Displaying publications 41 - 60 of 90 in total

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  1. Ho KT, Chin KW, Ng KS, Alemao E, Rajagopalan S, Yin D
    Am J Cardiovasc Drugs, 2006;6(6):383-91.
    PMID: 17192128
    BACKGROUND: Cardiovascular disease remains a leading cause of death worldwide, with hypercholesterolemia being a major risk factor. Evidence-based consensus guidelines have recommended consideration of increasingly stringent cholesterol-lowering goals, yet most patients do not meet these targets. Coronary heart disease (CHD) event and mortality rates and mean serum cholesterol levels have declined in Singapore in recent years; however, certain groups remain at elevated risk.

    OBJECTIVE: To determine (i) proportions of patients with CHD in Singapore who achieved goals for serum low-density lipoprotein-cholesterol (LDL-C); and (ii) factors influencing goal attainment.

    METHODS: A historical cohort study was conducted using records from the Singapore Cardiac Databank, a national registry of CHD patients. Serum LDL-C goal attainment was assessed in 5174 survivors of acute myocardial infarction or coronary revascularization (i.e. coronary artery bypass graft surgery or percutaneous coronary interventions), of whom 3811 (73.7%) were at very high risk.

    RESULTS: At baseline, the mean patient age was 60.3 years, mean serum value of total cholesterol was 228 mg/dL, and mean LDL-C was 163 mg/dL. Of all CHD patients, approximately 70% did not achieve a serum LDL-C target of <100 mg/dL. Most patients receiving HMG-CoA reductase inhibitor (statin) regimens were treated initially with low- to medium-equipotency regimens and were never titrated to stronger regimens. The vast majority (approximately 94%) of patients at very high risk did not achieve the stringent serum LDL-C target of <70 mg/dL. Patients receiving higher potency statins were significantly more likely to achieve LDL-C goals, whereas those with higher baseline LDL-C levels or Malaysian ethnicity were less likely to achieve LDL-C goals.

    CONCLUSIONS: Most CHD patients in the large group of Singapore residents with CHD in the present study did not achieve recommended LDL-C targets. A more effective disease-management approach, including patient education concerning lifestyle modification (e.g. diet, physical activity), efforts to enhance medication adherence, and more effective, well tolerated therapies such as high-equipotency or high-dose statins and statin combination regimens, may be needed to improve achievement of consensus cholesterol targets. This is the first study of cholesterol goal attainment in a large group of Southeast Asians and serves as a baseline for future evaluations in Asian populations.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
  2. Bosch J, Lonn EM, Dagenais GR, Gao P, Lopez-Jaramillo P, Zhu J, et al.
    Stroke, 2021 08;52(8):2494-2501.
    PMID: 33985364 DOI: 10.1161/STROKEAHA.120.030790
    Background and Purpose: The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups.

    Methods: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.

    Results: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59–1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55–1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34–1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41–2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52–0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37–0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36–0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23–0.72]).

    Conclusions: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

    Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00468923.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage*
  3. Seng CK, Abdullah N, Aminudin N
    Int J Med Mushrooms, 2017;19(9):797-807.
    PMID: 29199554 DOI: 10.1615/IntJMedMushrooms.2017024374
    Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent. Among 5 extracts/fractions tested, the semipolar ethyl acetate (EA) fraction demonstrated good antioxidant capacity based on total phenolic content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous ion-chelating ability, cupric ion-reducing antioxidant capacity, and lipid peroxidation assays. The EA fraction also showed the strongest inhibitory effect on Cu2+-induced LDL oxidation via thiobarbituric acid reactive substances formation and HMG-CoA reductase activity. Chemical analysis conjointly identified 10 phenolic compounds (4 benzoic acid derivatives, 3 flavonoids, 1 cinnamic acid, 1 hexahydroxydiphenic acid dilactone, and 1 xanthone derivative), some of which play pivotal roles in arresting the physiopathogenesis of atherosclerosis, thereby attenuating the risk of cardiovascular events occurring.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology*
  4. Tan CE, Loh LM, Tai ES
    Singapore Med J, 2003 Dec;44(12):635-8.
    PMID: 14770258
    A substantial number of physicians in Asian countries believe that Asian patients need lower doses of statins to achieve therapeutic lipid target because of the smaller size of patients. This belief is deep rooted and we looked at the SGH Lipid Clinic to determine if our experience bears out this belief. Between 1996 and August 2000, the Lipid Unit treated a total of 841 patients, of which 548 patients (77.5% Chinese, 12.1% Malays, 7.6% Asian Indians; 49.6% males, 50.4% females; 54.7% diabetics, 45.3% non-diabetic) were on statins alone. These patients had > or =2 coronary risk factors, diabetes mellitus or documented coronary heart disease. The pre-treatment lipid levels or the worst lipid levels available were entered as the baseline lipid values (mean LDL-C: 5.38+1.5 mmol/l). Duration of therapy ranged from six months to five years. The choice and titration of statins were determined by attending physicians. The median statin dose (Simvastatin equivalent) was 20.0 mg with 52.5% requiring 20 mg or more. Statin dose did not differ between diabetic and non-diabetic subjects. The median statin dose was 15 mg for the lower two tertiles and 20 mg for the upper tertile; this difference did not achieve statistical significance. The reduction in LDL cholesterol was 41.5% (40.1-42.8) and total cholesterol was 33.0% (32.9-34.1). Only 25% of our patients achieved LDL cholesterol of less than 2.6 mmol/l whilst 77.5% had LDL cholesterol less than 3.4 mmol/l. Our experience at the Lipid Clinic suggests that the Asian patients require similar statin doses to achieve target cholesterol levels.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage*
  5. Ibrahim N', Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(13):1524-32.
    PMID: 23876090
    Fracture healing is a process of recovering injured bone tissue forms and functions. Osteoporosis can delay the healing process, which contributes to personal suffering and loss of activities. Osteoporosis patients tend to lose bone mass at the metaphyseal region which require treatment to increase bone mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in women which subsequently resulted in fractures even under slight trauma. Estrogen Replacement Therapy (ERT), the recommended therapy for postmenopausal osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and cardiovascular diseases. As osteoporotic fractures are becoming a public health issue, alternative treatment is now being thoroughly explored. The potential agent is statins, the HMG-CoA reductase inhibitor which is widely used for hypercholesterolemia treatment. Statins have been found to increase bone mass by stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular Endothelial Growth Factor (VEGF) production. However, these bone forming effects were achieved at very high systemic doses. Therefore, studies on locally applied statins are required to further explore the ability of statins to stimulate bone formation at acceptable doses for better fracture healing. This review highlights the animal and clinical studies on fracture healing promotions by statins and the mechanisms involved.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
  6. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Basic Clin Pharmacol Toxicol, 2012 Apr;110(4):370-7.
    PMID: 22023326 DOI: 10.1111/j.1742-7843.2011.00825.x
    There has been recent interest in combining antiplatelets, angiotensin-converting enzyme inhibitors (ACEIs) and statins in primary and secondary ischaemic stroke prevention. This observational study was performed to evaluate the impact of adding ACEIs and/or statins to antiplatelets on post-stroke in-hospital mortality. Ischaemic stroke patients attending a hospital in Malaysia over an 18-month period were evaluated. Patients were categorized according to their vital status at discharge. Data included demographic information, risk factors, clinical characteristics and previous medications with particular attention on antiplatelets, ACEIs and statins. In-hospital mortality was compared among patients who were not taking antiplatelets, ACEIs or statins before stroke onset versus those who were taking antiplatelets alone or in combination with either ACEIs, statins or both. Data analysis was performed using SPSS version 15. Overall, 637 patients met the study inclusion criteria. After controlling for the effects of confounders, adding ACEIs or statins to antiplatelets significantly decreased the incidence of death after stroke attack by 68% (p = 0.036) and 81% (p = 0.010), respectively, compared to patients on antiplatelets alone or none of these medications. Additionally, the addition of both ACEIs and statins to antiplatelet medication resulted in the highest reduction (by 94%) of the occurrence of death after stroke attack (p < 0.001). Our results suggest that adding ACEIs and/or statins to antiplatelets for patients at risk of developing stroke, either as a primary or as a secondary preventive regimen, was associated with a significant reduction in the incidence of mortality after ischaemic stroke than antiplatelets alone. These results might help reduce the rate of ischaemic stroke morbidity and mortality by enhancing the application of specific therapeutic and management strategies for patients at a high risk of acute stroke.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
  7. Amudha K, Choy AM, Mustafa MR, Lang CC
    Cardiovasc Ther, 2008;26(4):253-61.
    PMID: 19035876 DOI: 10.1111/j.1755-5922.2008.00064.x
    Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P = 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P = 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P = 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P = 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology*; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
  8. Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, et al.
    N Engl J Med, 2016 May 26;374(21):2032-43.
    PMID: 27039945 DOI: 10.1056/NEJMoa1600177
    BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
    METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
    RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
    CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
    Note: Malaysia is a study site (Author: Yusoff K)
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage*; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
  9. Leporowski A, Godman B, Kurdi A, MacBride-Stewart S, Ryan M, Hurding S, et al.
    Expert Rev Pharmacoecon Outcomes Res, 2018 Dec;18(6):655-666.
    PMID: 30014725 DOI: 10.1080/14737167.2018.1501558
    BACKGROUND: Prescribing of lipid-lowering agents (LLAs) has increased worldwide including in Scotland with increasing prevalence of coronary heart disease, and higher dose statins have been advocated in recent years. There have also been initiatives to encourage prescribing of generic versus patented statins to save costs without compromising care. There is a need to document these initiatives and outcomes to provide future direction.

    METHOD: Assessment of utilization (items dispensed) and expenditure of key LLAs (mainly statins) between 2001 and 2015 in Scotland alongside initiatives.

    RESULTS: Multiple interventions over the years have increased international nonproprietary name prescribing (99% for statins) and preferential prescribing of generic versus patented statins, and reduced inappropriate prescribing of ezetimibe. This resulted in a 50% reduction in expenditure of LLAs between 2001 and 2015 despite a 412% increase in utilization, increased prescribing of higher dose statins (71% in 2015) especially atorvastatin following generic availability, and reduced prescribing of ezetimibe (reduced by 72% between 2010 and 2015). As a result, the quality of prescribing has improved.

    CONCLUSION: Generic availability coupled with multiple measures has resulted in appreciable shifts in statin prescribing behavior and reduced ezetimibe prescribing, resulting in improvements in both the quality and efficiency of prescribing.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage*; Hydroxymethylglutaryl-CoA Reductase Inhibitors/economics
  10. Faseleh Jahromi M, Liang JB, Ho YW, Mohamad R, Goh YM, Shokryazdan P, et al.
    Biomed Res Int, 2013;2013:604721.
    PMID: 23710454 DOI: 10.1155/2013/604721
    Lovastatin, a natural byproduct of some fungi, is able to inhibit HMG-CoA (3-hydroxy-3 methyl glutaryl CoA) reductase. This is a key enzyme involved in isoprenoid synthesis and essential for cell membrane formation in methanogenic Archaea. In this paper, experiments were designed to test the hypothesis that lovastatin secreted by Aspergillus terreus in fermented rice straw extracts (FRSE) can inhibit growth and CH4 production in Methanobrevibacter smithii (a test methanogen). By HPLC analysis, 75% of the total lovastatin in FRSE was in the active hydroxyacid form, and in vitro studies confirmed that this had a stronger effect in reducing both growth and CH4 production in M. smithii compared to commercial lovastatin. Transmission electron micrographs revealed distorted morphological divisions of lovastatin- and FRSE-treated M. smithii cells, supporting its role in blocking normal cell membrane synthesis. Real-time PCR confirmed that both commercial lovastatin and FRSE increased (P < 0.01) the expression of HMG-CoA reductase gene (hmg). In addition, expressions of other gene transcripts in M. smithii. with a key involvement in methanogenesis were also affected. Experimental confirmation that CH4 production is inhibited by lovastatin in A. terreus-fermented rice straw paves the way for its evaluation as a feed additive for mitigating CH4 production in ruminants.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
  11. Hassan Y, Al-Jabi SW, Aziz NA, Looi I, Zyoud SH
    Clin Neuropharmacol, 2011 Nov-Dec;34(6):234-40.
    PMID: 21996648 DOI: 10.1097/WNF.0b013e3182348abe
    BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs), antiplatelets (APs), and statin are increasingly being prescribed for ischemic stroke prevention.
    OBJECTIVES: The objective of the study was to examine whether previous combination therapy of ACEI with AP and/or statin has additive effect compared with ACEI alone on functional outcome after ischemic stroke. Furthermore, factors associated with improving functional outcome were investigated.
    METHODS: Ischemic stroke patients attending a Malaysian hospital in 2008 were categorized according to Barthel Index at discharge. Favorable outcome was defined as Barthel Index of 75 or greater. Data included demographic information, clinical characteristics, and previous medications with particular attention to ACEI, AP, and statin.
    RESULTS: Overall, 505 patients were included. Variables associated with good functional outcome were younger age (P = 0.002), first-ever attack (P = 0.016), lacunar (P = 0.015) or posterior circulation infarct stroke subtype (P = 0.034), minor Glasgow Coma Scale (P < 0.001), and previous use of ACEI alone or combined with AP and/or statin (P = 0.002). Using ACEI alone as the reference for ACEI + AP, ACEI + statin, or ACEI + AP + statin combinations, there was no significant difference among combinations on improving functional outcome (P = 0.852).
    CONCLUSIONS: Prestroke use of ACEI either alone or combined with AP and/or statin was associated with better functional outcome. Previous use of ACEI in combination with AP and/or statin did not significantly differ from ACEI alone in their effect on outcome. Our study provides a potential rationale for optimizing the use of ACEI among individuals at risk of developing ischemic stroke.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage*
  12. Hassan Y, Kassab Y, Abd Aziz N, Akram H, Ismail O
    J Clin Pharm Ther, 2013 Apr;38(2):97-100.
    PMID: 23441979 DOI: 10.1111/jcpt.12027
    Pharmacists have the knowledge regarding optimal use of medications and the ability to influence physician prescribing. Successful interventions by a pharmacist to implement cardioprotective medications to a coronary artery disease patient's regimen would not only improve the patient's quality of care but may also increase his or her likelihood of survival. Therefore, the aim of this study was to (i) evaluate the effectiveness of pharmacist initiated interventions in increasing the prescription rates of acute coronary syndrome (ACS) secondary prevention pharmacotherapy at discharge, and to (ii) evaluate the acceptance rate of these interventions by prescribers.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  13. Hammad MA, Syed Sulaiman SA, Alghamdi S, Mangi AA, Aziz NA, Mohamed Noor DA
    Diabetes Metab Syndr, 2020 04 09;14(4):341-346.
    PMID: 32305775 DOI: 10.1016/j.dsx.2020.04.005
    BACKGROUND: Peripheral neuropathy (PN) is a complaint with often unidentified reasons. Some medicines, including statins therapy, are anticipated to be amongst the reasons for PN.

    AIMS: This study intended to assess the association of peripheral neuropathy with statins therapy amongst Type 2 diabetic patients.

    METHODS: At Penang General Hospital, 757 cases were categorized into two groups (564 with statins therapy and 193 without statins therapy). The diagnosis of PN was investigated retrospectively for a period of 10 years (2006-2016). Confounding risk factors as age, diabetes period, hypertension, glycemic control, other co-morbidity, and prescriptions were matched.

    RESULTS: About 129 (22.9%) cases from 564 statins users had PN. Only 30 (15.5%) subjects had PN from 193 statins non-users. Chi-square test showed a significant variance among statins treatment cohort and statin-free cohort in the occurrence of PN (P-value: 0.001). Spearman's investigation presented a positive correlation (r: 0.078, p-value: 0.031) among statins use and PN prevalence. Binary logistic regression was statistically significant for statins therapy as a predictor of peripheral neuropathy incidence (r2: 0.006, p-value: 0.027) amid diabetic patients. The relative risk of peripheral neuropathy connected with statins therapy is (RR: 1.47, 95% CI: 1.02-2.11). The excess relative risk is 47.1%. While the absolute risk (AR) is 7.3% and the number needed to harm (NNH) is 14.

    CONCLUSIONS: The study indicated a positive association between peripheral neuropathy and statins utilization. Peripheral neuropathy was higher amongst statins users than the statins-free group.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects*
  14. Lee CY, Liu KT, Lu HT, Mohd Ali R, Fong AYY, Wan Ahmad WA
    PLoS One, 2021;16(2):e0246474.
    PMID: 33556136 DOI: 10.1371/journal.pone.0246474
    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.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  15. Hammad MA, Syed Sulaiman SA, Aziz NA, Mohamed Noor DA
    Diabetes Metab Syndr, 2019 04 12;13(3):1797-1803.
    PMID: 31235097 DOI: 10.1016/j.dsx.2019.04.006
    AIMS: The study was intended to evaluate the association of cognitive impairment with statins therapy among diabetic outpatients.

    METHODS: Mini-Addenbrooke's Cognitive Examination (M-ACE) was conducted for 280 cases in a cross-sectional study at Hospital Pulau Pinang. M-ACE score is 30, and the cut-off score for mild cognitive impairment is ≤ 21 and ≤ 16 for dementia.

    RESULTS: The cognitive impairment was distributed among 59 (55.1%) patients with mild cognitive impairment and 48 (44.9%) patients with dementia. From 177 patients using statins, about 80 (45.2%) cases had cognitive impairment. While from 103 statins non-users, only 27 (26.2%) had cognitive impairment. The relative risk of cognitive impairment associated with statins use in diabetic patients is (RR: 1.72, 95% CI: 1.2-2.48) and the excess relative risk is 72.4%. The absolute risk is 19%, and the number needed to harm is 6. Spearman's test indicated a positive association between statins usage and cognitive impairment incidence (r: 0.188, p-value: 0.002). However, Spearman's test showed a non-significant correlation amongst statins and dementia incidence (P-value: 0.587, RR: 1.16, 95% CI: 0.67-2.02).

    CONCLUSIONS: Statins therapy has a higher association with cognitive impairment risk than statins-free treatment; however, there is no association between statin use and dementia incidence among diabetic patients.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects*
  16. EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
    Lancet, 2021 11 06;398(10312):1713-1725.
    PMID: 34506743 DOI: 10.1016/S0140-6736(21)01122-3
    BACKGROUND: The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.

    METHODS: Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.

    FINDINGS: Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3-58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5-56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32-6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20-5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001).

    INTERPRETATION: Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia.

    FUNDING: Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
  17. Khatib R, McKee M, Shannon H, Chow C, Rangarajan S, Teo K, et al.
    Lancet, 2016 Jan 2;387(10013):61-9.
    PMID: 26498706 DOI: 10.1016/S0140-6736(15)00469-9
    BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability.
    METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry.
    FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55).
    INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025.
    FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors/economics; Hydroxymethylglutaryl-CoA Reductase Inhibitors/supply & distribution; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  18. Chaiyasothi T, Nathisuwan S, Dilokthornsakul P, Vathesatogkit P, Thakkinstian A, Reid C, et al.
    Front Pharmacol, 2019;10:547.
    PMID: 31191304 DOI: 10.3389/fphar.2019.00547
    Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients. Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes. Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72-0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65-0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75-0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST. Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients.
    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors
  19. Kongpakwattana K, Ademi Z, Chaiyasothi T, Nathisuwan S, Zomer E, Liew D, et al.
    Pharmacoeconomics, 2019 Oct;37(10):1277-1286.
    PMID: 31243736 DOI: 10.1007/s40273-019-00820-6
    BACKGROUND: Using non-statin lipid-modifying agents in combination with statin therapy provides additional benefits for cardiovascular disease (CVD) risk reduction, but their value for money has only been evaluated in high-income countries (HICs). Furthermore, studies mainly derive effectiveness data from a single trial or older meta-analyses.

    OBJECTIVES: Our study used data from the most recent network meta-analysis (NMA) and local parameters to assess the cost effectiveness of non-statin agents in statin-treated patients with a history of CVD.

    METHODS: A published Markov model was adopted to investigate lifetime outcomes: (1) number of recurrent CVD events prevented, (2) quality-adjusted life-years (QALYs) gained, (3) costs and (4) incremental cost-effectiveness ratios (ICERs) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and ezetimibe added to statin therapy. Event rates and effectiveness inputs were obtained from the NMA. Cost and utility data were gathered from published studies conducted in Thailand. A series of sensitivity analyses were performed.

    RESULTS: Patients receiving PCSK9i and ezetimibe experienced fewer recurrent CVD events (number needed to treat [NNT] 17 and 30) and more QALYs (0.168 and 0.096 QALYs gained per person). However, under the societal perspective and at current acquisition costs in 2018, ICERs of both agents were $US1,223,995 and 27,361 per QALY gained, respectively. Based on threshold analyses, the costs need to be reduced by 97 and 85%, respectively, for PCSK9i and ezetimibe to be cost-effective.

    CONCLUSIONS: Despite the proven effectiveness of PCSK9i and ezetimibe, the costs of these agents need to reduce to a much greater extent than in HICs to be cost-effective in Thailand.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors
  20. Darrat M, Flaherty GT
    PMID: 31548898 DOI: 10.1186/s40794-019-0094-8
    Background: Older people represent a significant proportion of overseas travellers. The epidemiology of older international travellers is not well described in the literature. This study aims to identify demographics, travel characteristics and the medical profile of older travellers seeking pre-travel health advice in a specialist travel medicine clinic.

    Methods: Records of travellers aged 60 years and older attending the Tropical Medical Bureau clinic in Galway, Ireland between 2014 and 2018 were examined. Descriptive and inferential.analysis of data was performed.

    Results: A total of 337 older travellers sought pre-travel health advice during the study period. The mean age of the cohort was 65.42 (±10) years. Most of the travellers (n = 267, 80%) had at least one travelling companion. Nearly half of older travellers (n = 155, 46.8%) were travelling with a single companion. Tourism was the main reason for travel for the majority (n = 260, 77.6%), followed by visiting friends and relatives (VFR) (n = 23, 6.9%) travellers. The mean interval remaining before the planned trip was 4.36 (±2) weeks, and the mean duration of travel was 3.16 (±1) weeks. The most popular single country of destination was India with 33 (9.8%) visitors, and South East Asia was the most popular region with 132 (39.2%) older travellers. The majority of travellers (n = 267, 79.2%) had a documented pre-existing medical condition. The most commonly reported medical conditions were hypertension (n = 26, 7.7%), dyslipidaemia (n = 18, 5.3%), diabetes mellitus (n = 12, 3.5%), insect bite sensitivity (n = 11, 3.3%), and hypothyroidism (n = 9, 2.6%). Antihypertensive agents (n = 32, 9.4%) and statins (n = 24, 7.1%) were the most frequently used medications. Typhoid (n = 112, 33.2%) and hepatitis A (n = 84, 24.9%) were the most common vaccinations administered to older travellers at the clinic.

    Conclusions: This study provides an insight into the demographics, travel characteristics, and medical profile of elderly travellers seeking advice at a large travel clinic in Ireland. A wide range of travel destinations, diseases and medication use was reported among this group of travellers, which may enable travel medicine physicians to provide more tailored advice and to more appropriately counsel older travellers.

    Matched MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors
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