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1.
PLoS One ; 19(2): e0298036, 2024.
Article in English | MEDLINE | ID: mdl-38358964

ABSTRACT

BACKGROUND: Traditional risk assessment tools often lack accuracy when predicting the short- and long-term mortality following a non-ST-segment elevation myocardial infarction (NSTEMI) or Unstable Angina (UA) in specific population. OBJECTIVE: To employ machine learning (ML) and stacked ensemble learning (EL) methods in predicting short- and long-term mortality in Asian patients diagnosed with NSTEMI/UA and to identify the associated features, subsequently evaluating these findings against established risk scores. METHODS: We analyzed data from the National Cardiovascular Disease Database for Malaysia (2006-2019), representing a diverse NSTEMI/UA Asian cohort. Algorithm development utilized in-hospital records of 9,518 patients, 30-day data from 7,133 patients, and 1-year data from 7,031 patients. This study utilized 39 features, including demographic, cardiovascular risk, medication, and clinical features. In the development of the stacked EL model, four base learner algorithms were employed: eXtreme Gradient Boosting (XGB), Support Vector Machine (SVM), Naive Bayes (NB), and Random Forest (RF), with the Generalized Linear Model (GLM) serving as the meta learner. Significant features were chosen and ranked using ML feature importance with backward elimination. The predictive performance of the algorithms was assessed using the area under the curve (AUC) as a metric. Validation of the algorithms was conducted against the TIMI for NSTEMI/UA using a separate validation dataset, and the net reclassification index (NRI) was subsequently determined. RESULTS: Using both complete and reduced features, the algorithm performance achieved an AUC ranging from 0.73 to 0.89. The top-performing ML algorithm consistently surpassed the TIMI risk score for in-hospital, 30-day, and 1-year predictions (with AUC values of 0.88, 0.88, and 0.81, respectively, all p < 0.001), while the TIMI scores registered significantly lower at 0.55, 0.54, and 0.61. This suggests the TIMI score tends to underestimate patient mortality risk. The net reclassification index (NRI) of the best ML algorithm for NSTEMI/UA patients across these periods yielded an NRI between 40-60% (p < 0.001) relative to the TIMI NSTEMI/UA risk score. Key features identified for both short- and long-term mortality included age, Killip class, heart rate, and Low-Molecular-Weight Heparin (LMWH) administration. CONCLUSIONS: In a broad multi-ethnic population, ML approaches outperformed conventional TIMI scoring in classifying patients with NSTEMI and UA. ML allows for the precise identification of unique characteristics within individual Asian populations, improving the accuracy of mortality predictions. Continuous development, testing, and validation of these ML algorithms holds the promise of enhanced risk stratification, thereby revolutionizing future management strategies and patient outcomes.


Subject(s)
Non-ST Elevated Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Non-ST Elevated Myocardial Infarction/diagnosis , Heparin, Low-Molecular-Weight , Data Science , Bayes Theorem , Angina, Unstable , Risk Assessment , Arrhythmias, Cardiac
2.
Hypertens Res ; 47(2): 352-357, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37673957

ABSTRACT

Resistant hypertension is a well-recognised clinical challenge. However, the definition and epidemiology of true resistant hypertension (RH) are less understood, especially in Asia. This cross-sectional study examined the prevalence of RH referred from primary care clinics based on various guidelines. RH was defined as blood pressure (BP) being above the threshold using ambulatory blood pressure monitoring despite adequate lifestyle measures and optimal treatment with ≥3 medications at maximally tolerated doses. Between one in four (n = 94, 24.0% using Malaysian guidelines) and up to two-thirds (n = 249, 63.7% using 2018 American guidelines) of adults referred for uncontrolled hypertension met the criteria of true RH. Of those with RH, a further one-quarter (n = 26, 26.6%) were deemed to have refractory hypertension (elevated BP despite treatment with at least 5 antihypertensive medications). Adults with RH were generally younger, more likely to be male, had a higher BMI and were more likely to have gout, CKD, and angina compared to those with controlled hypertension. The prevalence of RH amongst Asian adults with poor hypertension control is high. A concerted effort is needed to reduce the high burden of RH, especially among this population.


Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Adult , Male , Humans , United States , Female , Prevalence , Malaysia/epidemiology , Cross-Sectional Studies , Hypertension/drug therapy , Hypertension/epidemiology , Blood Pressure/physiology , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Risk Factors
3.
Clin Case Rep ; 11(6): e7580, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37351358

ABSTRACT

Key Clinical Message: The high-risk "Shark Fin" electrocardiogram (ECG) pattern has been associated with transmural ischemia but can also result from electrolyte anomalies. Therefore, the decision for invasive coronary catheterization requires a detailed history and dedicated biochemical tests. Abstract: Pseudo-infarction ECG pattern resembling "Shark Fin" was demonstrated in a 76-year-old lady with a previous total thyroidectomy who presented with unspecific symptoms. An incidental finding of hypokalemia and hypocalcemia was thought to be related to delayed onset hypoparathyroidism. Potential etiologies like coronary vasospasm and catecholamine-associated myocardial injury were suggested.

4.
Pharmaceuticals (Basel) ; 15(6)2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35745638

ABSTRACT

Acute myocardial infarction (AMI) is associated with heightened thrombin generation. There are limited data relating to thrombin generation and left ventricular (LV) scarring and LV dilatation in post-MI LV remodeling. We studied 113 patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (PPCI) (n = 76) or pharmaco-invasive management (thrombolysis followed by early PCI, n = 37). Endogenous thrombin potential (ETP) was measured at baseline, 1 month and 6 months. Cardiovascular magnetic resonance imaging was performed at baseline and 6 months post-MI. Outcomes studied were an increase in scar change, which was defined as an increase in left ventricular infarct size of any magnitude detected by late gadolinium enhancement, adverse LV remodeling, defined as dilatation (increase) of left ventricular end-diastolic volume (LVEDV) by more than 20% and an increase in left ventricular ejection fraction (LVEF). The mean age was 55.19 ± 8.25 years and 91.2% were men. The baseline ETP was similar in the PPCI and pharmaco-invasive groups (1400.3 nM.min vs. 1334.1 nM.min, p = 0.473). Each 10-unit increase in baseline ETP was associated with a larger scar size (adjusted OR 1.020, 95% CI 1.002-1.037, p = 0.027). Baseline ETP was not associated with adverse LV remodeling or an increase in LVEF. There was no difference in scar size or adverse LV remodeling among patients undergoing PPCI vs. pharmaco-invasive management or patients receiving ticagrelor vs. clopidogrel. Enhanced thrombin generation after STEMI is associated with a subsequent increase in myocardial scarring but not LV dilatation or an increase in LVEF at 6 months post-MI.

5.
Hypertens Res ; 45(7): 1111-1122, 2022 07.
Article in English | MEDLINE | ID: mdl-35650248

ABSTRACT

Hypertension is highly prevalent and a major contributor to cardiovascular mortality and morbidity. In spite of the availability of efficacious, safe and affordable anti-hypertensive drugs, hypertension remains poorly controlled in the majority of hypertensive patients. Various reasons including non-adherence to the anti-hypertensive drugs, account for the poor control. Resistant hypertension is also one of the reasons for poor control of blood pressure (BP). The sympathetic nervous system (SNS) has long been recognized as one of the determinants in the pathophysiology of a raised BP. Overactivity of the SNS is a contributor to sustained arterial hypertension. Renal denervation (RDN) is increasingly recognized as a safe and effective adjunctive therapy to control BP with or without pharmacotherapy. Hence for patients who remain uncontrolled despite all efforts, renal denervation (RDN) is a novel treatment that can potentially improve BP control, hence reducing the major adverse cardiovascular events (MACE). More recent randomized, sham control trials of RDN have shown that RDN produces a sustained lowering of BP. To date, this lowering of BP through RDN is maintained for at least 3 years. Furthermore, this procedure has been found to be safe. Hence this consensus summarises the science behind RDN and the available clinical data to support the use of this therapy. It is hoped that this consensus will offer guidance on the importance of identifying patients who will benefit most from this therapy. A multidisciplinary team approach in the management of the patient undergoing RDN is recommended.


Subject(s)
Antihypertensive Agents , Hypertension , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Pressure , Denervation/methods , Humans , Hypertension/drug therapy , Hypertension/surgery , Kidney , Sympathectomy/methods , Treatment Outcome
6.
JMIR Res Protoc ; 11(2): e31885, 2022 Feb 10.
Article in English | MEDLINE | ID: mdl-35142634

ABSTRACT

BACKGROUND: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.

7.
Eur Cardiol ; 16: e43, 2021 Feb.
Article in English | MEDLINE | ID: mdl-34815751

ABSTRACT

Advanced age, diabetes, and chronic kidney disease not only increase the risk for ischaemic events in chronic coronary syndromes (CCS) but also confer a high bleeding risk during antiplatelet therapy. These special populations may warrant modification of therapy, especially among Asians, who have displayed characteristics that are clinically distinct from Western patients. Previous guidance has been provided regarding the classification of high-risk CCS and the use of newer-generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) after acute coronary syndromes (ACS) in Asia. The authors summarise evidence on the use of these P2Y12 inhibitors during the transition from ACS to CCS and among special populations. Specifically, they present recommendations on the roles of standard dual antiplatelet therapy, shortened dual antiplatelet therapy and single antiplatelet therapy among patients with coronary artery disease, who are either transitioning from ACS to CCS; elderly; or with chronic kidney disease, diabetes, multivessel coronary artery disease and bleeding events during therapy.

8.
Europace ; 23(7): 1016-1023, 2021 07 18.
Article in English | MEDLINE | ID: mdl-33782701

ABSTRACT

AIMS: Atrial fibrillation (AF) is a preventable cause of ischaemic stroke but it is often undiagnosed and undertreated. The utility of smartphone electrocardiogram (ECG) for the detection of AF after ischaemic stroke is unknown. The aim of this study is to determine the diagnostic yield of 30-day smartphone ECG recording compared with 24-h Holter monitoring for detecting AF ≥30 s. METHODS AND RESULTS: In this multicentre, open-label study, we randomly assigned 203 participants to undergo one additional 24-h Holter monitoring (control group, n = 98) vs. 30-day smartphone ECG monitoring (intervention group, n = 105) using KardiaMobile (AliveCor®, Mountain View, CA, USA). Major inclusion criteria included age ≥55 years old, without known AF, and ischaemic stroke or transient ischaemic attack (TIA) within the preceding 12 months. Baseline characteristics were similar between the two groups. The index event was ischaemic stroke in 88.5% in the intervention group and 88.8% in the control group (P = 0.852). AF lasting ≥30 s was detected in 10 of 105 patients in the intervention group and 2 of 98 patients in the control group (9.5% vs. 2.0%; absolute difference 7.5%; P = 0.024). The number needed to screen to detect one AF was 13. After the 30-day smartphone monitoring, there was a significantly higher proportion of patients on oral anticoagulation therapy at 3 months compared with baseline in the intervention group (9.5% vs. 0%, P = 0.002). CONCLUSIONS: Among patients ≥55 years of age with a recent cryptogenic stroke or TIA, 30-day smartphone ECG recording significantly improved the detection of AF when compared with the standard repeat 24-h Holter monitoring.


Subject(s)
Atrial Fibrillation , Brain Ischemia , Ischemic Attack, Transient , Stroke , Atrial Fibrillation/diagnosis , Brain Ischemia/diagnosis , Electrocardiography , Electrocardiography, Ambulatory , Humans , Ischemic Attack, Transient/diagnosis , Middle Aged , Smartphone , Stroke/diagnosis
9.
PLoS One ; 16(2): e0246474, 2021.
Article in English | MEDLINE | ID: mdl-33556136

ABSTRACT

BACKGROUND: Sex and gender differences in acute coronary syndrome (ACS) have been well studied in the western population. However, limited studies have examined the trends of these differences in a multi-ethnic Asian population. OBJECTIVES: To study the trends in sex and gender differences in ACS using the Malaysian NCVD-ACS Registry. METHODS: Data from 24 hospitals involving 35,232 ACS patients (79.44% men and 20.56% women) from 1st. Jan 2012 to 31st. Dec 2016 were analysed. Data were collected on demographic characteristics, coronary risk factors, anthropometrics, treatments and outcomes. Analyses were done for ACS as a whole and separately for ST-segment elevation myocardial infarction (STEMI), Non-STEMI and unstable angina. These were then compared to published data from March 2006 to February 2010 which included 13,591 ACS patients (75.8% men and 24.2% women). RESULTS: Women were older and more likely to have diabetes mellitus, hypertension, dyslipidemia, previous heart failure and renal failure than men. Women remained less likely to receive aspirin, beta-blocker, angiotensin-converting enzyme inhibitor (ACE-I) and statin. Women were less likely to undergo angiography and percutaneous coronary intervention (PCI) despite an overall increase. In the STEMI cohort, despite a marked increase in presentation with Killip class IV, women were less likely to received primary PCI or fibrinolysis and had longer median door-to-needle and door-to-balloon time compared to men, although these had improved. Women had higher unadjusted in-hospital, 30-Day and 1-year mortality rates compared to men for the STEMI and NSTEMI cohorts. After multivariate adjustments, 1-year mortality remained significantly higher for women with STEMI (adjusted OR: 1.31 (1.09-1.57), p<0.003) but were no longer significant for NSTEMI cohort. CONCLUSION: Women continued to have longer system delays, receive less aggressive pharmacotherapies and invasive treatments with poorer outcome. There is an urgent need for increased effort from all stakeholders if we are to narrow this gap.


Subject(s)
Acute Coronary Syndrome/epidemiology , Cardiovascular Diseases/epidemiology , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Asian People , Aspirin/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/therapy , Data Management , Databases, Factual , Female , Fibrinolysis , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Prospective Studies , Registries/statistics & numerical data , Sex Factors , Treatment Outcome
10.
Eur Heart J Qual Care Clin Outcomes ; 7(1): 6-17, 2021 01 25.
Article in English | MEDLINE | ID: mdl-32584986

ABSTRACT

The aim of this study is to gain insight into the differences in demographics of ST-elevation myocardial infarction (STEMI) patients in Asia-Pacific, as well as inter-country variation in treatment and mortality outcomes. Systematic review of published studies and reports from known registries in Australia, Japan, Korea, Singapore, and Malaysia that began data collection after the year 2000. Supplementary self-report survey questionnaire on public health data answered by representative cardiologists working in these countries. Twenty studies comprising of 158 420 patients were included in the meta-analysis. The mean age was 61.6 years. Chronic kidney disease prevalence was higher in Japan, while dyslipidaemia was low in Korea. Use of aspirin, P2Y12 inhibitors, and statins were high throughout, but ACEi/ARB and ß-blocker prescriptions were lower in Japan and Malaysia. Reperfusion strategies varied greatly, with high rates of primary percutaneous coronary intervention (pPCI) in Korea (91.6%), whilst Malaysia relies far more on fibrinolysis (72.6%) than pPCI (9.6%). Similarly, mortality differed, with 1-year mortality from STEMI was considerably greater in Malaysia (17.9%) and Singapore (11.2%) than in Korea (8.1%), Australia (7.8%), and Japan (6.2%). The countries were broadly similar in development and public health indices. Singapore has the highest gross national income and total healthcare expenditure per capita, whilst Malaysia has the lowest. Primary PCI is available in all countries 24/7/365. Despite broadly comparable public health systems, differences exist in patient profile, in-hospital treatment, and mortality outcomes in these five countries. Our study reveals areas for improvements. The authors advocate further registry-based multi-country comparative studies focused on the Asia-Pacific region.


Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Asia/epidemiology , Demography , Humans , Middle Aged , ST Elevation Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/therapy
11.
Hosp Pract (1995) ; 49(2): 110-118, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33249880

ABSTRACT

Sarawak General Hospital, which is the only public access tertiary referral center in Sarawak State for all clinical specialties, was designated a hybrid hospital to treat both COVID-19 and non-COVID-19 patients. During the initial surge of patients admitted with COVID-19, there was also a corresponding increase in health-care workers (HCWs) detected with COVID-19 infection. The latter being isolated, and the large number of staff members that had come into contact with COVID-19 being quarantined from work, placed further strain on the health-care services. The staff mass screening strategy was a policy decision made by the hospital in response to infection among HCWs, and it aimed to reduce in-hospital transmission (particularly among asymptomatic staff), mitigate workforce depletion due to quarantining, and protect the health-care workforce. In this study, we assessed the detection rate of COVID-19 infection from staff mass testing over a five-week period, and described our experience of adopting this surveillance screening strategy alongside ongoing contact tracing and symptomatic screening strategies. Although it was thought that such periodic staff surveillance might be helpful in protecting the health-care workforce within a short period, the long-term implications, especially in settings with limited resources, is significant and therefore explored in this paper. Our findings might provide an evidence-based reference for the future planning of an optimal strategy with the least compromise in care for a larger proportion of non-COVID-19 patients amid efforts against COVID-19 in a large non-COVID-designated hospital with hybrid status.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Health Personnel , Mass Screening/organization & administration , Tertiary Care Centers/organization & administration , Cross Infection/prevention & control , Humans , Infection Control/organization & administration , Longitudinal Studies , Malaysia , Personal Protective Equipment/statistics & numerical data , Practice Guidelines as Topic , SARS-CoV-2
12.
BMC Cardiovasc Disord ; 20(1): 511, 2020 12 07.
Article in English | MEDLINE | ID: mdl-33287705

ABSTRACT

BACKGROUND: Data on clinical characteristics of acute decompensated heart failure (ADHF) in Malaysia especially in East Malaysia is lacking. METHODS: This is a prospective observational study in Sarawak General Hospital, Medical Department, from October 2017 to September 2018. Patients with primary admission diagnosis of ADHF were recruited and followed up for 90 days. Data on patient's characteristics, precipitating factors, medications and short-term clinical outcomes were recorded. RESULTS: Majority of the patients were classified in lower socioeconomic group and the mean age was 59 years old. Hypertension, diabetes mellitus and dyslipidaemia were the common underlying comorbidities. Heart failure with ischemic aetiology was the commonest ADHF admission precipitating factor. 48.6% of patients were having preserved ejection fraction HF and the median NT-ProBNP level was 4230 pg/mL. Prescription rate of the evidence-based heart failure medication was low. The in-patient mortality and the average length of hospital stay were 7.5% and 5 days respectively. 43% of patients required either ICU care or advanced cardiopulmonary support. The 30-day, 90-day mortality and readmission rate were 13.1%, 11.2%, 16.8% and 14% respectively. CONCLUSION: Comparing with the HF data from West and Asia Pacific, the short-term mortality and readmission rate were high among the ADHF patients in our study cohort. Maladaptation to evidence-based HF prescription and the higher prevalence of cardiovascular risk factors in younger patients were among the possible issues to be addressed to improve the HF outcome in regions with similar socioeconomic background.


Subject(s)
Heart Failure , Acute Disease , Aged , Cardiovascular Agents/therapeutic use , Female , Heart Disease Risk Factors , Heart Failure/diagnosis , Heart Failure/drug therapy , Heart Failure/mortality , Heart Failure/physiopathology , Hospitalization , Hospitals, General , Humans , Malaysia , Male , Middle Aged , Prevalence , Prognosis , Prospective Studies , Risk Assessment , Tertiary Care Centers , Time Factors
13.
Clin Appl Thromb Hemost ; 26: 1076029620972473, 2020.
Article in English | MEDLINE | ID: mdl-33284050

ABSTRACT

Routine coagulation tests do not enable rapid, accurate determination of direct oral anticoagulant (DOAC) therapy. The ecarin clotting assay (ECA), performed on the ClotPro viscoelastic testing device, may enable sensitive and specific detection of dabigatran. We assessed the association between trough plasma dabigatran concentration and clotting time (CT) in the ClotPro ECA, in patients with non-valvular atrial fibrillation (NVAF). Each patient provided a single venous blood sample, ∼1 hour before dabigatran dosing. The study included 118 patients, of whom 64 were receiving dabigatran 110 mg twice daily and 54 were receiving 150 mg twice daily. ECA CT was moderately correlated with trough plasma dabigatran concentration (r = 0.80, p < 0.001). Slight trends toward increased plasma dabigatran concentration and prolonged ECA CT were apparent with 150 mg versus the 110 mg dose (differences not statistically significant). Individuals with creatinine clearance below 50 mL/minute had significantly higher plasma dabigatran concentrations and significantly prolonged ECA CT versus those with creatinine clearance ≥50 mL/minute. In conclusion, this preliminary study has demonstrated that CT in the ClotPro ECA reflects the plasma concentration of dabigatran in patients with NVAF. The ECA could potentially be used to assess the impact of dabigatran on a patient's coagulation status.


Subject(s)
Antithrombins/therapeutic use , Atrial Fibrillation/drug therapy , Blood Coagulation/drug effects , Dabigatran/therapeutic use , Aged , Antithrombins/blood , Antithrombins/pharmacology , Atrial Fibrillation/blood , Blood Coagulation Tests , Dabigatran/blood , Dabigatran/pharmacology , Female , Humans , Male , Middle Aged , Preliminary Data , Prospective Studies
14.
Expert Opin Drug Metab Toxicol ; 16(9): 837-851, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32729743

ABSTRACT

INTRODUCTION: Statins have been established as the standard of care for dyslipidemia and preventing cardiovascular diseases while posing few safety concerns. However, misconceptions about statin intolerance lead to their underuse, indicating a need to improve the understanding of the safety of this treatment. AREAS COVERED: We searched PubMed and reviewed literatures related to statin intolerance published between February 2015 and February 2020. Important large-scale or landmark studies published before 2015 were also cited as key evidence. EXPERT OPINION: Optimal lowering of low-density lipoprotein cholesterol with statins substantially reduces the risk of cardiovascular events. Muscle adverse events (AEs) were the most frequently reported AEs by statin users in clinical practice, but they usually occurred at a similar rate with statins and placebo in randomized controlled trials and had a spurious causal relationship with statin treatment. We proposed a rigorous definition for identifying true statin intolerance and present the criteria for defining different forms of muscle AEs and an algorithm for their management. True statin intolerance is uncommon, and every effort should be made to exclude false statin intolerance and ensure optimal use of statins. For the management of statin intolerance, statin-based approaches should be prioritized over non-statin approaches.


Subject(s)
Dyslipidemias/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Muscular Diseases/chemically induced , Algorithms , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cholesterol, LDL/blood , Dyslipidemias/complications , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Muscular Diseases/diagnosis
15.
Glob Heart ; 13(4): 241-244, 2018 12.
Article in English | MEDLINE | ID: mdl-30213574

ABSTRACT

BACKGROUND: Warfarin is an anticoagulant indicated for patients who had undergone mechanical heart valve(s) replacement (MHVR). In these patients, time in therapeutic range (TTR) is important in predicting the bleeding and thrombotic risks. OBJECTIVE: This study aimed to describe the anticoagulation control of warfarin using TTR in patients with MHVR in a tertiary health care referral Center. METHODS: Data were collected retrospectively by reviewing clinical notes of outpatients who attended international normalized ratio (INR) clinics in November 2015. Patients who had MHVR and who took warfarin were included. The data collected were demographics, relevant laboratory investigations, and patients' prior medical history. TTR was calculated using Rosendaal and traditional methods. RESULTS: A total of 103 patients with MHVR were recruited. The mean age was 51.72 ± 13.97 years and 46.6% were male. A total of 54.4% had mitral valve replacement (MVR), whereas 26.2% had aortic valve replacement (AVR). The mean TTR calculated using the Rosendaal method was 57.1%. There was no significant difference among patients with AVR, MVR, and both valves (AMVR) in terms of TTR (AVR vs. MVR vs. AMVR, 62.94 ± 23.08, 54.12 ± 21.62, 57.63 ± 17.47; p = 0.213). The average dose of warfarin for all groups was approximately 3 mg/day. Moreover, MVR, AVR, and AMVR patients who had TTR (Rosendaal method) ≤60% were 58.9%, 37.0%, and 45.0%, respectively. Only 4.8% had minor bleeding, whereas none had stroke in the period of TTR determination. CONCLUSIONS: Despite a majority of patients having <60% TTR, there were low incidences of bleeding and stroke events in this center. There were no factors found to be associated with INR control in this study.


Subject(s)
Heart Valve Prosthesis/adverse effects , Postoperative Complications/prevention & control , Thrombosis/prevention & control , Warfarin/administration & dosage , Anticoagulants/administration & dosage , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Incidence , Malaysia/epidemiology , Male , Middle Aged , Outpatients , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Thrombosis/epidemiology , Thrombosis/etiology , Time Factors
16.
Pharmacogenomics ; 19(15): 1151-1157, 2018 10.
Article in English | MEDLINE | ID: mdl-30191759

ABSTRACT

AIM: Recurrent thrombotic events still occur despite dual antiplatelet therapy in patient's post percutaneous coronary intervention (PCI) could be attributed to high on-treatment platelet reactivity. METHODS: A 44-year-old male, who had staged PCI to left anterior descending (LAD) 2 weeks after an anterior MI, with a drug-coated stent was readmitted with new anterior STEMI 35 days later. Coronary angiogram revealed mid-stent thrombus in situ. He had further uncomplicated PCI. Platelet function testing and genotyping showed clopidogrel high on-treatment platelet reactivity and CYP2C19*3/*17 genotype. Ticagrelor was commenced. RESULTS & CONCLUSION: This case study is the first reported in Malaysia to document a patient with a CYP2C19*3/*17 genotype presenting with a stent thrombosis after an uncomplicated index PCI procedure.


Subject(s)
Blood Platelets/drug effects , Clopidogrel/adverse effects , Cytochrome P-450 CYP2C19/genetics , Platelet Aggregation Inhibitors/adverse effects , Thrombosis/chemically induced , Thrombosis/genetics , Adult , Drug-Eluting Stents/adverse effects , Genotype , Humans , Male , Platelet Aggregation Inhibitors/therapeutic use , Ticagrelor/therapeutic use
17.
J Thromb Thrombolysis ; 46(4): 541-548, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30155672

ABSTRACT

The objectives of this study are to compare steady-state trough (Cmin,ss) and peak (Cmax,ss) concentrations of rivaroxaban between Asians and Caucasians and to evaluate the relationship between rivaroxaban concentrations and prothrombin time/international normalized ratio (PT/INR). Recruited patients were advised on the time to take rivaroxaban. Cmin,ss and PT/INR were taken when patients arrived. Cmax,ss and PT/INR were drawn between 2 and 4 h later after the patient took rivaroxaban with food. Thirty patients were included in the analyses: 57% (n = 17) males and 43% (n = 13) females, 77% (n = 23) on 20 mg and 23% (n = 7) on 15 mg. Median PTtrough and PTpeak are moderately correlated with Cmin,ss (r2 = 0.43) and Cmax,ss (r2 = 0.49), respectively. Patients on 15 mg have lower Cmin,ss and Cmax,ss versus Caucasians [12 ng/ml vs. 57 ng/ml (Cmin,ss); 87 ng/ml vs. 229 ng/ml (Cmax,ss), p < 0.01 for both]. Patients on 20 mg also have lower Cmin,ss and Cmax,ss versus Caucasians [14 ng/ml vs. 44 ng/ml (Cmin,ss); 101 ng/ml vs. 249 ng/ml (Cmax,ss), p < 0.01 for both]. Subgroup analysis shows patients with BMI ≥ 30 have lower Cmax,ss than patients with BMI < 30 [80.47 ng/ml vs. 124 (p = 0.014)]. Cmin,ss and Cmax,ss were lower in Singaporeans than Caucasians. This may have an impact on the effectiveness of rivaroxaban in Singaporeans. Patients with higher BMI may not benefit similarly as patients with lower BMI. Lastly, the Dade Innovin reagent's measure of PT/INR is not sensitive towards changes in rivaroxaban concentrations.


Subject(s)
Asian People , Blood Coagulation Tests , Rivaroxaban/blood , White People , Adult , Body Mass Index , Female , Humans , International Normalized Ratio , Male , Prothrombin Time
19.
JACC Basic Transl Sci ; 3(2): 163-175, 2018 Apr.
Article in English | MEDLINE | ID: mdl-30062203

ABSTRACT

We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI). Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature's 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature.

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