Search

Background: Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes., Methods and Results: A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as <40% reduction in LDL-C. We externally validated the model in a Hong Kong (HK) cohort (n = 170,904). Patients were stratified into four groups by predicted SR and 10-year CVD risk score: [SR1] optimal SR & low risk; [SR2] sub-optimal SR & low risk; [SR3] optimal SR & high risk; [SR4] sub-optimal SR & high risk; and 10-year hazard ratios (HR) determined for first major adverse cardiovascular event (MACE). Our SR model included 12 characteristics, with an area under the curve of 0.70 (95% confidence interval [CI] 0.70-0.71; UK) and 0.68 (95% CI 0.67-0.68; HK). HRs for MACE in predicted sub-optimal SR with low CVD risk groups (SR2 to SR1) were 1.39 (95% CI 1.35-1.43, p<0.001; UK) and 1.14 (95% CI 1.11-1.17, p<0.001; HK). In both cohorts, patients with predicted sub-optimal SR with high CVD risk (SR4 to SR3) had elevated risk of MACE (UK HR 1.36, 95% CI 1.32-1.40, p<0.001: HK HR 1.25, 95% CI 1.21-1.28, p<0.001)., Conclusions: Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment., Competing Interests: NQ is a member of the most recent NICE Familial Hypercholesterolaemia & Lipid Modification Guideline Development Groups (CG71 & CG181). SW, IW are members of the Clinical Practice Research Datalink (CPRD) Independent Scientific Advisory Committee (ISAC). RKA currently holds an NIHR-SPCR funded studentship (2018-2021). SW reports honorarium from AMGEN and is also an employee of Janssen. KM holds the CW Malpethorpe Fellowship Award and reports personal fees from IQVIA Ltd have been received outside the submitted work. JB is supported by the Hong Kong Research Grants Council as a recipient of the Hong Kong PhD Fellowship Scheme. EC and IW report grants from Amgen. The remaining authors have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: A high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance., Methods: We performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1-4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results., Results: The mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction., Conclusion: Cardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction., Competing Interests: The authors have no real or perceived conflict of interest related to this work.

Objective: To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates., Methods: Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic., Results: We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty)., Conclusions: The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate., Competing Interests: The authors have read the journal’s policy and have the following competing interests: EWC has received honorarium from the Hospital Authority, research grants from Research Grants Council (RGC, HKSAR), Research Fund Secretariat of the Food and Health Bureau (HMRF, HKSAR), National Natural Science Fund of China, National Health and Medical research Council NHMRC, Australia), Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. ICKW has received research grants from Research Grants Council (RGC, Hong Kong), Innovative Medicines Initiative (IMI), Shire, Janssen-Cilag, Eli-Lily, Pfizer, Bayer, Amgen, and grants from European Union FP7 program, outside the submitted work. GKYT is an employee of Pfizer Upjohn Hong Kong Limited. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. The other authors have no competing interests to declare.

Objectives: We aimed to describe patterns in the usage of antivirals to treat influenza virus infection in hospitals in Hong Kong from 2000 through 2015., Methods: We analyzed centralized electronic health records that included dispensation information and diagnosis codes. Information collected on admissions included patient age, sex, admission year and month, and medications dispensed, and were matched with the first 15 discharge diagnosis codes. We divided monthly admission episodes by relevant population denominators to obtain admission rates, and stratified analyses by drug type, age group, and diagnosis codes., Results: Amantadine was used for influenza treatment in the early 2000s but changed with recommendations to avoid its use in 2006, and is now mainly used to treat Parkinson's disease. Oseltamivir usage increased substantially in 2009 and is now commonly used, with almost 40,000 hospitalizations treated with oseltamivir in the years 2012 through 2015, 66% of which was in persons ≥65 years of age. During the entire study period, of the 98,253 admission episodes in which oseltamivir was dispensed, 40,698 (41%) included a diagnosis code for influenza, and 80,283 (82%) included any diagnosis code for respiratory illness., Conclusions: The amount of oseltamivir used from 2012-15 was comparable to a separate ecological estimate of around 13,000 influenza-associated hospitalizations per year on average. We did not have access to individual patient laboratory testing data.

Objectives: Many of the cost-effectiveness analyses of apixaban against warfarin focused on Western populations but Asian evidence remains less clear. The present study aims to evaluate the cost-effectiveness of apixaban against warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) from a public institutional perspective in Hong Kong., Methods: We used a Markov model incorporating 12 health state transitions, and simulated the disease progression of NVAF in 1,000 hypothetical patients treated with apixaban/warfarin. Risks of clinical events were based on the ARISTOTLE trial and were adjusted with local International Normalized Ratio control, defined as the time in therapeutic range. Real-life input for the model, including patients' demographics and clinical profiles, post-event treatment patterns, and healthcare costs, were determined by a retrospective cohort of 40,569 incident patients retrieved from a Hong Kong-wide electronic medical database. Main outcome measurements included numbers of thromboembolic and bleeding events, life years, quality-adjusted life years (QALYs) and direct healthcare cost. When comparing apixaban and warfarin, treatment with incremental cost-effectiveness ratio (ICER) less than one local GDP per capita (USD 33,534 in 2014) was defined to be cost-effective., Results: In the lifetime simulation, fewer numbers of events were estimated for the apixaban group, resulting in reduced event-related direct medical costs. The estimated ICER of apixaban was USD 7,057 per QALY at base-case analysis and ranged from USD 1,061 to 14,867 per QALY under the 116 tested scenarios in deterministic sensitivity analysis. While in probabilistic sensitivity analysis, the probability of apixaban being the cost-effective alternative to warfarin was 96% and 98% at a willingness to pay threshold of USD 33,534 and 100,602 per QALY, respectively., Conclusions: Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong.

Background: The efficacy and safety of warfarin therapy for stroke prevention in atrial fibrillation (AF) depends on the time in therapeutic range (TTR). We aimed to assess the predictive ability of SAMe-TT2R2 score in Chinese AF patients on warfarin, whose TTR is notoriously poor., Methods and Results: This is a single-centre retrospective study. Patients with non-valvular AF on warfarin diagnosed between 1997 and 2011 were stratified according to SAMe-TT2R2 score, and TTR was calculated using Rosendaal method. The predictive power of SAMe-TT2R2 scores for good TTR i.e. >70% was assessed. We included 1,428 Chinese patients (mean age 76.2±8.7 years, 47.5% male) with non-valvular AF on warfarin. The mean and median TTR were 38.2±24.4% and 38.8% (interquartile range: 17.9% and 56.2%) respectively. TTR decreased progressively with increasing SAMe-TT2R2 score (p = 0.016). When the cut-off value of SAMe-TT2R2 score was set to 2, the sensitivity and specificity to predict TTR<70% were 85.7% and 17.8%, respectively. The corresponding positive and negative predictive values were 10.1% and 92.0%. After a mean follow-up of 4.7±3.6 years, 338 patients developed an ischemic stroke (4.96%/year). Patients with TTR≥70% had a lower annual risk of ischemic stroke of 3.67%/year compared with than those with TTR<70% (5.13%/year)(p = 0.08). Patients with SAMe-TT2R2 score ≤2 had the lowest risk of annual risk of ischemic stroke (3.49%/year) compared with those with SAMe-TT2R2 score = 3 (4.56%/year), and those with SAMe-TT2R2 score ≥4 (6.41%/year) (p<0.001). There was also a non-significant trend towards more intracranial hemorrhage with increasing SAMe-TT2R2 score., Conclusions: The SAMe-TT2R2 score correlates well with TTR in Chinese AF patients, with a score >2 having high sensitivity and negative predictive values for poor TTR. Ischemic stroke risk increased progressively with increasing SAMe-TT2R2 score, consistent with poorer TTRs at high SAMe-TT2R2 scores.

Active migration in both healthy and malignant cells requires the integration of information derived from soluble signaling molecules with positional information gained from interactions with the extracellular matrix and with other cells. How a cell responds and moves involves complex signaling cascades that guide the directional functions of the cytoskeleton as well as the synthesis and release of proteases that facilitate movement through tissues. The biochemical events of the signaling cascades occur in a spatially and temporally coordinated manner then dynamically shape the cytoskeleton in specific subcellular regions. Therefore, cell migration and invasion involve a precise but constantly changing subcellular nano-architecture. A multidisciplinary effort that combines new surface chemistry and cell biological tools is required to understand the reorganization of cytoskeleton triggered by complex signaling during migration. Here we generate a class of model substrates that modulate the dynamic environment for a variety of cell adhesion and migration experiments. In particular, we use these dynamic substrates to probe in real-time how the interplay between the population of cells, the initial pattern geometry, ligand density, ligand affinity and integrin composition affects cell migration and growth. Whole genome microarray analysis indicates that several classes of genes ranging from signal transduction to cytoskeletal reorganization are differentially regulated depending on the nature of the surface conditions.

Background: Dabigatran, an oral direct thrombin inhibitor, possesses several advantages over warfarin that can in principle simplify the management of stroke prevention in atrial fibrillation (AF). Nonetheless it remains unclear whether these advantages can translate to clinical practice and encourage long-term therapy. The objective was to describe long-term dabigatran therapy for stroke prevention in AF and to identify risk factors for discontinuation of therapy., Methods and Results: We studied 467 consecutive Chinese patients (72 ± 11 years, male: 53.8%) with a mean CHA2DS2-VASc score of 3.6 prescribed dabigatran for stroke prevention in AF from March 2010 to September 2013. Over a mean follow-up of 16 months, 101 patients (21.6%) permanently discontinued dabigatran. The mean time-to-discontinuation was 8 months. The most common reason for discontinuation was dyspepsia (30.7%), followed by other adverse events (17.8%) such as minor bleeding (8.9%), major gastrointestinal bleeding (7.9%), and intracranial hemorrhage (1%). Other reasons included dosing frequency (5.9%), fear of side effects (4.0%), lack of laboratory monitoring (1.0%), and cost (1.0%). Multivariable analysis revealed that low baseline estimated glomerular filtration rate (p = 0.02), absence of hypertension (p = 0.01), and prior use of a proton-pump inhibitor (p = 0.02) and H2-receptor blocker (p = 0.01) were independent predictors of drug discontinuation. In addition, there were altogether 9 ischemic strokes (1.5%/years), 3 intracranial hemorrhages (0.5%/year), and 24 major gastrointestinal bleedings (4.1%/year)., Conclusion: Dabigatran discontinuation is very common amongst Chinese AF patients. This reveals a management gap in the prevention of stroke in AF.