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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.

Purpose This study aimed to describe incidence, risk factors, and outcomes of warfarin‐associated major bleeding (WAMB) in Thai patients. Method A nested case‐control study was conducted in a cohort of adult patients receiving ≥6 months of warfarin therapy who were prospectively followed up at a tertiary care hospital in Thailand during January 2011 to December 2014. Logistic regression was used to identify risk factors associated with WAMB. The area under the receiver operating characteristic (AUROC) curve was used to assess the performance of the HAS‐BLED score to predict WAMB in patients with non‐valvular atrial fibrillation (NVAF). Results Among 1604 patients (2972 patient‐year of follow‐up), there were 93 major bleeding that occurred in 76 patients. The incidence of WAMB was 3.13 events per 100 patient‐year. Time in therapeutic range (TTR) of <60% (RR: 3.62, 95% CI: 1.94‐6.73, P < 0.001), mechanical valve replacement at mitral position (RR 3.43, 95% CI: 1.92‐6.16, P < 0.001) cancer (RR: 2.84, 95% CI: 1.11‐7.29, P = 0.029), and age ≥ 65 years (RR: 2.37, 95% CI: 1.20‐4.67, P = 0.012) were independent risk factors for WAMB. There were 17 fatalities and 12 cases of disabilities from WAMB. Mean cost of WAMB was 45 341.54 THB/event. An exploratory analysis suggested that HASBLED score demonstrated an excellent discriminatory capacity to predict WAMB among NVAF patients (AUROC of 0.91, 95% CI: 0.85‐0.97, P < 0.001). Conclusion WAMB in Thai population is common and associated with high rate of morbidity and mortality. Improvement in anticoagulation control is clearly needed.

Background Heart failure (HF) has become a significant health burden in developing countries where anemia is highly prevalent. Limited data exists on the effects of anemia on HF in these population. Methods A retrospective observational study was conducted in all adult patients hospitalized due to HF at Buriram Hospital in Thailand, during July 2010 to June 2015. Survival analysis was performed to evaluate the impact of anemia on 1- year all-cause mortality for the overall cohort, patients with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Results A total of 414 HF patients including 287 HFpEF patients (69.3%) and 127 HFrEF patients (30.7%) were included in our analysis. Mean age was 62.51 ± 14.89 years, with 55% female. Overall prevalence of anemia in HF was 62.6% (259 patients). One-year all-cause mortality was significantly higher in patients with anemia than in non-anemia groups (20.08% vs 12.26%, p = 0.041). When analyzed based on types of HF, anemia significantly increased mortality risk in HFpEF group [adjusted hazard ratio (HR) 2.667, 95%CI, 1.216–5.853, p = 0.014] but not with HFrEF group (adjusted HR 0.901, 95%CI, 0.376–2.155, p = 0.804). The mortality of anemic patients who were left untreated was significantly higher than those who were treated (adjusted HR 2.13, 95%CI, 1.13–3.99, p = 0.027). Conclusion Anemia significantly increased mortality in HF patients, especially among HFpEF. Attempts to identify, diagnose and manage anemia should be integrated in HF care plan in developing countries with high prevalence of anemia.

It has previously been shown in several animal experiments that platelet GPVI (glycoprotein VI) contributes to thrombosis, particularly in ischemic stroke. Moreover, GPVI levels are upregulated in stroke patients. This review describes the therapeutic roles of anti-GPVI antibody in preclinical models of ischemic stroke and provides the current evidence for potential benefits of glenzocimab, a Fab fragment of humanized anti-GPVI monoclonal antibody, in stroke patients. Anti-GPVI antibody, JAQ1, significantly decreased infarct volume and improved neurological function in mice with transient middle cerebral artery occlusion, a model of ischemic stroke, with no or minor bleeding tendency. Intravenous injection of glenzocimab in nonhuman primates produced rapid inhibition of ex vivo platelet aggregation induced by collagen (a GPVI ligand). Complete platelet inhibition is observed at 30 minutes following administration without increasing the risk of bleeding. In humans, glenzocimab is well tolerated and produces dose-dependent antiplatelet activity. More importantly, glenzocimab (125–1000 mg) was safe when administered as soon as possible (<3 hours) following reperfusion with the r-tPA (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke. Although glenzocimab 1000 mg (a selected dose) did not demonstrate a significant improvement in overall clinical outcomes, it appeared to provide benefits in severe cases and in patients who required thrombectomy. This promising efficacy together with a good safety profile of glenzocimab warrant further investigation in phase III (ACTISAVE [Adaptive Efficacy and Safety Study of Glenzocimab Used as an Add-On Therapy on Top of Standard of Care in the 4.5 Hours Following an Acute Ischemic Stroke]) clinical study.