated in the Markov model. The following anticoagulant agents were used: warfarin, dabigatran, rivaroxaban, and apixaban. Warfarin with high, intermediate, and low time in therapeutic ranges (TTR) was used as the three different reference treatments. Baseline clinical events were obtained from a recently published real-world study in Thailand. A lifetime horizon was utilized in this model, and all analyses were performed from societal and healthcare perspectives. The results were reported as incremental cost-effectiveness ratios (ICERs) in 2021 US dollars per quality-adjusted life-year (QALY) gained. The sensitivity analyses were performed to assess the influence of parameter uncertainty. RESULTS: Apixaban was a cost-effective intervention compared with warfarin with low and intermediate TTR groups. In the low TTR group, the ICERs were $779 and $816 per QALY gained from the societal and healthcare perspectives, respectively, and in the intermediate TTR group, the ICERs were $2038 and $3159 per QALY gained from the societal and healthcare perspectives, respectively. Both ICERs were below the accepted willingness-to-pay threshold ($4806) in the context of Thailand's healthcare. CONCLUSIONS: In a developing country where suboptimal anticoagulation control is common, apixaban was the cost-effective alternative to warfarin for patients with both low and intermediate TTR control.

Development and validation of a bleeding risk prediction score for patients with mitral valve stenosis and atrial fibrillation or mechanical heart valves receiving long-term warfarin therapy.

AIMS: This study aimed to develop and validate a new bleeding risk score to predict warfarin-associated major bleeding for patients with mitral valve stenosis with atrial fibrillation (MSAF) or mechanical heart valves (MHV). METHODS: A multicentre, retrospective cohort study was conducted at 3 hospitals in Thailand. Adult patients with MSAF or MHV receiving warfarin for ≥3 months during 2011-2015 were identified. Data collection and case validation were performed electronically and manually. Potential variables were screened using the least absolute shrinkage and selection operator. Multivariate logistic regression analysis using stepwise backward selection was used to construct a risk score. Predictive discrimination of the score was evaluated using the C-statistic. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: There were 1287 patients (3903.41 patient-year of follow-up), with 192 experiencing bleeding (4.92 event/100 patient-year) in the derivation cohort. A new bleeding risk score termed, the HEARTS-60 + 3 score (hypertension/history of bleeding; external factors, e.g., alcohol/drugs [aspirin or nonsteroidal anti-inflammatory drugs]; anaemia/hypoalbuminaemia; renal/hepatic insufficiency; time in therapeutic range of <60%; stroke; age ≥60 y; target international normalized ratio of 3.0 [2.5-3.5]), was developed and showed good predictive performance (C-statistic [95% confidence interval] of 0.88 [0.85-0.91]). In the external validation cohort of 832 patients (2018.45 patient-year with a bleeding rate of 4.31 event/100 patient-year), the HEARTS-60 + 3 score showed a good predictive performance with a C-statistic (95% confidence interval) of 0.84 (0.81-0.89). CONCLUSION: The HEARTS-60 + 3 score shows a potential as a bleeding risk prediction score in MSAF or MHV patients.

Using real world evidence to generate cost-effectiveness analysis of fibrinolytic therapy in patients with ST-segment elevation myocardial infarction in Thailand.

Background: Due to limited access to primary percutaneous coronary intervention for the management of ST-segment elevation myocardial infarction (STEMI) in low-to-middle-income countries (LMICs), fibrinolysis serves as a vital alternative reperfusion therapy. Among fibrinolytic agents, the cost-effectiveness of tenecteplase (TNK) in LMICs as compared to streptokinase (SK) for STEMI management remains unknown. Methods: Cost-effectiveness was analyzed using a hybrid model consisting of short-term analysis (30-days decision tree model) and long-term analysis (Markov model). Both health care provider and societal perspectives over a lifetime horizon with 3% discount rate were considered. Input parameters were obtained from Thailand's national health database, a network meta-analysis and literature review. Outcome measure was an incremental cost-effectiveness ratio (ICER) determined by an incremental cost per quality-adjusted life years (QALY) gain. An ICER of less than $5,590 per QALY gain is considered cost-effective. Series of sensitivity analyses were also performed. Findings: From the societal perspective, TNK increases cost by $827 and increases QALY by 0·173. Thus, the ICER is $4,777 per QALY gained. Similarly, the ICER from health care provider perspective is $4,664 per QALY gained. In the probabilistic sensitivity analysis, using 5,590 USD per QALY as threshold, the probability of TNK being cost-effective was 83% from both perspectives. The most influential parameters were risk ratio of death for treatment with TNK compared to SK and drug cost of TNK. Interpretation: In a resource-limited country like Thailand, tenecteplase is a cost-effective fibrinolytic drug for treatment of STEMI compared to streptokinase. Funding: None.

Effects of pharmacist interventions on cardiovascular risk factors and outcomes: An umbrella review of meta-analysis of randomized controlled trials.

AIMS: To grade the evidence from published meta-analyses of randomized controlled trials (RCTs) that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes. METHODS: MEDLINE, Embase, and the Cochrane Library were searched from database inception to July 2021. Meta-analyses of RCTs were eligible. Quality of evidence were assessed by GRADE approach. RESULTS: From 9308 publications, 149 full-text articles were evaluated for eligibility, and 24 studies with 85 unique meta-analyses that assessed effects of pharmacist intervention on cardiovascular risk factors and cardiovascular outcomes were selected. Overall, 71.7% (61/85) of unique meta-analyses showed significant impacts of pharmacist intervention. For the quality of evidence, 63.4% of meta-analyses had large heterogeneity (I2 > 50%) while 1.2, 16.5, 32.9 and 49.4% of meta-analyses were graded as high, moderate, low and very low quality based on GRADE approach, respectively. Among meta-analyses with moderate quality, pharmacist interventions significantly mitigated risk factors (including 6/3 mmHg reduction of blood pressure, increased the rate of lipid control, glucose control and smoking cessation (pooled odds ratio, [95% confidence interval] 1.91 [1.55, 2.35], 3.11 [2.3, 4.3] and 2.3 [1.33, 3.97], respectively) and improved medication adherence (1.67 [1.38, 2.02]). Furthermore, pharmacist interventions significantly reduced all-cause mortality (0.72 [0.58, 0.89]) and improved quality of life in patients suffering from chronic heart failure. CONCLUSION: This umbrella review found convincing evidence that pharmacist intervention can provide a wide range of benefits in cardiovascular disease management, ranging from risk factor control, improvement in medication adherence and, in some settings, reduction in morbidity and mortality.

Comparison of the HAS-BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct-acting oral anticoagulants.

AIMS: This study aimed to evaluate the performance of HAS-BLED and ORBIT scores in predicting bleeding risk among Asian patients with nonvalvular atrial fibrillation (NVAF) using direct-acting oral anticoagulants (DOACs). METHODS: A retrospective chart review was conducted among adult patients receiving DOACs for ≥6 months during January 2013 to December 2017 in 10 tertiary care hospitals in Thailand. The area under the receiver operating curve (AUROC) method or C-statistic was used to test the diagnostic accuracy for bleeding risk classification of HAS-BLED and ORBIT scores. The predictive performances of the two scores were compared using DeLong's method. RESULTS: A total of 961 NVAF patients, 52.5% warfarin-naïve and 47.5% warfarin-experienced, with mean age of 74.25 ± 10.08 years, were included in the analysis. Mean HAS-BLED and ORBIT scores of the cohort were 1.98 ± 1.10 and 2.37 ± 1.71, respectively. During the mean follow-up time of 1.55 ± 1.13 years, 34 patients experienced major bleeding (2.28 events/100 patient-year). For the overall cohort, both the HAS-BLED and ORBIT scores showed similarly moderate predictive performance on bleeding with C-statistic (95% confidence interval) of 0.65 (0.57-0.74) and 0.64 (0.56-0.71), respectively. There was no statistical significance between the two scores (P = .62). Analysis based on the status of previous warfarin use was consistent with the overall cohort. Based on the calibration analysis, both HAS-BLED and ORBIT scores possessed moderate ability to identify those who experienced major bleeding from those who did not. CONCLUSION: Both HAS-BLED and ORBIT bleeding risk scores had moderate predictive performance in Asian NVAF patients receiving DOACs.

Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVES: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs). DESIGN: Systematic review and meta-analysis. SETTING: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019. PARTICIPANTS: Patients with AF. MAIN OUTCOME MEASURES: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist. RESULTS: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I2=59.9%), $6353.24 ($4076.03 to $8630.45; I2=0%), $7664.58 ($2979.79 to $12 349.37; I2=0%) and $8573.07 ($1877.05 to $15 269.09; I2=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I2=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs. CONCLUSIONS: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP. PROSPERO REGISTERATION NUMBER: CRD 42019146610.

Prospective randomised trial examining the impact of an educational intervention versus usual care on anticoagulation therapy control based on an SAMe-TT2R2 score-guided strategy in anticoagulant-naïve Thai patients with atrial fibrillation (TREATS-AF): a study protocol.

INTRODUCTION: The burden of atrial fibrillation (AF) in Thailand is high and associated with increased morbidity, mortality and healthcare costs. Vitamin K antagonists (eg, warfarin), commonly used for stroke prevention in patients with AF in Thailand, are effective but are often suboptimally controlled. We aim to evaluate the impact of an SAMe-TT2R2 score-guided strategy and educational intervention compared to usual care on anticoagulation control expressed by the time in therapeutic range (TTR) at 12 months, in anticoagulant-naïve Thai patients with AF. METHODS AND ANALYSIS: Multicentre, open-label, parallel-group, randomised controlled trial conducted in Thailand among adult patients (age: 18 years) with AF who are anticoagulant naïve. Patients will be randomised to one of two groups; an SAMe-TT2R2 score-guided strategy with educational intervention and usual care versus usual care alone. The planned follow-up period is 12 months. The primary outcome is TTR at 12 months. Secondary outcomes include: (1) TTR at 6 months; (2) thromboembolic and bleeding events at 12 months; (3) composite major adverse cardiovascular events at 12 months; (4) change in patients' knowledge of AF between baseline and 6 months and 12 months; (5) cost effectiveness; (6) quality of life at baseline, 6 months and 12 months using EQ-5D-5L (Thai version) and (7) patient satisfaction/perceptions of the TREAT intervention. An embedded qualitative study will assess patient perceptions of the TREAT intervention. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Review Committee, Ministry of Public Health of Thailand, and registered in the Thai Clinical Trials Registry. The results of this trial will be submitted for publication in a peer-reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided to all participants prior to publication. TRIAL REGISTRATION NUMBER: TCTR20180711003.

Real-world experience of angiotensin receptor/neprilysin inhibitor (ARNI) usage in Thailand: a single-center, retrospective analysis.

BACKGROUND: Treatment of heart failure with reduced ejection fraction (HFrEF) has been revolutionized by angiotensin receptor/neprilysin inhibitor (ARNI). ARNI has been shown to significantly reduce morbidity and mortality in a large, randomized controlled trial. However, real-world evaluation of ARNI with a diverse population is still limited. METHODS: HFrEF patients receiving angiotensin receptor/neprilysin inhibitor (ARNI) or standard HF treatment at a university hospital in Thailand were prospectively followed-up from January 2015 to December 2019. The primary outcome was a composite of all-cause mortality and heart failure hospitalization. Survival analysis and the Cox proportional hazard model were used to compare clinical outcomes between the two groups. RESULTS: During a follow-up period of 12 months, the primary outcome occurred in 10 patients in the ARNI group (11.5%) and 28 in the standard treatment group (28.0%) (hazard ratio 0.34; 95% CI: 0.15-0.80; p = 0.013). After adjustment for confounding factors, ARNI was significantly associated with a significant reduction in the primary outcome (HR 0.32, 95% CI: 0.13-0.82, p = 0.017). In addition, ARNI was also significantly associated with a decrease in the clinical signs and symptoms of HF, including dyspnea, orthopnea, and fatigue. Orthostatic hypotension was more frequently reported among the ARNI group than among the standard treatment group. The rates of target dose achievement were comparable between the two groups. CONCLUSION: In real-world practice, ARNI use was associated with a significant reduction in both clinical outcomes and symptom improvement, while orthostatic hypotension was more common in patients in the ARNI group than in patients in the standard treatment group.

A systematic review and meta-analysis of randomized controlled trials of cardiovascular toxicity of medical cannabinoids.

BACKGROUND: Several systematic reviews (SRs) have summarized the potential effectiveness of medical cannabinoids, but it is unclear to what extent safety-related outcomes were incorporated. OBJECTIVE: The objective of this study was to evaluate the cardiovascular toxicity associated with medical use of cannabinoids. METHODS: A 2-stage systematic review (SR) approach was undertaken to assess the current evidence on cannabinoid-associated cardiovascular events reported among randomized controlled trials (RCTs). First, we searched for SRs in multiple sources until June 2019. Second, RCTs identified from the SRs were included if they assessed medical cannabis and reported cardiovascular events. The outcomes of interest were all types of cardiovascular events. Data were extracted by 2 independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 47 studies involving 2800 patients were included. The median duration of cannabinoid use was 15.8 days (range 1 to 322), and 45% of the studies excluded patients with underlying cardiovascular diseases. Cannabinoid use was significantly associated with increased risks of orthostatic hypotension (RR 3.16 [95% CI 2.27-4.40], I2 = 2.3%) and hypotension (3.55 [1.45-8.71], I2 = 31.8%), with a trend of increased risk of tachycardia (1.94 [0.81-4.64], I2 = 48.6%). No study reported serious cardiovascular events. CONCLUSIONS: Cannabinoid use was associated with tachycardia, hypotension, and orthostatic hypotension. There is a paucity of data for other cardiovascular events among medical cannabis users. More data, especially regarding long-term effects among patients with existing cardiovascular diseases, are needed.

Effect of tomato, lycopene and related products on blood pressure: A systematic review and network meta-analysis.

BACKGROUND: A number of randomized controlled trials (RCTs) have been conducted to evaluate the hypotensive effects of tomato, lycopene, and related products. However, the findings were conflicting, partly due to differences in the types of products investigated. Therefore, this study aimed to assess and compare the hypotensive effects of different tomato-related preparations through a network meta-analysis based on randomized controlled trials. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: A network meta-analysis based on a systematic review of RCTs comparing the effect of various tomato, lycopene and related products versus placebo on blood pressure in adults was performed. PubMed, EMBASE, SCOPUS, and Clinicaltrial.gov databases were searched up to October 2020 without language restrictions. The primary outcomes were systolic and diastolic blood pressure. Mean differences (MDs) along with 95% confidence intervals (CIs) were estimated and pooled using a random-effects model. Heterogeneity was assessed using the global inconsistency test. RESULTS: A total of 11 studies including six forms of tomato, lycopene and related products met the inclusion criteria. Among these trials, eight (N = 617) and seven trials (N = 501) were included in the analysis of systolic (SBP) and diastolic blood pressure (DBP) outcomes, respectively. The standardized tomato extract (STE) significantly decreased SBP compared to placebo, with a pooled MD (95% CI) of -5.89 (-9.13 to -2.64) mmHg. The effect on DBP was not significant, with a pooled MD (95% CI) of -3.51 (-7.39 to 0.38) mmHg. Subgroup analysis in hypertensive patients showed that STE significantly reduced both SBP and DBP with pooled MDs (95% CIs) of -8.09 (-11.52 to -4.67) and -4.25 (-6.97 to -1.53) mmHg, respectively, compared to placebo. Other forms of tomato, including other dose ranges of standardized tomato extract, tomato-containing diet, lycopene-free preparation, and synthetic lycopene, did not show consistent and significant effects on either SBP or DBP in all analyses. CONCLUSION: Standardized tomato extract (STE) significantly decreased SBP compared to placebo in a mixed population of healthy volunteers and hypertensive patients. The BP-lowering effect was more pronounced among hypertensive patients. No significant BP effects were seen with other forms of tomato, lycopene and related products in the overall population or any subgroup of the population.

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.